PHARMACOLOGY

CANCER PHARMCOTHERAPY

The objective of cancer pharmacotherapy is bowel movement, and interferences in

to: the sense of taste and a decline in
● cure cancer using cancer overall Immunity.
pharmacotherapy, for example in the
case of testicular cancer and HORMONAL THERAPY
lymphomas The hormonal therapy of cancer aims to
● prevent the recurrence of cancer as a prevent the production of the hormone vital to
post-operative treatment, i.e. as the cancer in question and its effects on the
adjuvant therapy, for example after body.
breast cancer or intestinal cancer
surgery What Is This Topic About?
● Relieve symptoms caused by cancer Pt. receiving hormonal therapy
and extend life expectancy in the ● i.e. female hormone among women
treatment of advanced cancer. cause menopausal symptoms due to the
shortage of the female hormone
Medication impact mechanism:  ● Hormonal therapy can be implemented
 Chemotherapy either as tablets or injections
 Hormonal therapies ● Long term therapy
 Hormonal therapies
 Targeted drugs Targeted drugs
 Immunologic drugs ● Targeted drugs are used, among other
things, in the treatment of certain blood
Chemotherapy cancer, lung cancer, breast cancer,
• Chemotherapy have an effect by lymphatic tissue cancer, renal cancer,
preventing the division of all cells, liver cancer and intestinal cancer types.
which often leads to the death of cancer
cells.  Immunologic drugs
• Cancer cells are particularly sensitive to DISADVANTAGE
cytostatics, because they divide faster ●  Aim to boost the immune system of the
than normal cells.  body and so cause the body’s own
• Testicular cancer and lymphomas are immune defense system to attack the
particularly sensitive to chemotherapy. cancer cells.
• Chemotherapy is usually administered CAREFUL
intravenously or orally as tablets. In ● The disadvantage of treatments based
some cases, they can be administered on immune defense is that, once you
locally, for example, into the spinal interfere with the body’s defense
canal. mechanisms, the body may also attack
• The most common side effects include its own tissue and cause autoimmune
nausea, hair loss, fatigue, problems with diseases and severe inflammation
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General Principles in the Pharmacotherapy These agents are most effective on cells
of Cancer Anton Wellstein entering mitosis, the most vulnerable phase of
the cell cycle.
THE CELL CYCLE CANCER EVOLUTION
AND DRUG DISCOVERY DRUG • A phase that precedes DNA synthesis (G1)
RESISTANCE MOLECULAR TESTING TO • A DNA synthesis phase (S)
SELECT APPROPRIATE DRUGS • An interval following the termination of DNA
■ Molecular Analysis and Tumor synthesis (G2)
Heterogeneity • The mitotic phase (M) in which the cell,
■ Liquid Biopsies containing a double complement of DNA,
divides into two daughter G1, cells
ACHIEVING THERAPEUTIC • A probability of moving into a quiescent state
INTEGRATION AND EFFICACY A (G0) and failing to move forward for long
CAUTIONARY NOTE periods of time.
Cancer pharmacology has changed
dramatically during the recent past with the The CDK family consists of over 20
improved understanding of cancer biology and serine/threonine protein kinases that have been
an ever-expanding set of newly developed amongst the first pathway targets pursued for
drugs that target vulnerabilities in individual the treatment of cancer. However, different
cancers. Effective early treatments have been tissue selectivities and distinct cell cycle
developed for some fatal malignancies, specific activity periods of the various CDKs
including testicular cancer, lymphomas, and provide a challenge for the development of
leukemia. Also, adjuvant chemotherapy and CDK inhibitors. CDK4/6 have become
hormonal therapy can extend over-all survival attractive targets because they control cell
and prevent disease recurrence following cycle progression from the G1 to the S phase.
surgical resection of localized breast, Interaction of cyclin D with CDK4/6 enhances
colorectal, and lung cancers. Chemotherapy is phosphorylation and inactivation of the
also employed as part of the multimodal retinoblastoma (Rb) protein, followed by the
treatment of locally advanced head and neck, transcription of factors that control transition
breast, lung, and esophageal cancers; soft tissue into the S phase. CDK4/6 inhibition will thus
sarcomas; and pediatric solid tumors, thereby cause a G1 arrest in susceptible cells that
allowing for surgery that is more limited with utilize this pathway.
favourable outcomes.
The Cell Cycle An understanding of the cell The CDK4/6 inhibitor palbociclib was recently
cycle is essential for the rational use of anti- approved for the treatment of breast cancer.
cancer drugs. Many cytotoxic agents act by Cancer Evolution and Drug Discovery The
damaging. DNA. Their toxicity is greatest rapidly expanding knowledge of cancer biology
during S phase, the DNA synthetic phase of the and the ability to analyse cancer genome
cell cycle. Other agents, such as the vinca alterations in thousands of patient samples have
alkaloids and taxanes, block the formation of a led to a better understanding of the molecular
functional mitotic spindle in the M phase. evolution of cancer and the discovery of
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cancer-specific drug targets: growth factor subpopulations are selected based on their
receptors, intracellular signalling pathways, growth capacity, adaptation to the tumor
epigenetic processes, Tumor vascularity, DNA microenvironment at the primary or metastatic
repair defects, cell death pathways, and site, and the evasion of immune surveillance.
immune escape mechanisms (Hanahan and Drug treatment will add evolutionary pressure
Weinberg, 2011). Human malignancies are a and select for resistant subpopulations.
highly diverse Differently colored dots indicate tumor
subpopulations of different genetic makeup.
Clinically detectable cancer lesions represent
approximately 1 g of tumor tissue or 109 cells B. Mutational load. Data are median number
and can contain a multitude of subpopulations of somatic mutations per million bases plus or
and a wide variety of genetic alterations. The minus the range observed for some major
dynamic evolution of individual cancer human cancers. Note that the ordinate is a
genomes and the implications for the logarithmic scale. In 7042 cancer specimens
development of therapies was established from between 100 and 1,000,000 mutations were
the analyses of specimens from diverse detected per tumor specimen, with a 30 to 1000
cancers. This dynamic was exemplified in a fold range amongst individual specimens from
detailed analysis of a series of multiple parallel a single cancer type. A typical mutation burden
biopsies from different sites in patients with of 10 somatic mutations per megabase (=
metastatic melanoma during treatment with 30,000 per genome of 3 × 109 base pairs)
inhibitors of BRAF. The genomic analysis of results in approximately 150 mutations in
the biopsies revealed complex and distinct amino acid sequences that can alter protein
evolutionary branching architectures due to the function, drug sensitivity, and antigenicity.
selection of drug resistant subpopulations Such data have been analysed in terms of the
during treatment likelihood of formation of specific neoantigens
that permit the immune system to distinguish
These examples emphasize that new strategies between tumor and normal cells and are
for drug discovery and development, and putative factors of importance in cancer
advances in patient care, will result from new immunotherapy. (Schumacher and Schreiber,
knowledge of cancer biology. One response to 2015). Adeno, adenocarcinoma; SCC,
the oncogene addiction paradigm has been to squamous cell carcinoma; SCLC, small cell
group cancers by shared vulnerabilities and lung cancer.
include patients in so-called basket trials that
evaluate a drug based on its target rather than Drug Resistance remains the major obstacle to
particular disease entities and consider successful cancer treatment. Resistance results
sensitivity and resistance to treatments in that from a variety of molecular changes that can
context. However, in the foreseeable future, defeat the best-designed treatments.
targeted drugs and cytotoxics will continue to Mechanisms of drug resistance include poor
be used in combination. drug absorption and delivery; genetically
determined variability in drug transport,
A. Treatment resistance. Cancers accumulate activation, and clearance; and mutations,
mutations during their evolution. Cancer cell amplifications, or deletions in drug targets
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(Holohan et al., 2013). The resistance process blood samples from patients with cancer
is best understood for pathway targeted drugs. (“liquid biopsies”) and to follow changes in the
abundance of mutant KRAS during colon
Molecular Testing to Select Appropriate cancer treatment (Diehl et al., 2008). The
Drugs Clinical trials and patient treatments analysis of ctDNA has also shown that during
increasingly employ results from biomarker antiestrogen therapy of breast cancer the
analysis to identify patients likely to benefit appearance of mutant estrogen receptor
from particular treatments and individuals at coincides with subsequent resistance to
the greatest risk of toxicity. Some of the tests. aromatase inhibitor treatment
Have been approved by the FDA as
“companion diagnostics” in conjunction with Achieving Therapeutic Integration and
specific drug therapies. Pre-treatment testing of Efficacy The clinical benefit of cytotoxic drugs
tumor specimens is standard practice in has primarily been measured by radiological
selecting patients for antihormonal therapy of assessment of drug effects on tumor size.
breast cancer and for treatment with antibodies Pathway-targeted agents, however, may slow
such as trastuzumab (anti-HER2). or halt tumor growth, so their effects may be
Inherited differences in protein sequence measured in the assessment of time to disease
polymorphisms or levels of RNA expression progression; however, for some immune
can also influence toxicity and antitumor checkpoint inhibitors, tumor lesions may
response. For example, tandem repeats in the initially increase in size due to cytotoxic
promoter region of the gene encoding lymphocyte infiltration.
thymidylate synthase, the target of 5-
fluorouracil, determine the level of expression A Cautionary Note Although advances in drug
of the enzyme. discovery and molecular profiling of tumors
offer great promise for improving the outcomes
Molecular Analysis and Tumor of cancer treatment, a final word of caution
Heterogeneity regarding all treatment regimen deserves
One of the caveats to conclusions drawn from emphasis: The pharmacokinetics and toxicities
the molecular analysis of tumor specimens is of cancer drugs vary amongst individual
the dynamic evolution of cancers outlined patients. It is imperative to recognize toxicities
previously. Clinically important mutations in early, to alter doses or discontinue offending
subclones may be missed due to geographically medication to relieve symptoms and reduce
inadequate sampling and may provide the risk, and to provide vigorous supportive care.
wrong guidance to treatment decisions.
Response to treatment of different CELL CYCLE-NON SPECIFIC AND
subpopulations presents a further challenge and SPEFICIC ANTICANCER DRUGS
would require multiple-site, longitudinal A cell cycle is a series of events that takes
sampling (Shi et al., 2014). place in a cell as it grows and divides. A cell
spends most of its time in what is called
Liquid Biopsies interphase, and during this time it grows,
More recent technology advances have made it replicates its chromosomes, and prepares for
possible to measure circulating, ctDNA in cell division. The cell then leaves interphase,
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undergoes mitosis, and completes its division. Double time- is defined as the time it takes for
The resulting cells, known as daughter cells, a tumor to double in size
each enter their own interphase and begin a What you need to know…
new round of the cell cycle.  Anti-cancer drugs are more effective
against neoplastic cells that have a high
Cell cycle G1 phase (post mitotic gap) - growth fraction
Production of RNA, protein, and enzymes for  Solid tumors have a large percentage of
DNA synthesis. It lasts 15 to 18 hours their cell mass in the G0 phase , thus
S phase (synthesis) - all components are they generally have a low growth
synthesized and the cells have doubled. It fraction sensitive to anticancer drugs
lasted 10 to 20 hours  High dose chemotherapy results in
G2 phase (premitotic gap) - the cell continues better tumor-killing effects
to grow and ensures it is not defective; lasted  Adequate vascularization is needed for
approx. 3 hours the anticancer drugs to be effective
M phase (mitosis) - cell growth has stopped,  Anticancer drugs are more effective
and the cell divides into 2 identical (daughter against small, fast-growing tumors with
cells); lasted approx. 1 hour sufficient blood supply
G0 phase (resting)- cells remain in the phase  Solid tumors can be inconsistent
and leave the cell cycle or return to the cell  Some areas of tumor may have an
cycle for cell replication. Cells in this phase are adequate blood supply, whereas other
not as sensitive to many antineoplastic drugs areas are poorly perfused
Defective cells undergo apoptosis
CYTOTOXIC DRUGS
Cell cycle-nonspecific and cell cycle specific • (Sometimes known as antineoplastic)
anticancer drugs describe a group of medicines that
CCNS contain chemicals which are toxic to
 Drugs acts during any phase of the cell cells, preventing their replication or
cycle, including G0 phase growth, and so are used to treat cancer.
 Includes most alkylating drugs,
antitumor, antibiotics, and hormones ALKYLATING DRUGS
CCS ➜ One of the largest groups of anticancer
• Drugs exert their influence during a drugs.
specific phase of the cell cycle and are ➜ It damage the cell’s DNA by cross-
most effective against rapidly growing linkage of DNA strands, abnormal base
cancer cells pairing, or DNA strand breaks, thus
• Include antimetabolites, some preventing the reproduction of cancer
alkylating agents and vinca alkaloids cells.
➜ They are used to treat many different
Growth fraction- the percent of actively
types of cancer including leukemia,
dividing cells, decreases as the tumor enlarges,
lymphoma, multiple myeloma,
and double time increases
sarcoma, and solid tumors such as those

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 of the breast, ovary, uterus, lungs, Hodgkin disease and
bladder, and stomach. non-Hodgkin
lymphoma (NHL),
5 CLASSES OF ALKYLATING DRUGS acute and chronic
1 nitrogen mustards lymphocytic leukemia
2 nitrosoureas (CLL) and etc.
3 alkyl sulfonate
Used for immunologic
4 triazines disorders such as
5 ethylenimines lupus nephritis, and
has been shown to
NITROGEN MUSTARDS prevent progressive
➜ Were produced in 1920s and 1930s as renal scarring,
potential chemical warfare weapons. preserve renal
They are vesicants (or blister agents) function, induce renal
similar to the sulfur mustards remission and
➜ Not found naturally in the environment decrease end-stage
➜ HN-1 originally was designed to renal failure.
remove warts but later on, it was IFOSFAMIDE ADME
identified as a potential chemical Ifosfamide has a
warfare agent. plasma elimination t
1/2 is 1.5 h after doses
➜ HN-2 was designed for military agent
of 3.8–5 g/m2 and a
but was later used in cancer treatment.
somewhat shorter t 1/2
at lower doses; its
NITROGEN MUSTARDS
pharmacokinetics are
MECHLORETHA The first clinically highly variable due to
MINE used nitrogen mustard variable rates of
and is the most hepatic metabolism
reactive of the drugs
in this class. It is used Therapeutic Uses:
topically for treatment For treatment of
of CTCL as a solution patients with relapsed
that is rapidly mixed germ cell testicular
and applied to affected cancer and is
areas. It has been frequently used for
largely replaced by first-time treatment of
cyclophosphamide, pediatric or adult
melphalan, and other patients with
more stable alkylating sarcomas. It is a
agents. common component
CYCLOPHOSPHA An analogue of of high dose
MIDE nitrogen mustard and chemotherapy
has activity against regimens with bone
many neoplastic marrow or stem cell
diseases such as
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 rescue. Treatment is repeated
at 4-week intervals
Adverse Effects based on response and
Ifosfamide has a tolerance.
similar toxicity profile
as cyclophosphamide, Nausea and vomiting
although it causes are less frequent. The
greater platelet drug causes less
suppression, alopecia and, rarely,
neurotoxicity, renal or hepatic
nephrotoxicity, and dysfunction.
urothelial damage. CHLORAMBUCIL ADME:
Oral absorption of
MELPHALAN ADME: chlorambucil is
- - given as an adequate and reliable.
intravenous infusion. The drug has a t 1/2 in
The drug has a plasma plasma of about 1.5 h
t 1/2 of about 45–90 and is hydrolyzed to
min; 10%–15% of an inactive products.
administered dose is
excreted unchanged in Therapeutic Uses
the urine. Patients and Adverse Effects:
with decreased renal Chlorambucil is
function may develop almost exclusively
unexpectedly severe used in treating CLL.
myelosuppression. In treating CLL,
chlorambucil is given
Therapeutic Uses once daily and
and Adverse Effects: continued for 3–6
The alkylating agent weeks. Chlorambucil
melphalan primarily is treatment may
used to treat multiple continue for months or
myeloma and, less years, achieving its
commonly, in high- effects gradually and
dose chemotherapy often without
with marrow significant toxicity to
transplantation. a compromised bone
marrow.
Melphalan for
multiple myeloma is Marked hypoplasia of
administered orally the bone marrow may
for 4–7 days every 28 be induced with
days, with excessive doses, but
dexamethasone or the myelosuppressive
thalidomide. effects are moderate,

7
 gradual, and rapidly divided doses
reversible. GI
discomfort, Adverse Effect:
azoospermia, Gynecomastia and
amenorrhea, impotence may occur.
pulmonary fibrosis,
seizures, dermatitis, NITROSOUREAS
and hepatotoxicity ➜ an important role in the treatment of brain
rarely may be tumors and find occasional use in treating
encountered. lymphomas and in high-dose regimens with
BENDAMUSTINE ➜ Bendamustine bone marrow reconstitution
is approved for
➜ The use of nitrosoureas is presently limited
treatment of
to brain tumors due to their Lipophilicity
CLL and non-
Hodgkin
lymphoma. NITROSOUREAS
➜ Bendamustine CARMUSTIN ADME:
is given as a E (BNCU) Carmustine is unstable in
30-min aqueous solution and in
intravenous body fluids. After
infusion on intravenous infusion, it
days 1 and 2 of disappears from the
a 28-day cycle. plasma with a highly
Lower doses variable t 1/2 of 15–90
may be min or more.
indicated in Approximately 30%–80%
heavily of the drug appears in the
pretreated urine within 24 h as
patients degradation products
➜ The parent Therapeutic Uses:
drug has a Carmustine (BCNU) is
plasma t 1/2 of administered
about 30 min intravenously over 1–2 h
ESTRAMUSTINE ADME: and repeated every 6
The drug has a plasma weeks. Because of its
t 1/2 of about 20-24 h. ability to cross the blood-
brain barrier, carmustine
Therapeutic Effect: has been used in the
Estramustine is treatment of malignant
approved for gliomas. An implantable
treatment prostate carmustine wafer is
cancer. available for use as an
adjunct to surgery for
Estramustine is given
recurrent glioblastoma
as orally in 3-4
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 multiforme.
➜ Approved for ALKYL
treatment of SULFONATE
Hodgkin disease ADME
and malignant Busulfan is well
LOMUSTINE glioma. absorbed after oral
(CCNU) ➜ given as orally for administration and has
every 6 weeks a plasma t 1/2 of 2–3 h.
➜ The drug has a
Therapeutic Uses :
plasma t 1/2 of
In treating CML, the
about 16 h- 2 days.
initial oral dose of
ADME :
busulfan varies with the
Streptozocin is rapidly
total leukocyte count
degraded following
and the severity of the
intravenous
disease; daily doses are
administration. The t 1/2
adjusted to subsequent
of the drug is about 15
hematological and
min. Only 10%–20% of a
clinical responses, with
dose is recovered intact in
the aim of reducing the
the urine BUSULFAN
total leukocyte count to
Therapeutic Uses: 10,000 cells/mm3 or
Used in the treatment of less.
human pancreatic islet cell
Adverse Effects:
carcinoma and carcinoid
The toxic effects of
tumors. It is administered
busulfan are related to
intravenously once daily
its myelosuppressive
STREPTOZO for 5 days; this course is
properties; prolonged
CIN repeated every 6 weeks
thrombocytopenia may
Adverse Effects: occur. Occasionally,
Nausea is frequent. Mild, patients experience
reversible renal or hepatic nausea, vomiting, and
toxicity occurs in diarrhea. Long-term
approximately two-thirds use leads to impotence,
of cases; in fewer than sterility, amenorrhea,
10% of patients, renal and fetal malformation.
toxicity may be
cumulative with each dose TRIAZINES
and may lead to DACARBAZINE ADME :
irreversible renal failure. (DTIC) Dacarbazine is
Hematological toxicities administered
(anemia, leukopenia, and intravenously. After an
thrombocytopenia) occur initial rapid phase (t 1/2
in 20% of patients. of about 20 min),
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dacarbazine is cleared ADME:
from plasma with a Temozolomide is
terminal t 1/2 of about 5 administered orally and
h. The t 1/2 is prolonged has a bioavailability
in the presence of hepatic approaching 100%.
or renal disease. Almost Plasma levels of the
50% of the compound is parent drug decline with a
excreted intact in the t 1/2 of 1–2 h. The
urine by tubular secretion. primary active metabolite
MTIC reaches a
Therapeutic Uses : maximum plasma
The primary clinical concentration (150
indication for dacarbazine mg/mL) 90 min after a
is in the chemotherapy of dose and declines with a t
Hodgkin disease. In 1/2 of 2 h.
TEMOZOLOMI
combination with other
DE
drugs for Hodgkin Therapeutic Uses:
disease, It is given on day Temozolomide is the
1 and 15 and repeated standard agent, in
every 4 weeks for up to 6 combination with
cycles. It is modestly radiation therapy, for
effective against patients with malignant
malignant melanoma and glioma and astrocytoma.
adult sarcomas. For
malignant melanoma is Adverse Effects:
given for a 10-day period, The toxicities of
repeated every 28 days; temozolomide mirror
alternatively, it can be those of DTIC.
given daily for 5 days and Hematological monitoring
repeated every 3 weeks. is necessary to guide
dosing adjustments.
Adverse Effects:
Dacarbazine induces ETHYLENIMINES
nausea and vomiting in ALTRETAM ADME:
more than 90% of INE Altretamine is well absorbed
patients; vomiting usually from the GI tract; its
develops 1–3 h after elimination t 1/2 is 4–10 h.
treatment and may last up The drug undergoes rapid
to 12 h. demethylation in the liver
Myelosuppression, with
both leukopenia and Adverse Effects:
thrombocytopenia, is mild The main toxicities of
and readily reversible altretamine are
within 1–2 weeks. A flu- myelosuppression and
like syndrome may occur. neurotoxicity. Altretamine
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 causes both peripheral and intermediates like other alkylating agents or
central neurotoxicity (ataxia, formally alkylate DNA, they covalently bind to
depression, confusion, nucleophilic sites on DNA and share many
drowsiness, hallucinations, pharmacological attributes with alkylators.
dizziness, and vertigo).
PLATINUM COORDINATION
ADME:
COMPLEXES
Within hours of thiotepa
CISPLATIN Therapeutic Uses:
administration, TEPA
Cisplatin, in combination
becomes the predominant
with bleomycin, etoposide, or
form of the drug present in
with ifosfamide and
plasma. The parent
vinblastine, cures 90% of
compound has a plasma t 1/2
patients with testicular
of 1.2–2 h; TEPA has a
cancer. Used with paclitaxel,
longer t 1/2, 3–24 h. Thiotepa
cisplatin or carboplatin
pharmacokinetics essentially
induces complete response in
are the same in children as in
the majority of patients with
adults at conventional doses
carcinoma of the ovary.
(≤80 mg/m2), and drug and
Cisplatin produces responses
metabolite t 1/2 are
in cancers of the bladder,
unchanged in children
THIOTEPA head and neck, cervix, and
receiving high-dose therapy
endometrium. The drug also
of 300 mg/m2 /d for 3 days.
sensitizes cells to radiation
therapy and enhances control
Adverse Effects:
of locally advanced lung,
Toxicities include
esophageal, and head and
myelosuppression and, to a
neck tumors when given with
lesser extent, mucositis.
irradiation.
Myelosuppression tends to
develop somewhat later than
Adverse Effects:
with cyclophosphamide, with
leukopenic nadirs at 2 weeks ➜ nephrotoxicity
and platelet nadirs at 3 weeks. ➜ Ototoxicity
In high doses, thiotepa may ➜ progressive peripheral
cause neurotoxic symptoms, motor and sensory
including coma and seizures neuropathy
➜ mild-to-moderate
PLATINUM COORDINATION myelosuppression
COMPLEXES ➜ Anemia may become
Platinum coordination complexes have broad prominent after
antineoplastic activity and have become the multiple cycles of
foundation for treatment of ovarian, head and treatment
neck, bladder, esophagus, lung, and colon ➜ Electrolyte
cancers. Although cisplatin and other platinum disturbances
complexes do not form carbonium ion ➜ Anaphylactic-like
11
 reactions, less nausea, neurotoxicity,
characterized by facial ototoxicity, and
edema, nephrotoxicity than cisplatin.
bronchoconstriction, The dose-limiting toxicity of
tachycardia, and carboplatin is
hypotension myelosuppression, primarily
➜ Development of thrombocytopenia. It may
AML, usually 4 years cause a hypersensitivity
or more after reaction; in patients with a
treatment. mild reaction, premedication,
CARBOPL ADME: graded doses of drug, and
ATIN the majority of drug in more prolonged infusion lead
plasma remains in its parent to desensitization.
form, unbound to proteins. OXALIPLA ADME:
Most drug is eliminated via TIN Oxaliplatin has a short t 1/2
renal excretion, with a t 1/2 of in plasma, probably as a
about 2 h result of its rapid uptake by
tissues and its reactivity; the
Therapeutic Uses initial t 1/2 is about 17 min.
Carboplatin and cisplatin are No dose adjustment is
equally effective in the required for hepatic
treatment of patients with dysfunction or for patients
suboptimally debulked with a CLCr ≥ 20 mL/min.
ovarian cancer, NSCLC, and
SCLC; Carboplatin, on the Therapeutic Uses:
other hand, may be less Oxaliplatin exhibits a range
effective than cisplatin in the of antitumor activity
treatment of germ cell, head (colorectal and gastric cancer)
and neck, and esophageal that differs from other
cancers. Carboplatin is an platinum agents. Oxaliplatin’s
effective alternative for effectiveness in colorectal
patients who cannot tolerate cancer is perhaps due to its
cisplatin due to impaired MMR- and HMG-
renal function, refractory independent effects. In
nausea, or neuropathy, but combination with 5FU, it is
doses must be adjusted for approved for treatment of
renal function. Carboplatin is patients with colorectal
administered as an cancer.
intravenous infusion over at
least 15 min and is given Adverse Effects:
once every 21–28 days. ➜ The dose-limiting
toxicity of oxaliplatin
Adverse Effects: is peripheral
Carboplatin is relatively well neuropathy.
tolerated clinically, causing ➜ An acute form, often
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 triggered by exposure N5–10 methylene FH4 and N10 formyl FH4
to cold liquids, cofactors that are required for the synthesis of
manifests as thymidylate and purines. In addition, MTX,
paresthesias or like cellular folates, undergoes addition of a
dysesthesias in the series of polyglutamates (MTX-PGs) in both
upper and lower normal and tumor cells
extremities, mouth,
and throat.
Cellular Entry and Retention
➜ Hematological
Folic acid and many of its analogues are polar,
toxicity is mild to
they cross the blood-brain barrier poorly and
moderate, except for
rare immune-mediated require specific transport mechanisms to enter
cytopenias mammalian cells.
➜ Oxaliplatin may cause 1. A folate receptor, which has high affinity for
leukemia and folic acid but much lower ability to transport
pulmonary fibrosis MTX and other analogues
months to years after 2. The reduced folate transporter, the major
administration. transit protein for MTX, raltitrexed,
➜ Oxaliplatin may cause pemetrexed, and most analogues
an acute allergic 3. A transporter that is active at low pH
response with
urticaria, hypotension, Mechanisms of Resistance to Antifolates
and • Impaired transport of MTX into cells
bronchoconstriction. • Production of altered forms of DHFR that
have decreased affinity for the inhibitor
ANTIMETABOLITES • Increased concentrations of intracellular
FOLIC ACID ANALOGUES DHFR through gene amplification or altered
Is an essential dietary factor that is converted gene regulation
by enzymatic reduction to FH4 cofactors that • Decreased ability to synthesize MTX-PGs
provide methyl groups for the synthesis of • Increased expression of a drug efflux
precursors of DNA (thymidylate and purines) transporter of the MRP class
and RNA. Folic acid analogues such as MTX
interfere with FH4 metabolism (Figure 66–5), ANTIMETABOLITES
reducing the cellular capacity for one-carbon METHOTREX ADME:
transfer and methylation reactions in the ATE Methotrexate is
synthesis of purine ribonucleotides and TMP, readily absorbed
thereby inhibiting DNA replication. from the GI tract at
doses of less than 25
Mechanism of Action mg/m2; larger doses
To function as a cofactor in one-carbon transfer are absorbed
reactions, folate must be reduced by DHFR to incompletely and are
FH4. Inhibitors such as MTX, with a high routinely
administered
affinity for DHFR, cause partial depletion of
intravenously. After
13
intravenous the intestinal
administration, the epithelium. Patients
drug disappears may be at risk for
from plasma in a spontaneous
triphasic fashion. hemorrhage or life-
threatening infection
Therapeutic Uses and may require
Methotrexate is a prophylactic
critical drug in the transfusion of
management of platelets and broad-
childhood ALL. spectrum antibiotics
High-dose MTX is if febrile.
of great value in
remission induction PYRIMIDINE ANALOGUES
and consolidation The pyrimidine antimetabolites encompass a
and in the diverse group of drugs that inhibit RNA and
maintenance of DNA function. The fluoropyrimidines and
remissions in this
certain purine analogues inhibit the synthesis of
highly curable
disease. A 6- to 24-h essential precursors of DNA.
infusion of relatively
large doses of MTX PYRIMIDINE ANALOGUES
may be employed 5- Mechanisms of Action
every 2–4 weeks but FLUOROURA 5-Fluorouracil requires
only when CIL enzymatic conversion
leucovorin rescue (ribosylation and
follows within 24 h phosphorylation) to the
of the MTX nucleotide form to exert its
infusion. cytotoxic activity. As the
Maintenance triphosphate FUTP, the drug
therapy, it is is incorporated into RNA.
administered at a Alternative reactions can
lower dose, orally produce the deoxy derivative
every week. FdUMP; FdUMP inhibits TS
Outcome of and blocks the synthesis of
treatment in children dTTP, a necessary
correlates inversely constituent of DNA
with the rate of drug
clearance. 5-Fluorouracil is
incorporated into both RNA
Adverse Effects and DNA. In 5FU-treated
The primary cells, both FdUTP and dUTP
toxicities of (which accumulates behind
antifolates are on the the blocked TS reaction)
bone marrow and incorporate into DNA in

14
place of the depleted 20% of patients with
physiological TTP. metastatic colon carcinomas,
upper GI tract carcinomas,
ADME: and breast carcinomas but
5-Fluorouracil is rarely is used as a single
administered parenterally agent. 5FU in combination
because absorption after oral with leucovorin and
ingestion of the drug is irinotecan (FOLFOX or
unpredictable and FOLFIRINOX) in adjuvant
incomplete. 5FU is therapy is associated with a
inactivated by reduction of survival advantage for
the pyrimidine ring in a patients with colorectal
reaction carried out by DPD, cancers.
which is found in liver,
intestinal mucosa, tumor FLOXURIDIN The drug is administered
cells, and other tissues. E primarily by continuous
Inherited deficiency of this infusion into the hepatic
enzyme leads to greatly artery for treatment of
increased sensitivity to the patients with metastatic
drug. DPD deficiency can be carcinoma of the colon or
detected by either enzymatic following resection of
or molecular assays using hepatic metastases; the
peripheral white blood cells response rate of intrahepatic
or by determining the plasma infusion (40%–50%) is twice
ratio of 5FU to its of intravenous
metabolite, 5-fluoro-5,6- administration. Intrahepatic
dihydrouracil. arterial infusion for 14–21
days causes minimal
Plasma clearance is rapid (t systemic toxicity; however,
1/2 about 10–20 min). Only there is a significant risk of
5%–10% of a single biliary sclerosis if this route
intravenous dose of 5FU is is used for multiple cycles of
excreted intact in the urine. therapy. Treatment should be
The dose does not have to be discontinued at the earliest
modified in patients with manifestation of toxicity
hepatic dysfunction, (usually stomatitis or
presumably because of diarrhea) because the
sufficient degradation of the maximal effects of bone
drug at extrahepatic sites. marrow suppression and gut
5FU enters the CSF in toxicity will not be evident
minimal amounts. until days 7–14.
CAPECITABI ADME:
Therapeutic Uses: NE The recommended dosage is
5-Fluorouracil. - produces given in two divided doses
partial responses in 10%– with food, for 2 weeks,
15
 followed by a rest period of the treatment of patients with
1 week. Capecitabine is well metastatic colorectal cancers
absorbed orally. who have previously
received other standard
Therapeutic Uses: combination treatments that
an orally administered included FOLFIRINOX.
prodrug of 5FU, is approved Trifluridine and tipiracil are
for the treatment of patients formulated together in a
with single tablet with tipiracil
(1) metastatic breast cancer, added to prevent rapid
who have not responded to a breakdown of trifluridine.
regimen of anthracycline; The trifluridine mechanism
(2) metastatic breast cancer of action mimics that of 5FU
when used in combination
with docetaxel in patients CYTIDINE ANALOGUES
who have had a prior CYTARABINE the most important
anthracycline-containing (CYTOSINE antimetabolite used in the
regimen; and ARABINOSID therapy of AML; it is the
(3)metastatic colorectal E; ARA-C) single most effective
cancer. agent for induction of
  remission in this disease.
Adverse Effects:
The clinical manifestations Mechanisms of Action:
of toxicity caused by 5FU Cytarabine is an
and floxuridine are similar. analogue of 2′-
The earliest untoward deoxycytidine; the 2′-
symptoms during a course of hydroxyl in a position
therapy are anorexia and trans to the 3′-hydroxyl
nausea, followed by of the sugar hinders
stomatitis and diarrhea, rotation of the pyrimidine
reliable warning signs that a base around the
sufficient dose has been nucleoside bond and
administered. Mucosal interferes with base
ulcerations occur throughout pairing. The drug enters
the GI tract and may lead to cells via ENT1 (or
fulminant diarrhea, shock, SLC29A1). It is then
and death, particularly in converted to its active
patients who are DPD form, the 5′-
deficient. monophosphate
TRIFLURIDI Therapeutic Uses: ribonucleotide, by dCK,
NE It is used in eye drops for the an enzyme that shows
treatment of HSV and in a polymorphic expression
fixed combination with amongst. Ara-CMP then
tipiracil, a thymidine reacts with
phosphorylase inhibitor, for deoxynucleotide kinases
16
to form diphosphate and high-dose regimens
triphosphates (Ara-CDP every 12 h for 3–4 days
and Ara-CTP). to achieve 20–50 times
higher serum levels, with
ADME: improved results in
Due to the presence of remission induction and
high concentrations of consolidation for AML.
cytidine deaminase in the
GI mucosa and liver, Adverse Effects:
only about 20% of the The onset of dyspnea,
drug reaches the fever, and pulmonary
circulation after oral Ara- infiltrates on chest
C administration; thus, computed tomographic
the drug must be given scans may follow 1–2
intravenously. Peak weeks after high-dose
concentrations of 2–50 Ara-C and may be fatal
μM are measurable in in 10%–20% of patients,
plasma after intravenous especially in patients
injection of 30–300 being treated for relapsed
mg/m2 but fall rapidly leukemia.
  Intrathecal Ara-C, may
Therapeutic Uses cause arachnoiditis,
The optimal interval seizures, delirium,
between bolus doses of myelopathy, or
Ara-C is about 8–12 h, a coma,especially if given
schedule that maintains concomitantly with
intracellular systemic high-dose MTX
concentrations of Ara- or systemic Ara-C.
CTP at inhibitory levels AZACITIDIN Mechanism of Action
during a multiday cycle E (5- The azanucleosides enter
of treatment. children AZACYTIDIN cells by ENT1
tolerate higher doses than E); (SLC29A1). The drugs
adults. Ara-C is indicated DECITABINE incorporate into DNA,
for induction and where they become
maintenance of remission covalently bound to the
in AML and is useful in DNA methyltransferase,
the treatment of patients depleting intracellular
with other leukemias, enzyme and leading to
Because drug global demethylation of
concentration in plasma DNA that results in
rapidly falls below the tumor cell differentiation
level needed to saturate and apoptosis. Decitabine
transport and also induces double-
intracellular activation, strand DNA breaks,
clinicians have employed perhaps as a consequence
17
of the effort to repair the mild GI symptoms. 5-
protein-DNA adduct. Azacytidine produces
  severe nausea and
ADME vomiting when given
After subcutaneous intravenously in large
administration, 5- doses.
azacytidine undergoes GEMCITABIN Mechanism of Action:
rapid deamination by E Gemcitabine enters cells
cytidine deaminase. Due via three distinct
to the formation of nucleoside transporters:
intracellular nucleotides ENT1, CNT1 and a
that become incorporated nucleobase transporter
into DNA, the effects of found in malignant
the azanucleosides mesothelioma cells.
persist for many hours. Intracellularly, dCK
phosphorylates
Therapeutic Use gemcitabine to the
are approved for monophosphate
treatment of (dFdCMP), which is
myelodysplasia, for converted to di- and
which they induce triphosphates. Although
normalization of bone gemcitabine’s anabolism
marrow in 15%–20% of and effects on DNA in
patients and reduce the general mimic those of
transfusion requirement cytarabine, there are
in one-third of patients distinct differences in
kinetics of inhibition,
The usual treatment additional enzymatic
regimen for 5- sites of action, different
azacytidine in patients effects of incorporation
with MDS is daily for 7 into DNA, and a distinct
days every 28 days, spectrum of clinical
while decitabine is given activity. Unlike of
intravenously every day cytarabine, the
for 5 days every 4 weeks. cytotoxicity of
Best responses may gemcitabine is not
become apparent only confined to the S phase
after two to five courses of the cell cycle.
of treatment.  
ADME:
Adverse Effects Gemcitabine is
The major toxicities of administered as an
the azanucleosides intravenous infusion. The
include pharmacokinetics of the
myelosuppression and parent compound are
18
largely determined by at a fixed rate of 10
deamination in liver, mg/min.
plasma, and other organs,  
and the predominant Adverse Effects:
urinary elimination The principal toxicity is
product is dFdU. In myelosuppression.
patients with significant Longer duration
renal dysfunction, dFdU infusions lead to greater
and its triphosphate myelosuppression and
accumulate to high and hepatic toxicity.
potentially toxic levels. Nonhematological
Gemcitabine has a short toxicities include a flu-
plasma t 1/2 (~15 min); like syndrome, asthenia,
women and elderly and rarely a posterior
patients clear the drug leukoencephalopathy
more slowly. syndrome. Mild,
reversible elevation in
Therapeutic Uses: liver transaminases may
a difluoro analogue of occur in 40% or more of
deoxycytidine (dFdC; see patients. Rarely, patients
Figure treated for many months
66–8), is used for may develop a slowly
patients with metastatic progressive hemolytic
pancreatic; non- uremic syndrome,
squamous, necessitating drug
non–small cell lung; discontinuation.
ovarian; and bladder Gemcitabine is a very
cancer. potent radio-sensitizer
and should not be used
The standard dosing with radiotherapy.
schedule for gemcitabine
is an intravenous infusion PURINE ANALOGUES
on days 1, 8, and 15 of Purine analogues that have valuable roles in
each 21- to 28-day cycle,
leukemia and lymphoid malignancies include
depending on the
cladribine (standard therapy of hairy cell
indication. Conversion of
gemcitabine to dFdCMP leukemia), fludarabine phosphate (standard
by dCK is saturated at treatment of CLL), nelarabine (pediatric ALL),
infusion rates of about 10 and clofarabine (T-cell leukemia/lymphoma).
mg/m2/min. To increase
dFdCTP formation, the 6-Thiopurine Analogues and 6TG
duration of infusion at Approved agents for human leukemia’s and
this maximum function as analogues of the natural purines
concentration has been hypoxanthine and guanine. The substitution of
extended to 100–150 min sulfur for oxygen on C6 of the purine ring
19
creates compounds that are readily transported URINE Absorption of oral
into cells, including activated malignant cells. mercaptopurine is
Nucleotides formed from 6MP and 6TG inhibit incomplete (10%–
de novo purine synthesis and also become 50%); the drug is
incorporated into nucleic acids subject to first-pass
metabolism by
xanthine oxidase in the
Mechanism of Action
liver. Food or oral
Hypoxanthine guanine phosphoribosyl
antibiotics decrease
transferase converts 6TG and 6MP to the absorption. Oral
ribonucleotides 6-thioGMP and 6-thioIMP (T- bioavailability is
IMP), respectively. Because T-IMP is a poor increased when
substrate for guanylyl kinase (the enzyme that mercaptopurine is
converts GMP to GDP), T-IMP accumulates combined with high-
intracellularly. T-IMP inhibits the new dose MTX. After an
formation of ribosyl-5-phosphate, as well as intravenous dose, the t
conversion of IMP to adenine and guanine 1/2 of the drug is about
nucleotides. The most important point of attack 50 min in adults due to
seems to be the reaction of glutamine and rapid metabolic
PRPP to form ribosyl-5-phosphate, the first degradation by
xanthine oxidase and
committed step in the de novo pathway. 6TG
by TPMT.
nucleotide is incorporated into DNA, where it
 
induces strand breaks and base mispairing. Therapeutic Uses:
In the maintenance
Mechanisms of Resistance therapy of ALL, an
➜ The most common mechanism of 6MP initial daily oral dose of
resistance observed in vitro is 6MP is adjusted
Deficiency or complete lack of the according to white
activating enzyme HGPRT or increased blood cell and platelet
alkaline phosphatase activity. Other counts. The
combination of MTX
mechanisms for resistance include:
and 6MP appears to be
➜ decreased drug uptake or increased synergistic. By
efflux due to active transporters; inhibiting the earliest
➜ alteration in allosteric inhibition of steps in purine
ribosyl amine 5-phosphate synthase; synthesis, MTX
and elevates the
➜ impaired recognition of DNA breaks intracellular
concentration of PRPP,
and mismatches due to loss of a
a cofactor required for
component (MSH6) of MMR system
6MP activation.
 
PURINE ANALOGUES Adverse Effects:
MERCAPTOP ADME: The principal toxicity
20
 of 6MP is expression of RNR; or
myelosuppression. increased active
Thrombocytopenia,  
granulocytopenia, or ADME:
anemia may not Cladribine is absorbed
become apparent for orally (55%) but is
several weeks. Dose routinely administered
reduction usually intravenously. It is
results in prompt excreted by the
recovery, although kidneys, with a
myelosuppression may terminal t 1/2 in plasma
be severe and of 6.7 h. Cladribine
prolonged in patients crosses the blood-brain
with a polymorphism barrier and reaches
affecting TPMT. CSF concentrations of
Anorexia, nausea, or about 25% of those
vomiting is seen in seen in plasma. Doses
about 25% of adults, should be adjusted for
but stomatitis and renal dysfunction.
diarrhea are rare;
manifestations of GI Therapeutic Uses:
effects are less frequent Cladribine is
in children than in administered daily for 7
adults. days by continuous
CLADRIBINE Mechanisms of Action intravenous infusion. It
and Resistance: is the drug of choice in
An ADA- Cladribine enters cells hairy cell leukemia.
resistant purine via active nucleoside Eighty percent of
analogue that transport. After patients achieve a
has potent and phosphorylation by complete response after
curative activity dCK and conversion to a single course of
in hairy cell cladribine triphosphate, therapy. The drug also
leukemia, CLL, it is incorporated into is active in CLL; low-
and low-grade DNA. It produces DNA grade lymphomas;
lymphomas. strand breaks and Lang-gerhans cell his-
depletion of NAD and tiyo-sai-tosis; CTCLs,
ATP, leading to including mycosis fun-
apoptosis. It is a potent goy-des and the Sézary
inhibitor of RNR. The syndrome.
drug does not require  
cell division to be Adverse Effects:
cytotoxic. Resistance is The major dose-
associated with loss of limiting toxicity of
the activating enzyme cladribine is
dCK; increased myelosuppression.
21
 Cumulative produces
thrombocytopenia may complete
occur with repeated remissions in
courses. Opportunistic 20%–30% of
infections are common these patients.
and correlate with NELARABINE ADME:
decreased CD4+ cell (6-METHOXY- Infusion, the parent
counts. Other toxic ARABINOSYL methoxy compound is
effects include nausea, -GUANINE) rapidly activated in
infections, high fever, blood and tissues by
headache, fatigue, skin The only ADA–mediated
rashes, and tumor lysis guanine cleavage of the methyl
syndrome. nucleoside in group, yielding the
CLOFARABIN Therapeutic Uses and clinical use. It phosphorylase resistant
E (2- Adverse Effects: has selective Ara-G, which has a
CHLORO-2′- In children, clofarabine activity against plasma t 1/2 of 3 h. The
FLUORO- is administered as a 2-h acute T-cell active metabolite is
ARABINOSYL infusion daily for 5 leukemia and transported into tumor
ADENINE) days. The primary the closely cells, where it is
elimination t 1/2 in related T-cell activated by dCK to
The analogue plasma is 6.5 h. Most lymphoblastic Ara-GTP, which
clofarabine of the drug is excreted lymphoma and incorporates into DNA
incorporates the unchanged in the urine. is approved for and terminates DNA
2-chloro, Doses should be use in patients synthesis. The drug and
glycosylase- adjusted according to with its metabolite Ara-G
resistant reductions in CLCr. relapsed/refracto are primarily
substituent of The primary toxicities ry disease. Its eliminated by
cladribine and a are myelosuppression; basic metabolism to guanine,
2′-fluoro- a clinical syndrome of mechanism of and a smaller fraction
arabinosyl hypotension, action closely is eliminated by renal
substitution, tachyphemia, resembles that excretion of Ara-G.
which adds pulmonary edema, of the other Adults are given a 2-h
stability and organ dysfunction, and purine infusion on days 1, 3,
enhances uptake fever, all suggestive of nucleosides, in and 5 of a 21-day
and capillary leak that it is cycle, and children are
phosphorylation. syndrome and cytokine incorporated given a lower dose for
The resulting release that necessitate into DNA and 5 days, repeated every
compound is immediate terminates DNA 21 days.
approved for the discontinuation of the synthesis.  
treatment of drug; elevated hepatic Adverse Effects:
pediatric ALL enzymes and increased The adverse effects
after failure of bilirubin; nausea, include
two prior vomiting, and diarrhea; myelosuppression and
therapies. and hypokalemia and liver function test
Clofarabine hypophosphatemia. abnormalities, as well
22
 as infrequent serious other week and has a
neurological sequelae, mean terminal t 1/2 of
such as 5.7 h. After hydration
seizures, delirium, with 500–1000 mL of
somnolence, peripheral 5% dextrose in half-
neuropathy, or normal (0.45%) saline,
Guillain-Barré the drug is
Syndrome. administered by rapid
Neurological adverse intravenous injection or
effects may not be by infusion over a
reversible. period of 30 min or
PENTOSTATI Mechanism of Action: less, followed by an
N (2′- Inhibition of ADA by additional 500 mL of
DEOXYCOFO pentostatin leads to fluids.
RMYCIN) accumulation of  
intracellular adenosine Therapeutic Uses:
a transition-state and deoxyadenosine Pentostatin is effective
analogue of the nucleotides, which can in producing complete
intermediate in block DNA synthesis remissions (58%) and
the ADA by inhibiting RNR. partial responses (28%)
reaction, Deoxyadenosine in patients with hairy
potently inhibits (DEOXSE- cell leukemia. It largely
ADA. Its effects ADENOSIN) also has been superseded by
mimic the inactivates S-adenosyl cladribine. Toxic
phenotype of (ADENOSUL) manifestations include
genetic ADA homocysteine myelosuppression, GI
deficiency (HOMOSISTEN) symptoms, skin rashes,
hydrolase. The and abnormal liver
resulting accumulation function studies.
of S-adenosyl
homocysteine is Natural Products
particularly toxic to MICROTUBULE-DAMAGING AGENTS
lymphocytes. VINCA MECHANISM OF
Pentostatin also can ALKALOIDS ACTION
inhibit RNA synthesis, The vinca alkaloids
and its triphosphate Purified alkaloids are cell-cycle–
derivative is from the periwinkle specific agents and, in
incorporated into DNA, plant, including common with other
resulting in strand vinblastine and drugs, such as
breakage. vincristine, were colchicine,
  amongst the earliest podophyllotoxin, the
ADME: clinical agents for the taxanes, and the
Pentostatin is treatment of patients epothilones, block
administered with leukemias, cells in mitosis. The
intravenously every lymphomas, and biological activities
23
testicular cancer. A of the vincas can be vinblastine and
closely related explained by their vinorelbine are all
derivative, ability to bind potent candidates for
vinorelbine, has specifically to β- use in combination
activity against lung tubulin and to block therapy regimens for
and breast cancer. its polymerization leukemias and
with α-tubulin into lymphomas. The lack
microtubules. The of severe
Microtubules are neurotoxicity is a
found in high decided advantage in
concentration in the lymphomas and in
brain and contribute combination with
to other cellular cisplatin against
functions, such as testicular cancer.
movement, ERIBULIN
phagocytosis, and
axonal transport. Synthetic analogue of
halichondrin,
ADME originally isolated
Hepatic CYPs from the Pacific
extensively marine sponge
metabolize all three Halichondria okadai.
drugs, and the The drug binds to the
metabolites are vinca alkaloid site on
excreted in the bile. β-tubulin and inhibits
Only a small fraction micro-tubule
of a dose is found assembly. It is
unchanged in the approved for the
urine. In patients with treatment of patients
hepatic dysfunction with drug-resistant
(bilirubin > 3 mg/dL), metastatic breast
a 50%–75% reduction cancer and
in dose of any of the liposarcoma.
vinca alkaloids is
advisable. ESTRAMUSTINE ADME:
Following oral
ADVERSE Combines estradiol administration, at
EFFECT and normustine least 75% of a dose of
Adverse effects of the through a carbamate estramustine
vinca alkaloids, such link. Although the phosphate is absorbed
as their neurotoxicity, intent of the from the GI tract and
may relate to combination was to rapidly
disruption of these enhance the uptake of dephosphorylated.
functions. the alkylating agent The drug undergoes
Vincristine, into estradiol- extensive first-pass
24
sensitive prostate metabolism by impaired glucose
cancer cells, hepatic CYPs to an tolerance; and
estramustine does not active 17-keto hypersensitivity
function in vivo as an derivative, reactions, including
alkylating agent; estromustine, and to angioedema.
rather, it binds to β- multiple inactive Estramustine inhibits
tubulin and products; the active the clearance of
microtubule- drug forms taxanes.
associated proteins, accumulate in the EPOTHILONES
causing microtubule prostate. Some
disassembly and hydrolysis of the The epothilones are
antimitotic actions. carbamate linkage polyketides
occurs in the liver, discovered as
releasing estradiol, cytotoxic metabolites
estrone, and the from a strain of
normustine group. Sorangium
Estramustine and cellulosum, a
estromustine have myxobacterium
plasma half-lives of isolated from soil on
10 and 14 h, the bank of the
respectively, and are Zambezi River in
excreted as inactive southern Africa.
metabolites, mainly
in the feces.
CAMPTOTHECIN ANALOGUES
Therapeutic Use: The camptothecins are potent, cytotoxic
Estramustine is used antineoplastic agents that target the nuclear
solely for the enzyme topoisomerase I. The lead compound
treatment of patients in this class, camptothecin, was isolated from
with metastatic or
the tree Camptotheca acuminata.
locally advanced
hormone-refractory
prostate cancer. Mechanism of Action
The DNA topoisomerases are nuclear enzymes
Adverse Effects: that reduce torsional stress in supercoiled
Myelosuppression DNA, allowing selected regions of DNA to
and estramustine are become sufficiently untangled to permit
possesses estrogenic replication, repair, and transcription. Two
side effects classes of topoisomerase (I and II) mediate
(gynecomastia, DNA strand breakage and resealing.
impotence, elevated Camptothecin analogues inhibit the function of
risk of thrombosis, topoisomerase
and fluid retention);
hypercalcemia; acute
attacks of porphyria; CAMPTOTHECIN ANALOGUES
TOPOTECAN ADME:
25
Topotecan is approved small cell lung cancer
for intravenous is a 30-min infusion
administration. An for 5 consecutive days
oral dosage form in every 3 weeks.
development has a
bioavailability of Adverse Effects:
30%–40% in patients The dose-limiting
with cancer. toxicity with all
Topotecan exhibits dosing schedules is
linear neutropenia, with or
pharmacokinetics, and without
it is rapidly eliminated thrombocytopenia. In
from systemic patients with
circulation with a half hematological
life of about 3.5–4.1 malignancies, GI side
hours. Doses should effects such as
be reduced in mucositis and diarrhea
proportion to become dose limiting.
reductions in CLCr. Other less common
Hepatic metabolism and generally mild
appears to be a topotecan-related
relatively minor route toxicities include
of drug elimination. nausea and vomiting,
The Plasma protein elevated liver
binding of topotecan transaminases, fever,
is low (7%–35%), fatigue, and rash,
which may explain its Irinotecan
relatively greater CNS IRINOTECAN ADME:
penetration. The conversion of
irinotecan to its active
THERAPEUTIC metabolite SN-38 is
USES: mediated
Topotecan is indicated predominantly by
for previously treated carboxylesterases in
patients with ovarian the liver. Although
and small cell lung SN-38 can be
cancer. Significant measured in plasma
hematological toxicity shortly after beginning
limits its use in an intravenous
combination with infusion of irinotecan,
other active agents in the AUC of SN-38 is
these diseases. The only about 4% of the
recommended dosing AUC of irinotecan,
regimen of topotecan suggesting that only a
for ovarian cancer and relatively small
26
fraction of the dose is this incidence by more
ultimately converted than half. However,
to the active form of once severe diarrhea
the drug. Irinotecan occurs, standard doses
exhibits linear of antidiarrheal agents
pharmacokinetics. In tend to be ineffective.
comparison to The second most
topotecan, a relatively common irinotecan-
large fraction of both associated toxicity is
irinotecan and SN-38 myelosuppression.
are present in plasma Severe neutropenia
as the biologically occurs in 14%–47% of
active intact lactone the patients treated
form. with a schedule of
administration every 3
Therapeutic Uses: weeks and is less
Single-agent dosage frequently
of irinotecan is by encountered amongst
weekly infusion for 4 patients treated with
of 6 weeks, with a the weekly schedule. 
higher dose given ANTIBIOTICS
every 3 weeks. In DACTINOMYCIN MECHANISM OF
patients with (ACTINOMYCIN ACTION:
advanced colorectal D) The capacity of
cancer, irinotecan is actinomycins to bind
used as first-line Actinomycins are to double-helical
therapy in chromopeptides DNA is responsible
combination with isolated from for their biological
fluoropyrimidines or Streptomyces soil activity and
as a single agent or in bacteria. Most cytotoxicity. The
combination with contain the same planar phenoxazone
cetuximab following chromophore, the ring intercalates
failure of a planar phenoxazone between adjacent
5FU/oxaliplatin actinosin, which is guanine-cytosine base
regimen.  responsible for their pairs of DNA, while
yellow-red color. the polypeptide chains
Adverse Effects: The differences extend along the
The dose-limiting amongst naturally minor groove of the
toxicity with all occurring helix, resulting in a
dosing schedules is actinomycins are dactinomycin-DNA
delayed diarrhea, with confined to complex with stability
or without variations in the sufficient to block the
neutropenia. An structure of the transcription of DNA
intensive regimen of amino acids of the by RNA polymerase.
loperamide  reduces peptide side chains.
27
Actinomycin D has ADME: suppression with
beneficial effects in Dactinomycin is pancytopenia may
the treatment of solid administered by occur in the first week
tumors in children intravenous injection. after completion of
and choriocarcinoma Metabolism of the therapy. Proctitis,
in adult women. drug is minimal. The diarrhea, glossitis,
drug is excreted in cheilitis, and
both bile and urine ulcerations of the oral
and disappears from mucosa are common;
plasma with a terminal dermatological
half life of 36 hrs. manifestations include
Dactinomycin does alopecia, as well as
not cross the blood- erythema,
brain barrier. desquamation, and
increased
Therapeutic Uses: inflammation and
Dactinomycin is given pigmentation in areas
intravenously for 5 previously or
days, usually in the concomitantly
range of 10–15 μg/kg. subjected to X-ray
If no manifestations of radiation.
toxicity are ANTHRACYCLIN ADME:
encountered, ES AND Daunorubicin,
additional courses ANTHRACENEDI doxorubicin,
may be given at ONES epirubicin, and
intervals of 2–4 idarubicin are
weeks, although Anthracyclines are administered
weekly maintenance derived from the intravenously and are
doses have been used. fungus Streptomyces cleared by a complex
The main clinical use peucetius var. pattern of hepatic
of dactinomycin is in caesius. Idarubicin metabolism and
the treatment of and epirubicin are biliary excretion. Each
rhabdomyosarcoma analogues of the anthracycline is
and Wilms tumor in naturally produced converted to an active
children. anthracyclines alcohol intermediate
doxorubicin and that plays a variable
ADVERSE daunorubicin, role in the therapeutic
EFFECT: differing only activity. The plasma
Toxic manifestations slightly in chemical disappearance curves
include anorexia, structure, but having for doxorubicin and
nausea, and vomiting, somewhat distinct daunorubicin an
usually beginning a patterns of clinical multiphasic, with a
few hours after activity. terminal t 1/2 of 30 h.
administration. Daunorubicin and Idarubicin has a t 1/2
Hematopoietic idarubicin primarily of 15 h, and its active
28
 metabolite, is a biphasic pattern of
idarubicinol, has a t clearance with a terminal t
1/2 of 40 h. The drugs 1/2 of about 6–8 h in
rapidly enter the heart, patients with normal renal
kidneys, lungs, liver, function. Approximately
have been used in
and spleen; they do 40% of an administered
acute leukemias,
not cross the dose is excreted intact in
whereas doxorubicin
bloodbrain barrier. the urine.
and epirubicin
Clearance is delayed
display broader THERAPEUTIC USES:
in the presence of
activity against solid The intravenous dose of
hepatic dysfunction; at
tumors.  etoposide for testicular
least a 50% initial
reduction in dose cancer in combination
should be considered therapy (with bleomycin
in patients with and cisplatin) is 50–100
elevated serum mg/m2 for 5 days or 100
bilirubin levels. mg/m2 on alternate days
for three doses. For small
EPIPODOPHYLLOTOXINS cell carcinoma of the lung,
Podophyllotoxin Derivatives the dosage in combination
Two synthetic derivatives of podophyllotoxins therapy (with cisplatin) is
100–200 mg/m2 /d
have significant therapeutic activity in pediatric
intravenously for 3 days.
leukemia, small cell carcinomas of the lung,
The Cycles of therapy
testicular tumors, Hodgkin disease, and large usually are repeated every
cell lymphomas.  3–4 weeks. After relapse,
oral administration of 50
MECHANISMS OF ACTION AND mg/m2/d for 21 days is one
RESISTANCE treatment option. 
Etoposide and teniposide form ternary
complexes with topoisomerase ii and dna and ADVERSE EFFECTS:
prevent resealing of the break that normally The dose-limiting toxicity
follows topoisomerase binding to dna. the of etoposide is leukopenia
enzyme remains bound to the free end of the (nadir at 10–14 days,
recovery by 3 weeks).
broken dna strand, leading to an accumulation
Thrombocytopenia occurs
of dna breaks and cell death. 
less often and usually is
not severe. Nausea,
EPIPODOPHYLLOTOXINS vomiting, stomatitis, and
ETOPOSIDE ADME: diarrhea complicate
Oral administration of treatment in about 15% of
etoposide results in patients. Alopecia is
variable absorption that common but reversible. 
averages about 50%. After TENIPOSIDE
intravenous injection, there

29
Teniposide is
administered DRUGS OF DIVERSE MECHANISMS OF
intravenously. It ACTION
has a BLEOMYCIN ADME:
multiphasic Bleomycin is
pattern of The bleomycins, a administered
clearance from unusual group of intravenously,
plasma: After DNA-cleaving intramuscularly, or
distribution, a t antibiotics, are subcutaneously or
1/2 of 4 h and fermentation instilled into the bladder
another t1/2 of products of for local treatment of
10–40 h are Streptomyces bladder cancer. Having a
observed. verticillus, high molecular mass,
Approximately comprising a bleomycin crosses the
45% of the drug family of peptide blood-brain barrier
is excreted in polyketides. The poorly. The elimination t
the urine; in drug currently 1/2 is about 3 h. About
contrast to employed two-thirds of the drug is
etoposide, as clinically is a excreted intact in the
much as 80% is mixture of two urine. Concentrations in
recovered as copper-chelating plasma are greatly
metabolites. peptides, elevated in patients with
Anticonvulsants bleomycins A2 renal impairment, and
such as and B2 that differ doses of bleomycin
phenytoin only in their should be reduced in the
increase the terminal amino presence of a CLCr less
hepatic acid. Because their than 60 mL/min.
metabolism of toxicities do not
teniposide and overlap with those Therapeutic Uses:
reduce systemic of other cytotoxic Bleomycin is given
exposure. drugs and because weekly or twice weekly
Teniposide is of their unique by the intravenous,
available for mechanism of intramuscular, or
treatment of action, bleomycin subcutaneous route. A
refractory ALL maintains an test dose of 2 units or
in children and important role in less is recommended for
is synergistic treating Hodgkin patients with lymphoma.
with cytarabine. disease and Bleomycin also may be
Teniposide is testicular cancer. instilled into the pleural
administered by cavity in doses of 5–60
intravenous mg to ablate the pleural
infusion for 5 space in patients with
days or twice malignant effusions. 
weekly. MITOTANE ADME :
Approximately 40% of
30
 mitotane is absorbed ADVERSE EFFECTS:
after oral administration. Although the
Plasma concentrations of administration of
mitotane are still mitotane produces
measurable for 6–9 anorexia and nausea in
weeks following most patients,
discontinuation of somnolence and lethargy
therapy. A water-soluble in about 34%, and
metabolite of mitotane dermatitis in 15%–20%.
found in the urine These effects do not
constitutes 25% of an contraindicate the use of
oral or parenteral dose. the drug at lower doses.
About 60% of an oral Because this drug
Mitotane is a
dose is excreted damages the adrenal
compound
unchanged in the stool. cortex, administration of
chemically similar
replacement doses of
to the insecticides
THERAPEUTIC adrenocorticosteroids is
DDT and DDD, is
USES: necessary.
used in the
Mitotane initial daily TRABECTEDIN ADME:
treatment of
oral doses are 2–6 g, Trabectedin is
adrenal cortex
usually in three or four Trabectedin is administered as a 24-h
carcinoma. The
divided portions. The derived from the infusion of 1.3 mg/m2
mechanism of
maximal tolerated dose marine every 3 weeks. It is
action of mitotane
may vary from 2 to 16 invertebrate administered with
has not been
g/d. Treatment should tunicate dexamethasone, 4 mg
elucidated, but its
continue for at least 3 Ecteinascidin twice daily, starting 24 h
relatively selective
months; if beneficial turbinate. before drug infusion to
destruction of
effects are observed, Trabectedin is an diminish hepatic
adrenocortical
therapy should be alkylating drug toxicity. The drug is
cells, normal or
maintained indefinitely. that binds to the slowly cleared by
neoplastic, is well
Spironolactone should minor groove of CYP3A4, with a plasma
established.
not be administered DNA, allowing t 1/2 of about 24–40 h.
concomitantly because it the alkylation of
interferes with the the N2 position of Therapeutic Uses:
adrenal suppression guanine and Trabectedin is approved
produced by mitotane. bending the helix for the treatment of
Treatment with mitotane toward the major patients with
is indicated for the groove. unresectable or
palliation of inoperable metastatic liposarcoma
adrenocortical or leiomyosarcoma after
carcinoma, producing an anthracycline-
symptomatic benefit in containing regimen and
30%–50% of such is under study as an
patients. orphan drug for the
treatment of patients
31
 with ovarian and treatment are
pancreatic cancer. retinoids, in
particular tretinoin
Adverse Effects: (ATRA), which
Without dexamethasone induces a high rate
pretreatment, trabectedin of complete
causes significant remission in
hepatic enzyme patients with APL
elevations and fatigue in as a single agent
at least one-third of and, in
patients. With the combination with
steroid, the increases in anthracyclines,
transaminase are less cures most
pronounced and rapidly patients with this
reversible. Other disease. 
toxicities include mild ARSENIC Mechanism of Action
myelosuppression TRIOXIDE The basis for ATO’s
and,rarely, antitumor activity
rhabdomyolysis. Arsenic trioxide remains uncertain. APL
RETINOIDS (As2O3), known cells have high levels of
as ATO, is a ROS and are quite
One of the highly effective sensitive to further ROS
hallmarks of treatment of induction. ATO inhibits
malignant relapsed APL, thioredoxin reductase
transformation is a producing and thereby generates
block in complete ROS. 
differentiation. A responses in more
number of than 85% of such ADME
chemical entities patients Arsenic trioxide is well
such as vitamin D absorbed orally but in
and its analogues, cancer treatment is
retinoids, administered as a 2-h
benzamides and daily intravenous
other inhibitors of infusion in dosages of
HDAC, various 0.15 mg/kg/d for up to
cytotoxic and 60 days, until remission
biological agents, is documented. The drug
and inhibitors of enters cells via one of
DNA methylation several glucose
can induce transporters. The
differentiation in primary mechanism of
tumor cell lines. elimination is through
The most enzymatic methylation.
important of these Multiple methylated
for cancer metabolites form rapidly
32
 and are excreted in 6. Immune function, amongst other
urine. Less than 20% of advances.
administered drug is Drivers of Cancer Growth
excreted unchanged in I. Growth Factors and Receptors in
the urine. No dose Cancer Cells
reductions are indicated II. Intracellular Kinases in Cancer Cells
for hepatic or renal
III. Tumor Angiogenesis
dysfunction.
IV. Targeting the Immune System
Adverse Effects V. Other Drugs and Targets that control
Pharmacological doses Cancer Cell Behavior
of ATO are well
tolerated. Patients may 2 Classes of Pathway-Targeted Cancer
experience reversible Drugs
side effects, including Monoclonal Antibodies:
hyperglycemia, hepatic Monoclonal antibodies kill tumor cells by
enzyme elevations, blocking cell surface receptor function, by
fatigue, dysesthesias, recruiting immune cells and complement to the
and light-headedness. antigen-antibody complex, and by modulating
Fewer than 10% of
immune cell function.
patients experience a
leukocyte maturation
syndrome similar to that Small Molecules:
seen with ATRA, Small molecules may attack the same
including pulmonary targets as monoclonal antibodies but can exert
distress, effusions, and their effect by entering cells. Often inhibit
mental status changes. multiple enzymes with different selectivities

Pathway-Targeted Therapies PATHWAY-TARGETED THERAPIES

A Note on Treatment Regimens
Cancer treatment regimens change to reflect GROWTH FACTORS AND RECEPTORS
continuous advances in basic and clinical IN CANCER CELLS
science: 1. Inhibitors of EGFR Function
1. New drugs, both small molecules and 2. HER2/NEU Inhibitors
biological 3. Inhibitors of PDGF Receptor
2. Improved methods of targeting and 4. Hedgedog Pathway Inhibitors
timing of drug Delivery
3. Agents with altered pharmacokinetic INHIBITORS OF EGFR FUNCTION
properties and Selectivities The EGFR belongs to the ErbB family of
4. the use of rational multidrug transmembrane receptor tyrosine kinases also
combinations known as ErbB1 or HER1 (human EGFR 1).
5. Greater knowledge of the basic cell EGFR is essential for the growth and
biology of tumorigenesis, metastasis, differentiation of epithelial cells.
and
33
 Ligand binding to the extracellular domain of Gefitinib inhibits by binding
EGFR family members causes receptor to the intracellular enzyme
dimerization and stimulates the protein tyrosine (tyrosine kinase) of the EGFR
kinase activity of the intracellular domain. to directly block signals
turned on by triggers outside
Two separate classes of drugs that target the or inside the cell.
EGFR pathway:
ADME
1. PROTEIN TYR KINASE Oral bioavailability is about
INHIBITORS 60%; PPC are achieved
(erlotinib, gefitinib, afatinib, osimertinib) within 3–7 h. Absorption of
2. MONOCLONAL ANTIBODIES gefitinib is not significantly
(cetuximab, panitumumab, necitumumab) altered by food. Metabolism
of gefitinib is predominantly
PROTEIN TYR KINASE INHIBITORS via CYP3A4,
Mechanism of Action
Erlotinib is a reversible Therapeutic Uses
inhibitor of the EGFR Treatment of patients with
tyrosine kinase, competitively metastatic NSCLC with
inhibiting ATP binding at the EGFR mutations or lung
active site of the kinase. cancer.

ADME Adverse Effects and Drug

60% absorbed after oral Interactions.
administration. PPL occur Diarrhea and skin reactions
after 4h and metabolized by occur in more than 20% of
CYP3A4 patients.
AFATINIB Mechanism of Action
Therapeutic Uses Erlotinib Afatinib is a second-
ERLOTINIB is used to treat certain types generation, orally
of NSCLC It is also approved bioavailable, irreversible
for the treatment of patients inhibitor of EGFR (HER1)
with pancreatic cancer. and HER2 receptor kinases

Adverse Effects and Drug ADME

Interactions The elimination is 37h after
Rash, diarrhea, anorexia, repeat dosing in patients with
fatigue, dyspnea, nail cancer. In patients with
disorders, nausea, and severe renal impairment, a
vomiting. Serious adverse dose reduction is
reactions include severe rash recommended.
Fatal interstitial lung disease
occurs with a frequently and Therapeutic Uses
fatal hepatic failure. First-line treatment of
GEFITINIB Mechanism of Action patients with metastatic

34
 NSCLC with EGFR and left ventricular
mutations and patients with dysfunction.
metastatic squamous NSCLC.
Antibody Inhibitors of EGFRs
Adverse Effects and Drug
Interactions 1. Cetuximab
Diarrhea and skin 2. Panitumumab
rash/acneiform dermatitis,
3. necitumumab
stomatitis, as well as hand-
foot skin reactions. Also
observed are interstitial lung HER2/Neu Inhibitors
disease, liver function Is a recombinant, fully humanized IgG2κ
abnormalities, and left antibody that binds to the extracellular domain
ventricular dysfunction. III of the EGFR and prevents ligand- dependent
Resistance to Gefitinib, Erlotinib, and signaling. It is FDA approved for the treatment
Afatinib of EGFR and as monotherapy after disease
Mechanism of Action progression
Osimertinib is a third- HER2/Neu Inhibitors
generation, orally TRASTUZUMA
bioavailable, irreversible B
inhibitor of T790M-mutant PERTUZUMAB
EGFR, Lapatinib is an orally
bioavailable, small-
ADME LAPATINIB
molecule inhibitor of the
Osimertinib is a substrate EGFR and HER2
Of CYP3A. The drug is tyrosine kinases.
primarily eliminated in the Neratinib is an orally
feces and to a lesser extent in bioavailable, irreversible
the urine. Concurrent NERATINIB inhibitor of the HER2
administration of inducers of and EGFR protein
OSIMERTINI
CYP3A4 may necessitate an tyrosine kinase
B
increase in the dose.

Therapeutic Uses. INHIBITORS OF PDGF RECEPTOR

Osimertinib is approved for Signaling by the PDGFR plays a significant
metastatic NSCLC that has part in mesenchymal biology, including stem
progressed after treatment cell growth, and is involved in oncogenesis
and is positive for the EGFR through aberrant cancer cell signaling,
T790M mutation. modulation of the tumor microenvironment,
and facilitation of angiogenesis and metastasis.
Adverse Effects and Drug PDGF INHIBITORS
Interactions OLARATUM Mechanism of Action
Diarrhea and skin rash. Also AD Olaratumab is a human
observed are interstitial lung IgG1 monoclonal antibody
disease, QTc prolongation, that binds to PDGFRα and
35
 blocks ligand-mediated Dabrafenib is an frequency, are
receptor activation. orally hyperkeratosis,
bioavailable, headache, pyrexia,
is a first-in-class hedgehog small-molecule arthralgia, papilloma,
VISMODEGI signaling pathway inhibitor inhibitor of alopecia, and PPES. An
B approved for the treatment mutated forms of increased incidence of
of adult patients with BCC. BRAF kinases. cuSCC is expected with
a hedgehog pathway Dabrafenib can a median time of 2
inhibitor that binds to and inhibit the months to the first
SONIDEGIB inhibits SMO receptor proliferation of diagnosis.
signal transduction similar tumor cells. Is
to vismodegib used to treat a
certain types of
INTRACELLULAR PROTEIN KINASES melanoma
IN CANCER CELLS COBIMETINIB Adverse Effect
The RAS-RAF-MEK-ERK Pathway Diarrhea,
HRAS and KRAS, named after Harvey and Cobimetinib is an photosensitivity
orally reaction, nausea,
Kirsten rat sarcoma viruses and discovered in
bioavailable, pyrexia, and vomiting.
the early 1980s, were the first oncogenes
reversible Major hemorrhagic
discovered in human tumors. The first RAF inhibitor of events can occur with
gene was identified from a murine retrovirus MEK1/2 protein cobimetinib; patients
named “rapidly accelerated fibrosarcoma” kinase activity. Its should be monitored for
Due to its oncogenic effects. Following the elimination half- signs and symptoms of
discovery of the first human RAF gene, ARAF life ranges from 1 bleeding. The drug also
and BRAF were identified; their gene products to 3 days. It is increases the risk of
are ser/thre protein kinases. used to treat a cardiomyopathy.
RAS-RAF-MEK-ERK INHIBITORS certain type of
VEMURAFENIB Adverse Effects metastatic
Arthralgia, fatigue, and melanoma
Vemurafenib is an nausea are also observed INHIBITORS OF MEK KINASE
orally bioavailable but at a lower frequency. TRAMETINIB Adverse Effects
inhibitor of The median time to the Cutaneous rash,
mutated BRAF. first appearance of these Trametinib was acneiform dermatitis,
This drug is used skin lesions. Increased the first inhibitor and diarrhea. Fatigue,
to treat a type of photosensitivity of the MEK nausea, and lymphedema
skin cancer reactions can be family to be FDA also occur. Serious grade
(melanoma). prevented with sunblock. approved. It is 3–4 skin toxicity is
Vemurafenib used to treat found in 6% of patients.
works by slowing certain types of
the growth of cancer in people Drug Resistance
certain cancer who have a Activation of alternative
cells. "BRAF" gene signaling pathways
DABRAFENIB Adverse Effects mutation. signaling can bypass
In order of decreasing MEK inhibition and
36
Trametinib is an result in drug-resistant breast cancer as thrombocytopenia.
orally tumors. well as a variety
bioavailable, of other cancers.
reversible. BRUTON TYROSINE KINASE
Bioavailability of INHIBITOR
oral trametinib is Mechanism of Action
72% and is Ibrutinib is an orally
reduced if taken bioavailable, small-
with a high-calorie molecule inhibitor that
meal. inactivates BTK Use to
INHIBITORS OF JAK1 AND JAK2 treat Mantle Cell
RUXOLTINIB Adverse Effect Carcinoma.
The most common
Ruxolitinib is adverse reactions, ADME
indicated for the thrombocytopenia and Administration with
treatment of anemia, should be met food roughly doubles
IBRUTINIB
patients with with a dose reduction or absorption. The
polycythemia vera discontinuation of elimination half-life of
who have had an treatment. ibrutinib is 4 to 6 h
inadequate
response to Adverse Effect
hydroxyurea and Neutropenia, pyrexia,
for the treatment thrombocytopenia,
of myelofibrosis. hemorrhage, anemia,
CYCLIN-DEPENDENT KINASE diarrhea, nausea,
PALBOCICLIB Adverse Effect musculoskeletal pain,
The most common rash, and fatigue
Palbociclib is the adverse effects of
first CDK palbociclib are BCR-ABL Kinase Inhibitors
inhibitor approved neutropenia, leukopenia, Imatinib mesylate, originally named “sti 571”
by the FDA for infections, stomatitis, was the first protein kinase inhibitor designed
the treatment of fatigue, nausea, anemia, to target a driver mutation in a cancer and to
advanced or headache, diarrhea, and receive FDA approval.
metastatic breast thrombocytopenia. It was approved in 2001 under the name
cancer that is ER
Gleevec and is now designated as an essential
positive and
HER2 negative drug by the World Health Organization.
ABEMACICLIB Adverse Effect INHIBITORS OF THE BCR-ABL
& RIBOCICLIB The most common KINASE
adverse effects of IMATINIB
These inhibitors palbociclib are DASATINIB
are currently neutropenia, leukopenia, NILOTINIB
undergoing infections, stomatitis, INHIBITORS OF THE BCR-ABL
clinical trials in fatigue, nausea, anemia, KINASE
patients with headache, diarrhea, and BOSUTINIB Bosutinib is another

37
 second-generation. It is P13K inhibitors cause cell death, inhibit
FDA approved for the proliferation of malignant cells and interfere
treatment of patients with several signaling pathways.
with chronic, The inhibition of mTOR blocks the binding of
accelerated, or blast- the accessory protein raptor, which reduces
phase Ph+CML with protein synthesis and decrease cell mortality
resistance or intolerance
and size
to prior therapy
INHIBITOR OF P13K
Ponatinib is a third-
Therapeutic uses:
generation BCR-ABL
Approved for the
kinase inhibitor.
treatment of relapsed or
Imatinib lacks efficacy
refractory B-cell
for the more advanced
PONATINIB malignancies in
disease phases, and cells
patients who have
with mutations in the
IDELALISIB received at least two
BCR-ABL tyrosine
prior systemic therapies
kinase domain are
Adverse effect:
resistant
Liver toxicity, diarrhea,
colitis, pneumonitis,
Inhibitors of Anaplastic Lymphoma Kinase
intestinal perforations,
ALK is a substance that blocks the activity of a skin toxicity
protein, which helps control cell growth. INHIBITOR OF mTOR
Blocking the protein help keep cancer cells Therapeutic uses:
from growing and spreading. Temsirolimus and
Inhibitors of Anaplastic Lymphoma everolimus are
Kinase approved for treatmet
Therapeutic uses: of patients with
Approved for the advanced renal cancer.
treatment of Temsirolimus prolongs
patients with survival and delays
advanced or disease progression in
RAPAMYCIN
recurrent NSCLC patients with advanced
ANALOGUE
ALECTINIB and poor- or
CERITINIB Adverse effect: intermediate-risk renal
CRIZOTINIB GI toxicity and cancer
hepatotoxicity. Adverse effect:
Bradycardia, Hyperglycemia,
prolonged QT hypertriglyceridemia
intervals, fatigue, and rarely pulmonary
constipation and infiltrates and
edema interstitial lung disease
MULTIKINASE INHIBITORS
Inhibitors of the P13K/Akt/mTOR Pathway CABOZANTINI Therapeutic uses:
B Cabozantinib was also

38
 shown to produce congestive, heart failure,
superior efficacy to impaired wound healing,
sunitinib in patients spontaneous GI perforation
with treatment-naïve
intermediate- or poor- The most common adverse
risk metastatic renal effects are hypertension
cancer and diarrhea
Adverse effect: ANTIANGIOGENIC SMALL-
Diarrhea, fatigue, MOLECULE KINASE INHIBITOR
nausea, decreased Therapeutic Uses:
appetite, PPES, Approved for the treatment
hypertension, vomiting, of pancreatic NETs and of
weight loss, GISt in patients who have
constipation developed resistance to
imatinib
Tumor Angiogenesis Sofafenib is the only drug
Cancer cells secrete angiogenic factors that currently approved for
induce the formation of new blood vessels and treatment of patients with
guarantee the flow of nutrients to the tumor hepatocellular-carcinoma
cells to permit growth and metastasis and for the patients with
metastatic renal cell cancer
Angiogenesis plays a critical role in the growth
SUNITINIB
of cancer because solid tumors need a blood SORAFENID Adverse Effect:
supply. Bleeding, hypertension,
INHIBITION VEGF and VEGFR proteinuria and
PATHWAY uncommonly arterial
BEVACIZUM Therapeutic Uses: thromboembolic events
AB Use to treat ovarian cancer and intestinal perforation
RAMUCIRUM combined with Fatigue, nausea, diarrhea,
AB chemotherapy and renal anorexia, rash and palmar-
AFLIBERCEP cell carcinoma combined plantar erthrodysesthesias;
T with interferon uncommonly, bone
marrow suppression, GI
Metastatic colorectal perforation and
cancer in combination of cardiomyopathy occur
chemotherapy OTHER RECEPTOR KINASE
INHIBITOR WITH ANTIANGIOGENIC
It is indicated for patients EFFECTS
with mCRC that is Axitinib is approved for
resistant to or has the treatment of patients
progressed following an AXITINIB with advanced RCC after
oxaliplatin containing failure of one prior
regimen systemic therapy
LENVATINIB Lenvatinib is approved for
Adverse effect:
the treatment of patients
Hypertension, related
39
 with recurrent or metastatic Mechanism of Action
differentiated thyroid Ipilimumab blocks the
cancer and in combination interaction of CTLA-4
with everolimus for with B7 ligands on
patients with advanced APCs and thereby
renal cell cancer. augments T-cell
activation.
TARGETING THE IMMUNE SYSTEM ADME
AND OTHER TARGETS Ipilimumab is
IMMUNE CHECKPOINT INHIBITORS administered
The conceptual breakthrough is based on the intravenously.
discovery of inhibitory signals that limit T-cell
Therapeutic Uses
activation, so called immune activation. The Current recommended
discovery of receptors, ligands, and their IPILIMUMAB dosing of iplimumab is
function in the control of immune cell activity 3 mg/kg intravenously
during the past two decades led to the a fully human
over 90 min every 3
development of clinically effective monoclonal lgG1 monoclonal
weeks for a total of four
antibody that
antibodies that enable T cells to recognize and doses for patients with
binds to CTLA-4
eradicate cancer cells with acceptable adverse metastatic disease and
and is approved
effects. 10 mg/kg followed by
for the treatment
Mechanism of T-Cell Activation 10 mg/kg every 12
of late stage
Antigen-mediated activation of T cells is weeks for up to 3 years
melanoma and
initiated by engagement of the TCR with or until documented
under study for
disease recurrence or
antigen presented on MHC protein on the other cancers.
unacceptable toxicity for
surface of an APC, “signal 1.”
patients treated in the
This “signal 2” is provided by B7 surface adjuvant setting.
proteins on APCs, for example, CD80 or Adverse Effect
CD86. T-cell activation is tightly controlled by Blockade of CTLA-4
immune-suppressive cells and cytokines as compromises immune
well as by coinhibitory molecules present on T tolerance to some
cells, such as CTLA-4 or PD-1. normal tissue antigens
and provokes
INHIBITORS OF CYTOTOXIC T inflammatory toxicities,
LYMPHOCYTE–ASSOCIATED PROTEIN mostly in the skin,
4 (CTLA4) pituitary gland,
The CTLA-4 is upregulated during the antigen intestine, and liver.
Other Drugs in This
priming of T cells and binds B7 on APCs to
Class
attenuate the T-cell response and thus reduce
TREMELIMU
the risk for chronic autoimmune-dependent MAB
inflammation.
CYTOTOXIC LYMPHOCYTE- (formerly
ASSOCIATED PROTEIN 4 (CTLA4) ticilimumab) is a
40
 fully human common than with CTLA-4
IgG2 monoclonal antibodies; corticosteroids
antibody that are recommended based on
targets CTLA-4; the severity of the reaction.
it is under ADME; Clinical Use
investigation in The recommended treatment
several clinical schedule for pembrolizumab
trials. is 2 mg/kg (or a 200-mg flat
dose) as an intravenous
infusion over 30 min every
Inhibitors of Programmed Cell Death 1 (PD- Pembrolizuma 3 weeks. The elimination
b half-life is 26 days.
1)
Activation of the PD-1 checkpoint pathway in Pembrolizumab
T cells by PD-L1 or PD-L2 evokes a negative Adverse Effect
(formerly called
regulatory immune response and inactivates T The most common adverse
lambrolizumab
cells. effects, experienced by
or MK-3475) is
more than 20% of patients,
PROGRAMMED CELL DEATH 1 (PD-1) a humanized
are fatigue, cough, nausea,
INHIBITOR monoclonal
pruritus, rash, decreased
Nivolumab Mechanism of Action IgG4-κ isotype
appetite, constipation,
Nivolumab is a fully human antibody that
arthralgia, and diarrhea. An
monoclonal IgG4 antibody blocks
additional 10% of patients
that blocks the interaction interaction
may experience
between PD-1 and its between PD-1
complications with
ligands. and its ligands.
infections. Serious adverse
events include immune-
ADME; Clinical Use
mediated inflammation,
Nivolumab is administered
specifically pneumonitis,
as an intravenous infusion
colitis, hepatitis, and
every 2 weeks until the time
hypophysitis and both
of disease progression or of
hyper- and hypothyroidism.
unacceptable toxicity.

Adverse Effects Antagonist of PD-1 Ligand 1

In patient with Melanoma, Programmed cell death 1 has two ligands, PD-
Rash (>20%) L1 and PD-L2, each with distinct expression
profile. The PD-L1 ligand is expressed on
In patient with advance APCs, T cells, B cells, and nonhematopoietic
squamous NSCLC cells, which can include cancer cells.
Fatigue, dyspnea,
musculoskeletal pain, ATEZOLIMU Mechanism of Action
decreased appetite, cough, MAB Atezolizumab, also known
nausea, and constipation. as MPDL3280A, is a fully
human IgG1 monoclonal
Immune-mediated adverse
antibody that blocks the
reactions are much less
41
interaction of PD-L1 with Therapeutic Uses:
PD-1 and B7-H1. DURVALUMA Evaluated for efficacy
B AND toward cancers of the head
ADME AVELUMAB and neck, stomach, lung
Atezolimumab is and ovary, as well as
administered as an hepatocellular cancer
intravenous infusion over
60 min every 3 weeks. The COMBINATION OF ANTI- PD-1 AND
terminal half-life is 27 ANTI-CTLA4
days. Anti-CTLA-4 and anti-PD-1 target distinct
immune checkpoints during T-cell activation,
Clinical Use
Atezolimumab is indicated preclinical studies have shown that concurrent
for conventional treatment- targeting of CTLA-4 and PD-1 significantly
resistant metastatic NSCLC improves therapeutic efficacy when compared
as well as locally advanced to effects of single agents.
or metastatic urothelial
cancer. CYTOKINES TO STIMULATE
IMMUNE RESPONSE
Adverse Effect: INTERLEUKIN 2 Mechanism of
Patient with metastatic Action:
NSCLC; fatigue, decreased 70 or so proteins It stimulates the
appetite, dyspnea, cough, and glycoproteins proliferation of
nausea,musculoskeletal that are classified activated T cells and
pain, constipation as cytokines, only secretion of cytokines
IFN and IL-2 are from NK cells and
Patient with urothelial routine clinical use, monocytes. IL-2
carcinoma may have often for actions stimulations increases
urinary infection against cancer cytotoxic killing by T
cells and NK cells
Immune-related adverse
effect; hepatitis, colitis, ADME:
hypophysitis, thyroid Administered
disorders, adrenal intravenously. The
insufficiency, type 1 serum t1/2 of IL-2
diabetes mellitus, after intravenous
pancreatitis, myasthenia administration has an α
gravis, Guillain-barre phase of about 13 min
syndrome, ocular and a β phase of about
inflammation, these may 90 mins. Il-2 is
require discontinuation of excreted in the urine as
treatment. an inactive metabolite.
Female should be advised Therapeutic uses:
accordingly due to potential Aldesleukin possesses
embryo-fetal toxicity.
42
 the biological activities laherparepvec) is an
of native human IL-2. oncolytic herpesvirus that
The drug us approved replicates within tumors
for use in patients with and expresses GM-CSF.
metastatic renal cancer Tumor antigens are
and metastatic released after virally
melanoma. induced cell death, and
the presense of GM-CSF
Adverse effect: can promote an antitumor
Dominated by the immune response
capillary leak
syndrome, in which Chimeric Antigen Receptor T Cells
intravascular fluid CARS contain the antigen-binding domain of a
leaks into the monoclonal antibody to confer recognition of
extravascular space, the targeted tumor antigen coupled to
producing
intracellular domains capable of activating T
hypotension, edema,
respiratory difficulties, cells.
confusion, tachycardia,
oliguric renal failure,
electrolyte problems.
Symptoms include
fever, chills, malaise,
nausea, vomiting,
diarrhea

CANCER VACCINES
Future challenges of immunotherapy
Vaccination against cancer antigens has shown
The potential for immunotherapies to augment
little efficacy with the exception of two
conventional chemotherapy pathway- targeted
approaches that were approved by the FDA in
treatment, and radiotherapy will require
2010 (sipuleucel-T) and in 2015 (T-VEC)
detailed exploration and will be a common
theme in the design of future clinical trials
CANCER VACCINES
A cell-based approach
INHIBITORS OF POLY (ADP-RIBOSE)
designed to induce an
immune response against POLYMERASE
PAP, which is expressed DNA damage-repair genes are frequently
in most prostate cancers. inactivated in human cancer. PARP1 is the
SIPULEUCEL- product of one such gene. PARP1 is a nuclear
This autologous cellular
T protein that transfers ADP-ribose from NAD to
immunotherapy is
generated from a patients target proteins, and this poly (ADP-ribosyl)
peripheral blood cells, ation (or PARylation) of nuclear proteins by
which are isolated by PARP1 plays a significant role in the DNA
leukapheresis damage response. Inactive PARP1 associates
T-VEC T-VEC (talimogene
43
with chromatin and helps to create a compact with
chromatin structure in the nucleosome. Germline BRCA-
The mechanisms of relaxation are the mutated, advanced,
PARylation of PARP1 itself, and of histones ovarian cancer who
and other chromatin associated proteins. have been treated with
Resulting in their dissociation from DNA. three or more prior lines
of chemotherapy.
The synthesis and degradation of PAR chains
in vivo is tightly regulated, with the chains Adverse effects:
having half-lives measured in minutes (Wei GI upset (nausea and
and Yu, 2016). vomiting) and loss of
Deficient PARP1 activity leads to defective appetite; fatigue; muscle
DNA repair. However, PARP-deficient cells and joint pain; low
are still able to carry out DNA repair through a blood cell counts and
different mechanism homologous anemia; and
recombination. The protein machinery for occasionally leukemia.
homologous recombination repair includes the Potentially fatal MDS
breast cancer susceptibility genes BRCA1 and and pneumonitis have
BRCA2, suggesting that cells with diminished been observed.
Clinical use:
or absent BRCA1/2 function could be
The drug is
unusually susceptible to the inhibition of PARP
administered orally but
activity. should not be given until
Olaparib and rucaparib are approved for the RUCAPARIB
the patient has
treatment of patients with advanced ovarian recovered from any
cancer. Is a
benzimidazole hematological toxicity
INHIBITORS OF POLY (ADP-RIBOSE) caused by previous
derivative that
POLYMERASE chemotherapy. WP2D6
inhibits PARP1.
OLAPARIB ADME: Rucaparib is FDA metabolizes Rucaparib,
Rapidly absorbed after approved for yielding a half-like of
An orally oral administration and about 18 h.
treatment of
bioavailable metabolized primarily advanced ovarian
inhibitor of PARP by CYP3A4, yielding a Adverse effect:
cancer in patients
enzyme t1/2 of about 12 h. Drug GI upset and abdominal
exhibiting
exposure is increased or pain, fatigue, and
deleterious
reduced when decreased appetite.
BRCA mutations
administered in MDS and AML rare but
who have been
combination with serious adverse effects
treated with at
CYP3A4 inhibitor or (<1%). This
least two prior
inducer, respectively agent may cause fetal
chemotherapies.
harm and should not be
Therapeutic uses: administered to pregnant
Olaparib is EMA and females or used by
FDA approved as nursing mothers.
monotherapy in patients BCL2 INHIBITORS
44
The BCL2 protein family comprises moFe fatigue. Venetoclax
than 20 proteins that goveFn mitochondrial should not be
outeF membrane peFmeabilization administered during
and control pFogFammed cell death pregnancy or
apoptosis). breastfeeding until
VENETOCLAX Mechanism of Action: further data are
A first-in-class, orally available.
bioavailable, small-
molecule inhibitor of Thalidomide and Lenalidomide
BCL2. It was designed Thalidomide originally was used for the
as a BH3 mimetic that treatment of pregnancy-associated morning
inhibits BCL2 sickness but was withdrawn from the market
interaction with the due to teratogenicity and dysmelia (stunted
proapoptotic BH3-only
limb growth).
family members, such as
BIM, BID, and BAD.
Further research revealed its antiangiogenic
ADME: and immunomodulatory effects. At least four
Oral absorption is distinct mechanisms have been proposed to
significantly improved explain its antitumor activity.
3- to 5-hold by
administration with a Both thalidomide and lenalidomide possess
meal. Venetoclax, a Pgp potent
substrate, is metabolized Activity in patients with newly diagnosed and
by CYP3A4/5; heavily pre-treated relapsed/refractory MM.
concomitant use of Lenalidomide also is approved for its activity
CYP3A inhibitors or
in the 5q — subset [or del (5q) subset] of
inducers and Pgp
inhibitors should be MDS. A specific gene array profile identifies
avoided. The patients with MDS who lack the 5q —
elimination half-life is abnormality but respond to Ienalidomide. A
18—26 h. more recently added derivative of thalidomide
is porn Lenalidomide, approved for treatment
Therapeutic use: of patients with MM resistant to Lenalidomide.
Approved for the LENALIDOMIDE ADME:
treatment of patients
with CLL with a 17p Lenalidomide The standard dosage
deletion. constitutes the lead of lenalidomide is 25
compound of mg/d for 21 days or a
Adverse effect: immunomodulatory 28-day cycle.
Neutropenia, diarrhea, thalidomide The drug is rapidly
nausea, anemia, upper derivatives. absorbed following
respiratory tract Lenalidomide oraI administration,
infection, induces the teaching peak plasma
thrombocytopenia, ubiquitination and levels within 1.5 h.
45
degradation of involvement, and carpal tunnel syndrome
target proteins by Therapeutic Uses: POMALIDOMID
the E3 ubiquitin Lenalidomide exhibits E Adverse effects are
ligase CRL4CRBN. potent antitumor similar to those of
Target proteins in activity in MM, MDS, A thalidomide thalidomide.
MM cells are and CLL; this agent congener, is
IKZF1/3, which are causes fewer adverse indicated for the
crucial for cell effects and lacks the treatment of
survival. In MDS, teratogenicity of patients with MM
casein kinase 1A1 is thalidomide. who have received
the target protein at least two prior
Adverse effect: therapies including
Are less severe; it lenalidomide.
causes little sedation, PROTEASOME INHIBITORS (FIRST
constipation, or GENERATION)
neuropathy. BORTEZOMIB Mechanism of
Lenalidomide Action:
depresses bone First generation Bortezomib binds to
marrow function and inhibitor of the β5 subunit of the
is associated with proteasome- 205 core of the 26S
significant leukopenia mediated protein proteasome and
(20% of patients). degradation that has reversibly inhibits its
Hepatotoxicityand a central role in the chymotrypsin-like
renal dysfunction are treatment of MM activity. This event
rare. In some patients disrupts multiple
with CLL, intracellular signalling
lenalidomide causes cascades, leading to
dramatic lymph node apoptosis. An
swelling and tumor important
lysis (tumor flare consequence of
reaction). proteasome inhibition
Adverse effect of Thalidomide and is its effect on NP-
lenalidomide: KB, a transcription
Thalidomide is well tolerated at doses less factor that promotes
than 200 mg daily. Common adverse effects cell damage response
are sedation and constipation. The most and cell survival.
serious adverse effect is peripheral sensor Most cellular NF-kB
neuropathy, which occurs in 10%—30% of is cytosolic and bound
patients with MM or other malignancies in a to ITB; in this form,
dose- and time-dependent manner. NP-<B is restricted to
Thalidomide-related neuropathy is an the cytosol and cannot
asymmetrical, painful, peripheral paresthesia enter the nucleus to
with sensor loss, commonly presenting with regulate transcription.
numbness of toes and feet, muscle cramps, In response to stress
weakness, signs of pyramidal tract signals resulting from
46
hypoxia, chronic of the
chemotherapy, and toxicities, develops
DNA damage, ITB most frequently in
becomes ubiquitinated patients with a prior
and then degraded via history of neuropathy
the proteasome secondary to prior
drug treatment (e.g.,
ADME: thalidomide) or
The recommended diabetes or with
starting dose of prolonged use.
bortezomib is 1.3
mg/m 2 given as an SECOND GENERATION
intravenous bolus on A second-generation
days 1, 4, B, and 11 of selective proteasome
every 21 -day cycle CARFILZOMIB inhibitor based on
{with a 10-day rest tetrapeptide
period per cycle). At epoxyketone
Ieast 72 h should an orally bioavailable
elapse between doses. second-generation
peptide analogue
Therapeutic Uses: proteasome inhibitor
Bortezomib is used as IXAZOMIB
that interacts with
initial therapy for subunit beta type 5
patients with MM and (PSMB5) of the 20S
as therapy for patients proteasome complex
with MM after relapse This agents
from other drugs. It is mechanisms of action
also approved for include inhibition of
treatment of patients protein translation by
with relapsed or preventing the initial
refractory MCL. OMACETAXINE
elongation step of
protein synthesis,
Adverse effect: thereby depleting the
Bortezomib toxicities cell of short-lived
include proteins
thrombocytopenia
(28%), fatigue (12%), CD20 INHIBITORS
peripheral neuropathy
A cell surface antigen expressed on the surface
(12%), neutropenia,
anemia, vomiting, of all B cells beginning with the pro—B cell
diarrhea, limb pain, stage through its terminal differentiation to
dehydration, nausea, plasma cells and is expressed on about 90% of
and weakness. B-cell neoplasms.
Peripheral
neuropathy, the most CD20 INHIBITORS

47
RITUXIMAB ADME: infusion rates and
The drug is antihistamines.
Chimeric administered by Uncommonly, patients
murine/human intravenous infusion may develop severe
monoclonal IgG1 both as a single agent mucocutaneous skin
antibody that and in combination with reactions including
targets the CD20 chemotherapy. Drug 5tevens-Johnson
B-cell surface half-life is about 22 syndrome. Rituximab
antigen days. may cause reactivation
of hepatitis B virus or
Therapeutic Uses: rarely, JC virus (with
Rituximab is approved progressive multifocal
as a single agent for leukoencephalopathy)
relapsed indolent a second monoclonal
lymphomas and antibody that binds to
significantly enhances CD20 at sites on the
response and survival in OFATUMUMA major and minor
combination with B extracellular loops of
chemotherapy for the CD20, distinct from the
initial treatment of site targeted by
diffuse large BCL. rituximab
Rituximab improves A humanized
response Fates when monoclonal IgG1
added to combination OBINUTUZUM antibody that recognizes
chemotherapy for other AB the CD20 antigen
indolent B-cell NHLs, expressed on the surface
including ALL, MCL, of B-cells
WM, and marginal zone OTHER CELL SURFACE TARGETS
lymphomas. FOR MONOCLONAL ANTIBODIES
ALEMTUZUM Therapeutic Uses:
Resistance and AB Approved as a single
Adverse effect: agent for the treatment
Resistance to rituximab A humanized of B-cell CLL. Clinical
may emerge through IgG-K activity had been
down regulation of monoclonal demonstrated in both B-
CD20, impaired antibody that and T-cell lowgrade
antibody- dependent binds to CD52 lymphomas and CLL,
cellular cytotoxicity antigen. CD52 is including patients with
decreased complement found on the disease refractory to
activation limited effects surface of a purine analogues.
on signalling and subset of normal
induction of apoptosis neutrophils and Adverse effects:
and inadequate blood on all B and T Serious toxicities
levels. lymphocytes, on include acute infusion
All respond to decreased testicular reactions and depletion
48
 of normal neutrophils that recognizes sites on
and T cells. the surfaces of B cells
Myelosuppression with and T cells, thereby
depletion of all blood enabling a patients T
lineages, occurs in the cells to recognize
majority of MAB malignant B cells.
Patients and may Bilitumomab binds
elements and
represent either direct simultaneously to CD3
sperm, and on
marrow toxicity or (part of the TCR) on T
most BCLs and
autoimmune responses. cells and to CD19 on B
T-cell
Immunosuppression cells.
lymphomas.
leads to a significant MONOCLONAL ANTIBODY-
risk of fungal, viral, and CYTOTOXIN CONJUGATES
other opportunistic Mechanism of Action:
infections, particularly A humanized
in patients who have monoclonal antibody
previously received against CD33 covalently
purine analogues. linked to a
a monoclonal antibody semisynthetic derivative
that targets glycolipid of calicheamicin, a
GD2, expressed on potent antitumor
DINUTUXIMA neuroblastoma cells and antibiotic.
B on normal cells of
neuroectodermal origin, ADME:
including the CNS and The antibody conjugate
GEMTUZUMA
peripheral nerves produces a 30%
B
A human IgG1 complete response rate
OZOGAMICIN
monoclonal antibody in relapsed AML when
that binds to CD38 and administered at a dose 9
inhibits the growth of mg/m2 for up to three
DARATUMUM doses at 2-week
CD38- expressing tumor
AB intervals
cells by inducing
immune-mediated tumor
cell lysis through CDC Therapeutic Uses:
and ADCC The drug was initially
A humanized approved for use in
monoclonal IgG1 patients more than 60
antibody that targets years of age with AML
SLAMF7 (CD319). It is in first relapse.
ELOTUZUMAB approved for the BRENTUXIMA An anti-Cd30 IgG1
treatment of patients B VEDOTIN monoclonal antibody
with MM who have linked with the
received one to three microtubule-disrupting
prior therapies agent MMAE. CD30 is
BILINATUMO A bispecific antibody expressed on a number
49
 of malignant cells and is in combination with
especially prevalent in G-CSF to mobilize
Hodgkin and anaplastic HSC to the
lymphoma peripheral blood for
Ado-trastuzumab-DM1 collection and
combines the HER2- subsequent
targeted properties of autologous
trastuzumab with the transplantation in
ADO- antimicrotubule agent patients with NHL
TRASTUZUMA DM1 (derived from and MM.
B EMTANSINE maytansine), allowing
preferential intracellular INHIBITORS OF HISTONE
rug delivery to HER2+ DEACETYLASE
cells in the treatment of Histone deacetylases are a class of enzymes
HER+ breast cancer that catalyse the removal of acetyl groups from
ADME: acetylated lysine amino acids in histones,
Administered by
thereby altering the transcriptional activation of
intravenous infusion
cellular genes
DENILEUKIN over 30-60 min for 5
DIFTITOX consecutive days every ADME:
21 days for 8 cycles. The oral bioavailability
An immunotoxin The drug is quickly is about 21%.
made from the distributed and has Panobinostat is
genetic terminal t ½ of about 70 PANOBINOSTA metabolised through
recombination of min. T CYP3A. it is
IL-2 and the recommended to avoid
catalytically Therapeutic Uses: An orally concomitant use with
active fragment of Approved for the bioavailable, strong CYP3A4
diphtheria toxin treatment of nonselective pan- inducers or inhibitors.
recurrent/refractory HDAC inhibitor. Otherwise, dose
cutaneous T-cell The inhibitory adjustments will be
lymphomas. activity leads to necessary. The
CYTOKINES AND GROWTH FACTORS apoptosis of elimination half-life is
malignant cells approximately 37 h
Colony-Stimulating Factors
via multiple
Many agents used for cancer chemotherapy
pathways Adverse effect:
suppress the production of multiple types of Diarrhea,fatigue,nausea,
hematopoietic cells, and bone marrow peripheral edema,
suppression can limit the delivery of decreased appetite,
chemotherapy on schedule and at prescribed pyrexia, vomiting
doses ROMIDEPSIN ADME:
PLERIXAFOR a small-molecule After intravenous
inhibitor of the An HDAC administration, the
CXCr4 chemokine inhibitor used in major metabolism is
receptor and is used the treatment of through CYP3A4
cutaneous and
50
 Adverse effects: thrombocytopenia,
Nausea and vomiting, anorexia, and dysgeusia.
anemia, Patients with severe
peripheral T-cell
thrombocytopenia, hepatic impairment
lymphoma
leukopenia as well as should be excluded from
abnormal electrolyte treatment. Vorinostat is
levels and ECG changes classified as pregnancy
VORINOSTAT Mechanism of Action category D: evidence of
Vorinostat binds to the risk.
A small- active site of HDACs
molecule, orally and chelates zinc ions in Hormones and Related Agents in the
bioavailable the active site. The Therapy of Cancer
HDAC inhibitor; resulting inhibition of DRUGS THAT TARGET THE
it is also known HDACs causes the GLUCOCORTICOID RECEPTOR
as SAHA based accumulation of Glucocorticoids act by binding to a specific
on its chemical acetylated histones and
GR that is a member of the nuclear receptor
name other acetylated
suberanilohydrox family of transcription factors. The GR
proteins, amongst which
amic acid are transcription factors translocates to the nucleus and induces
crucial for cell complex gene expression changes that lead to
differentiation. anti-proliferative and apoptotic responses in
sensitive cells. In acute lymphoblastic or
ADME undifferentiated leukemia of childhood,
The absorption of glucocorticoids may produce prompt clinical
vorinostat is slightly improvement and objective hematological
improved when taken remissions in 30% of children.
with a meal. Metabolism
is mostly through ESTROGENS AND ANDROGENS IN
glucuronidation and
CANCER
hydrolysis. The
elimination t1/2 is about
2 h. ■ Hormone Therapy of Breast Cancer
High doses of estrogen have been recognized
Therapeutic Use; as effective treatment of breast cancer. More
Adverse Effects recent studies have suggested lower doses of
Vorinostat is approved estrogen can be effective in the management of
for the treatment of endocrine-resistant disease.
patient with cutaneous However, interruption of estrogen-induced
T-cell lymphoma with signaling with anti-estrogens such as tamoxifen
persistent or recurrent and drugs that reduce estrogen production have
disease after two
been found to be more effective and better
systemic therapies. The
tolerated. These drugs have largely replaced
most comma n adverse
reactions are diarrhea, estrogens or androgens for the treatment of
fatigue, nausea, breast cancer.

51
 (hot flashes), atrophy
■ Hormone Therapy of Prostate Cancer of the lining of the
Drugs That Target the Estrogen Receptor vagina, menstrual
TAMOXIFEN Mechanism of irregularities, vaginal
Action: bleeding and
The most widely Tamoxifen is a discharge, and
studied anti- competitive inhibitor pruritus vulvae and
estrogenic drug used of Estrogens binding occur with increasing
in the treatment of to the ER, and severity in
breast cancer. These antagonizes postmenopausal
novel anti-estrogens estrogen-induced women years.
can be divided into proliferation of Tamoxifen slightly
tamoxifen analogues; human breast cancer. increases the risk of
fixed ring compunds; Binding of estrogen thromboembolic
and the SERDs, the and SERMs to the events, which
latter also termed estrogen-binding increase with the age
“pure antiestrogen” sites of the ERs of a patient and also
initiates a change in in the perioperative
was developed as an conformation of the period. Hence, it
oral contraceptive ER, dissociation of often is advisable to
the ER from heat- temporarily halt
Tamoxifen is shock proteins, and tamoxifen prior to
prescribed for the ER dimerization. elective surgery.
adjuvant therapy of Therapeutic Uses:
early-stage breast TOREMIFENE Toremifene is used
Therapeutic Uses:
cancer and for the Tamoxifen is used occasionally in the
therapy of advanced for the treatment of a triphenylethylene
metastatic setting for
breast. derivative of
women with ER+ the treatment of
tamoxifen and has a
metastatic breast breast cancer in
Tamoxifen is also similar
cancer or following women with tumors
used for the pharmacological
primary excision of that are ER+ or of
prevention of breast profile, clinical
an ER+ tumor as an unknown receptor
cancer in high-risk efficacy, and safety
adjuvant treatment to status.
patients such as those prevent recurrence pharmacological
with a strong family and extend overall profile, clinical Adverse Effect:
history or prior efficacy, and safety In rare case it can
survival. For the
nonmalignant breast adjuvant treatment of cause heart rhythm
pathology. premenopausal problems through
.
women, prolongation of the
QT interval
Adverse effect:
The common adverse SELECTIVE ESTROGEN RECEPTOR
reactions to DOWNREGULATORS (SERDs)
tamoxifen include
vasomotor symptoms
52
The SERDS, also termed pure antiestrogens, setting as the third-
include fulvestrant and a number of agents in generation AI
experimental trials. SERDs, unlike SERMs, are anastrozole.
devoid of any estrogen agonist activity.
FULVESTRANT Mechanism of
Action: Adverse Effect:
is currently the  Fulvestrant is a Most common adverse
only FDA- steroidal effects includes
approved SERD, antiestrogen nausea, asthenia, pain,
either as a single that binds to hot flashes, arthralgias,
agent or in the ER with an and headache. The risk
combination with affinity more of injection site
palbociclib, a than 100 times reactions, seen in
CDK4/6 inhibitor that of almost 10% patients, is
for postmenopausal tamoxifen. reduced by giving the
women with HR+  The drug not injection slowly.
metastatic breast only inhibits
cancer that has the binding of
progressed on anti- AROMATASE INHIBITORS
estrogen but
estrogen therapy.  Aromatase converts androgens to estrogens.
also alters the
receptor  AIs Aromatase (CYP19A1) is responsible
structure such for the conversion of adrenal androgens and
that the gonadal androstenedione and testosterone
receptor is to the estrogens estrone (E1) and estradiol
targeted for (E2), In postmenopausal women, this
proteasomal conversion occurs in non-ovarian tissues
degradation and is the primary source of circulating
 fulvestrant also estrogens. Therapy or after tamoxifen block
may inhibit this enzymatic activity, thereby reducing
receptor estrogen production .
dimerization.
 AIs are now considered the standard of care
Therapeutic Uses: for adjuvant treatment of postmenopausal
Fulvestrant is used in women with ER+ breast cancer, either as
postmenopausal initial.
women as antiestrogen
therapy of HR+ First- and second-generation
metastatic breast  AIs are no longer used for breast cancer
cancer after treatment because of their side effects.
progression on first-  Third-generation inhibitors include the type
line antiestrogen 1 steroidal agent exemestane and the type 2
therapy such as
nonsteroid imidazoles anastrozole and
tamoxifen or an AI.
letrozole
Fulvestrant is at least
as effective in this
53
 they are approved for use in post- EXEMESTANE
menopausal women
 Third-generation AIs are Used as part of a more potent, orally
the treatment of early-stage and advanced administered
analogue of the
breast cancer in postmenopausal women Therapeutic Uses:
natural aromatase
and for chemoprevention. The use of the mTOR
substrate
inhibitor everolimus
androstenedione and
Therapeutic Uses: with exemestane has
ANASTROZOLE lowers estrogen
AIs are approved for been approved for
levels more
up-front adjuvant treatment of
Is absorbed rapidly effectively than does
hormonal therapy for advanced-stage breast
after oral its predecessor,
5–10 years or cancer that has
administration formestane.
following prior progressed on
Steady state is Exemestane
tamoxifen in nonsteroidal type 2
attained after 7 days irreversibly
postmenopausal Ais GnRH Agonists
of repeated dosing. inactivates aromatase
women with early- and is a “suicide
Anastrozole is
stage breast cancer substrate” type 1
metabolized by N-
and as treatment of inhibitor of
dealkylation,
advanced and aromatase.
hydroxylation, and
metastatic breast
glucuronidation.
cancer. In early-stage Drugs That Target the Progesterone
breast cancer, anastro- Receptor
The main metabolite
zole is significantly
of anastrozole is a  Progestational agents are mainly used as
more effective than
triazole. Less than secondary agents in hormonal therapy for
tamoxifen in delaying
10% of the drug is metastatic hormone-dependent breast
time totumor
excreted as the cancer and are also used in the management
recurrence and
unmetabolized parent
decreasing the odds of of endometrial carcinoma previously
compound.
a primary treated by surgery and radiotherapy.
contralateral tumor.  Medroxyprogesterone acetate is available
Therapeutic Uses: for oral administration; an alternative oral
The clinical progestational agent is megestrol acetate.
LETROZOLE indications for use of Beneficial effects have been observed in
letrozole in breast one-third of patients with endometrial
The clinical uses and cancer treatment are
cancer. The response of breast cancer to
side-effect profile of the same as for
the type 2 AI megestrol is predicted by both the presence
anastrozole In
letrozole are similar addition, improved of HRs (ER and PR) and the evidence of
to that detailed in the progression-free response to a prior hormonal treatment
previous section for survival is observed
anastrozole. when HR+ advanced Hormone Therapy of Prostate Cancer
stage breast cancer is  Androgens stimulate the growth of normal
treated. and cancerous prostate cells. These findings
established androgen deprivation therapy
54
 (ADT) as the mainstay of treatment for decrease LH production; therefore, testosterone
patients with advanced prostate cancer. levels are normal or increased. Men treated
 ADT is also given in conjunction with with antiandrogen maintain some degree of
radiation therapy or following surgery for potency and libido and do not have the same
some men with regionally localized spectrum of side effects seen with castration.
intermediate- to high-risk disease. However, antiandrogen therapy is typically
 In patients with metastasis, ADT is given in combination with ADT.
typically the standard first-line treatment. Antiandrogens are classified as steroidal,
including cyproterone or nonsteroidal,
Androgen Deprivation Therapy including enzalutamide, flutamide,
GnRH Agonists and Antagonists bicalutamide, and nilutamide.
The most common form of ADT involves
chemical suppression of the pituitary gland is the most recently
with GnRH agonists (see previous section). FDA-approved second-
GnRH agonists in common use for prostate generation antiandrogen.
cancer include leuprolide, goserelin, triptorelin, It prolongs survival in
histrelin, and nafarelin Long-acting patients with metastatic
CRPC when given to
preparations are available in doses that are
chemotherapy naïve
approved for 3-, 4-, and 6-month patients or after
administrations. ENZALUTAMI
docetaxel therapy.
Toxicity DE
During the transient rise in LH, the resultant Enzalutamide is a
testosterone surge may induce acute synthetic nonsteroidal
stimulation of prostate cancer growth and a antiandrogen that has 5-
“flare” of symptoms from metastatic deposits. to 8-fold higher binding
Patients may experience an increase in bone affinity for the AR
pain, spinal cord compression, or obstructive compared to
bladder symptoms lasting for 2–3 weeks. bicalutamide.
The flare phenomenon can be effectively BICALUTAMID The agent bicalutamide
E is given once daily in
counteracted with concurrent administration of
conjunction with a
2–4 weeks of oral anti-androgen therapy, which GnRH agonist.
may inhibit the action of the increased serum Bicalutamide has a 1/2
testosterone levels. of 5–6 days.
Bicalutamide undergoes
Drugs That Target the Androgen Receptor glucuronidation to
Antiandrogens bind to Ars and competitively inactive metabolites,
inhibit the binding of testosterone and and the parentcompound
dihydrotestosterone, thereby preventing AR and metabolites are
nuclear translocation and inhibiting eliminated in bile and
transcription of downstream androgen- urine. The 1/2 of
responsive genes. Unlike castration, bicalutamide is
increased in severe
antiandrogen therapy by itself does not
55
 hepatic insufficiency that also inhibits both
and is unchanged in testicular and adrenal
renal insufficiency. steroidogenesis by
given orally once daily. blocking CYP 11A and
It has an elimination 1/2 primarily
of 45 h and is Ketoconazole is
metabolized to five administered off label
products that are all as secondary hormone
LE
excreted in the urine. therapy to reduce
Common side effects adrenal androgen
NILUTAMIDE include mild nausea, synthesis in CRPC.
alcohol intolerance Diarrhea and hepatic
(5%–20%), and enzyme elevations
diminished ocular limit its use as initial
adaptation to darkness hormone therapy.
(25%–40%); rarely,
interstitial pneumonitis ABIRATERONE Mechanism of Action
occurs. Abiraterone inhibition
is given orally three used with of CYP17A1 reduces
times per day. It has a t prednisone for the the conversion of
1/2 of 5 h; its major treatment of CRPC pregnenelone and
metabolite, in patients who are progesterone to their
hydroxyflutamide, is chemotherapy 17α-hydroxy
biologically active. naïve or in those derivatives and
FLUTAMIDE Common side effects who have received reduces the synthesis
include diarrhea, breast previous docetaxel. of DHEA and
tenderness, and nipple In both settings, it androstenedione. Thus,
tenderness. Less prolongs survival. circulating levels of
commonly, nausea, testosterone drop to
vomiting, and almost-undetectable
hepatotoxicity occur. levels after abiraterone
administration.
Drugs That Inhibit Androgen Synthesis
 In the castrate state, AR signaling, despite
low steroid levels, supports continued Estrogens
prostate cancer growth. AR signaling may High estrogen levels can reduce testosterone to
occur due to androgens produced from non- castrate levels in 1–2 weeks via negative
gonadal sources, AR gene mutations, or AR feedback on the hypothalamic-pituitary axis.
gene amplification. Estrogen also may compete with androgens for
steroid HRs and may thereby exert a cytotoxic
 Androstenedione, produced by the adrenal
effect on prostate cancer cells. Although
glands, is converted to testosterone in
estrogens reduce bone loss and are as effective
peripheral tissues and tumors.
as orchiectomy for metastatic prostate cancer,
KETOCONAZO is an antifungal agent
56
They are no longer used clinically because of  Prepare the lining of the uterus
their risk for serious and potentially fatal side for a fertilized egg
effects as well as impotence and lethargy.  Support pregnancy
 Suppress estrogen production
DRUGS AFFECTING THE FEMALE after ovulation
REPRODUCTIVE SYSTEM
Phase Range
FEMALE SEX HORMONES
Hormones are natural substances produced in before puberty 0.1–0.3 ng/mL
the body. They help to relay messages between
cells and organs and affect many bodily during first
functions. Everyone has what are considered (follicular) stage of 0.1–0.7 ng/mL
“male” and “female” sex hormones. menstrual cycle

TYPES OF FEMALE SEX HORMONES while ovulating

2–25 ng/mL
ESTROGEN (luteal stage of cycle)
Estrogen is the major female hormone. These
first trimester of
share comes from the ovaries, but small 10–44 ng/mL
pregnancy
amounts are produced in the adrenal glands and
fat cells. During pregnancy, the placenta also second trimester 19.5–82.5 ng/mL
makes estrogen.
third trimester 65–290 ng/mL
The roles of estrogen:
 Puberty
TESTOSTERONE
 Menstruation Testosterone is a hormone that is responsible
 Pregnancy for many of the physical characteristics specific
 Menopause to adult males. It plays a key role in
Normal ranges in picograms per milliliter reproduction and the maintenance of bone and
(pg/mL): muscle strength.
 Adult female, The role of testosterone:
 premenopausal: 15-350 pg/mL  Sexual desire
 Adult female, postmenopausal: <10  Regulation of the menstrual cycle
pg/mL  Bone and muscle strength
 Adult male: 10-40 pg/mL  The normal range for females is 15 to 70
nanograms per deciliter (ng/dL).
PROGESTERONE
The ovaries produce the female sex hormone CHANGES IN THE ROLES THAT THE
progesterone after ovulation. During HORMONES PLAY OVER TIME
pregnancy, the placenta also produces some. ● Puberty
The role of progesterone: ● Menstruation
● Sexual desire and contraception
57
 ● Pregnancy ★ Progesterone thickens the cervix to protect
● After childbirth and breastfeeding the uterus from bacteria and sperm.
● Perimenopause and menopause Estrogen levels are also higher,
contributing to the thickening of the lining
PUBERTY of the uterus.
★ Between ages of 8 and 13. ★ As soon as conception takes place, you start
★ The luteinizing hormone (LH) and follicle- to produce human chorionic gonadotropin
stimulating hormone (FSH) are produced in hormone (hCG).
the pituitary gland. ★ Human placental lactogen (hPL) is a
★ Production increases at puberty, which in hormone made by the placenta.
turn stimulates the sex hormones — ★ Levels of another hormone called relaxin
especially estrogen. also rise during pregnancy.
This increase in female sex hormones results
in: AFTER CHILDBIRTH AND
1. Development of the breast BREASTFEEDING
2. Growth of pubic and armpit hair ★ Once pregnancy ends, hormone levels
3. An overall growth spurt start to fall immediately.
4. Increase in body fat, especially in the ★ Breastfeeding lowers estrogen levels
hips and thighs
and can prevent ovulation.
5. Maturation of the ovaries, uterus, and
vagina
PERIMENOPAUSE & MENOPAUSE
6. Start of menstrual cycle
★ During perimenopause — the period
MENSTRUATION
leading up to menopause — hormone
★ The first menstrual period (menarche)
production in the ovaries slows down.
happens about two to three years after the
Estrogen levels begin to fluctuate while
breasts begin to develop.
progesterone levels start a steady
★ Most females get their first period between decline.
the ages of 10 and 16.
SEXUAL DESIRE AND HORMONAL IMBALANCE
CONTRACEPTION DUE TO:
★ Estrogen, progesterone, and testosterone all ★ Puberty
play a role in female sexual desire — also ★ Pregnancy
called libido — and sexual functioning.
★ Breastfeeding
★ There’s generally less fluctuation in libido
★ Perimenopause and menopause
if you’re using hormonal birth control
methods, which affect hormone levels. ★ Use of hormonal contraception or
PREGNANCY hormone therapy
★ During the luteal phase of your cycle, the
rise in progesterone prepares your uterus to Hormonal imbalance can sometimes be a
receive a fertilized egg. sign of:

58
 • Polycystic ovarian syndrome
(PCOS). This is the most common SELECTIVE ESTROGEN RECEPTOR
endocrine disorder among young MODULATORS
females. PCOS can cause irregular Selective estrogen receptor modulators, called
menstrual cycle and interfere with SERMs for short, block the effects of estrogen
fertility. in the breast tissue. SERMs work by sitting in
• Androgen excess. This is an the estrogen receptors in breast cells. If a
overproduction of male hormones. This SERM is in the estrogen receptor, there is no
can cause menstrual irregularities, room for estrogen and it can't attach to the cell.
infertility, acne and male pattern Cells in other tissues in the body, such as bones
baldness. and the uterus, also have estrogen receptors.
• Hirsutism. This is an increase in hair But each estrogen receptor has a slightly
growth on the face, chest, abdomen, and different structure, depending on the kind of
back. It’s caused by excessive male cell it is in. So breast cell estrogen receptors are
hormones and can sometimes be a different from bone cell estrogen receptors and
symptom of PCOS. both of those estrogen receptors are different
from uterine estrogen receptors.
Underlying conditions include:
★ Hypogonadism, which is a shortage of TAMOXIFEN Mechanism of Action:
female hormones Tamoxifen competitively
Tamoxifen in inhibits estrogen binding
★ Miscarriage or abnormal pregnancy
pill form (also to its receptor, which is
★ Multiple pregnancy (having twins, called tamoxifen critical for it's activity in
triplets, or more) citrate; brand breast cancer cells.
★ Ovarian Tumor name: Tamoxifen leads to a
Nolvadex) and decrease in tumor growth
See your doctor as soon as you can if you’re in liquid form factor α and insulin-like
experiencing: (brand name: growth factor 1, and an
Soltamox) increase in sex hormone
★ Morning sickness or other signs of
binding globulin. The
pregnancy increase in sex hormone
★ Decreased sexual desire binding globulin limits
★ Vaginal dryness or pain during sex the amount of freely
★ Skipped periods or available estradiol. These
increasingly irregular cycles changes reduce levels of
factors that stimulate
★ Difficulty conceiving tumor growth.
★ Pelvic pain
★ Hair loss or hair growth on your face or Therapeutic Uses:
trunk Indicated to treat estrogen
receptor positive
★ Depression after giving birth
metastatic breast cancer
★ Prolonged menopause symptoms that in adults, as an adjuvant
interfere with your life in the treatment of early
59
 stage estrogen receptor steroid nuclear hormone
positive breast cancer in receptors, Estrogen
adults, to reduce the risk Receptor alpha (ERα) or
of invasive breast cancer Estrogen Receptor beta
after surgery and (ERβ).
radiation in adult women
with ductal carcinoma in Therapeutic Uses:
situ. Indicated for the
prevention and treatment
Adverse Effect: of osteoporosis in
• Menopause-like postmenopausal women,
symptoms, including as well as prevention and
hot flashes, night treatment of
sweats and vaginal corticosteroid-induced
dryness. bone loss.
• Weight gain (more
common) or fluid
retention (edema). Indicated for the
• Irregular or loss of reduction in the risk of
menstrual periods. invasive breast cancer in
• Leg swelling. postmenopausal women
• Nausea. with osteoporosis or
• Vaginal discharge. postmenopausal women
• Skin rash. with a high risk for
• Erectile dysfunction. invasive breast cancer.
• Fatigue.
• Headaches. Adverse Effect:
• hot flashes,
Mechanism of Action: • increased
Acts as both an estrogen sweating,
agonist and antagonist via • headache,
differential effects on the • dizziness,
tissue-specific estrogen • spinning
receptors. Based on the sensation,
findings of competitive • leg cramps or leg
EVISTA pain,
binding assays, evista
displays binding affinity • joint pain,
Chemical name:
that is similar to that of • nausea,
raloxifene
estradiol, the predominant • vomiting,
circulating estrogen. • stomach pain, or
Estrogens play variable • Runny or stuffy
roles at different tissues nose.
in females, including the • Evista may
bone, breasts, uterus and infrequently cause
liver, by binding to the stroke or serious
60
 blood clots to • bone pain
form in the legs, • skin redness or
lungs, or eyes. rash
FARESTON Mechanism of Action: • dry skin
Fareston is a nonsteroidal • hot flashes
Chemical name: triphenylethylene • sweating
Toremifene derivative. Fareston binds • nausea
to estrogen receptors and • mood swings
may exert estrogenic, • vaginal discharge
antiestrogenic, or both or bleeding
activities, depending upon • vision problems
the duration of treatment, • dry eyes
animal species, gender, • dizziness
target organ, or endpoint • swelling of the
selected hands, feet,
ankles, or lower
Therapeutic Uses: legs
For the treatment of • endometrial
metastatic breast cancer cancer
in postmenopausal
women with estrogen BENEFITS OF SERMS
receptor-positive or Because tamoxifen is the most commonly used
receptor-unknown SERM, most of the studies comparing SERMs
tumors. Fareston is
to aromatase inhibitors have looked at
currently under
tamoxifen versus aromatase inhibitors. Several
investigation as a
preventative agent for studies have compared tamoxifen with
prostate cancer in men aromatase inhibitors to see which type of
with high-grade prostatic medicine was more effective in treating early-
intraepithelial neoplasia stage, hormone-receptor-positive breast cancer
and no evidence of in postmenopausal women.
prostate cancer.
BASED ON THE RESULTS, MOST
Adverse Effect: DOCTORS GO BY THE FOLLOWING
• tumor flare RECOMMENDATIONS:
(sudden increase • An aromatase inhibitor is the best type of
in tumor-related
hormonal therapy to start with for
symptoms, such as
postmenopausal women.
bone pain, lymph
node swelling, or • Switching to an aromatase inhibitor after
skin rash) taking tamoxifen for 2 to 3 years (for a total
• hypercalcemia of 5 years of hormonal therapy) offers more
(increased calcium benefits than 5 years of tamoxifen.
levels in the • Taking an aromatase inhibitor for 5 years
blood) after taking tamoxifen for 5 years continues
61
 to reduce the risk of the cancer coming CONTRAINDICATIO
back, compared to no treatment after NS & CAUTIONS:
tamoxifen. • Presence of
• You should not take a SERM if you are primary ovarian
breastfeeding, pregnant, trying to get Failure
pregnant, or if there is any chance that you • Thyroid and
adrenal
could be pregnant. These medicines may
dysfunction
cause damage to developing embryos. You
• Ovarian cysts
should use an effective non-hormonal type • Pregnancy
of birth control — such as condoms, a • Breastfeeding
diaphragm along with spermicide, or a non- • Idiopathic uterine
hormonal I.U.D. — while you are taking a bleeding
SERM. • Known allergies
• Thromboembolic
FERTILITY DRUGS diseases
Some women may have difficulty getting • Respiratory
pregnant because their ovaries do not release N diseases
(ovulate) eggs. Fertility specialists may use
Adverse Effect:
medications that work on ovulation to help
• Vasomotor
these women get pregnant. There are two
flushing
common ways these medicines are used: 1) to • Visual changes
cause ovulation in a woman who does not • Abdominal
ovulate regularly, and 2) to cause multiple eggs discomfort
to develop and be released at one time. • Distention &
About 25% of infertile women have problems Bloating
with ovulation. These women may ovulate less • Nausea
often or not at all (anovulation). Ovulation • VomitinG
induction medications can help a woman to • Ovarian
ovulate more regularly, increasing her chance enlargement
of getting pregnant. These medicines, • Breast tenderness
sometimes called “fertility drugs,” may also • Ovarian
overstimulation
improve the lining of the womb or uterus
• Multiple
(endometrium).
pregnancies
CETROTIDE Therapeutic Uses:
(CETRORELI Work either directly to
INDUCTION OF OVULATION
X) stimulate follicles and
Clomiphene citrate (CC) is a selective estrogen
HUMAN ovulation or stimulate the
CHORIONIC hypothalamus to receptor modulator (SERM) that competes for
GONADOTRO inCrease Follicle estrogen receptors within the hypothalamus.
PIN stimulating hormone With the binding of CC to the estrogen
CLOMIPHENE (Fsh) and luteinizing receptors, the hypothalamus receives a signal
MENOTROPI hormone (Lh) levels that circulating estrogen levels are low. This

62
sets the hypothalamus in motion to secrete LH. The results are
more GnRH, thus stimulating the HPO axis. ovarian stimulation,
The GnRH instructs the anterior pituitary gland maturation of the
to release FSH and LH to initiate a response ovarian follicle,
from the ovarian follicles. Estrogen levels ovulation, and
increase in response to FSH and LH, and a development of the
corpus luteum.
follicle becomes dominant, producing the level
of estrogen needed for the LH surge. The LH
surge causes release of an ovum from the Uterine Motility Drugs
dominant follicle. It is important for LH to Uterine motility drugs stimulate uterine
reach a level high enough to produce an contractions to assist labor (oxytocics) or
ovulatory cycle and that the timing of the LH
induce abortion (abortifacients). Tocolytics are
surge be at the height of follicle formation, drugs used to slow uterine activity. Terbutaline,
which is mid-cycle. a beta2 -selective adrenergic agonist, was
widely used off-label as a tocolytic agent to
CLOMIPHENE Pharmacokinetics relax the gravid uterus to prolong pregnancy.
CITRATE (CC)
In 2011 the U.S. Food and Drug
Clomiphene citrate is
Administration (FDA) required a black box
readily absorbed from
the GI tract. It is warning on this drug alerting prescribers to
partially metabolized significant risks in using the drug for this
in the liver and is purpose and stressing that this was not an
primarily excreted in approved indication for the drug. That same
the feces via biliary year, hydroxyprogesterone caproate (Makena)
elimination. CC has a was approved to reduce the risk of preterm
half-life of about 5 birth in women with a single-fetus pregnancy
days. and a history of singleton spontaneous preterm
birth.
Pharmacodynamics It is not approved for use in multiple-fetus
pregnancies. It is a synthetic progestin and has
The mechanism of
the effects and adverse effects of the
action of CC is
unknown, but it is progestins. It is given by IM injection by a
hypothesized that it health care provider once a week, starting
competes with between 16 and 20 weeks of gestation and
estrogen at receptor continuing until the 37th week.
sites. The perception
of decreased OXYTOCICS ADME:
circulating estrogen by 0.2 mg IM or IV, may
the hypothalamus and Methylergonovine repeat q2-4 h; 0.2 mg PO
pituitary gland triggers (methergine) t.i.d. during the
the negative feedback Oxytocin (Pitocin) peurperium for up to 1
response that increases wk
secretion of FSH and
63
 1-2 mU/min IV through respond to other therapy
infusion pump, increase
as needed, do not exceed A prostaglandin used for
20 mU/min; 10 units IM evacuation of the uterus;
after delivery of the stimulation of cervical
placenta; ripening before labor
ADME:
One spray in each nostril 20 mg vaginal
2-3 min before suppository, may repeat
breastfeeding q3-5 h as needed for
termination of
Therapeutic uses: pregnancy; 0.5 mg gel
Promotion of postpartum via cervical catheter,
DINOPROSTON
uterine involution; repeated in 6 h if needed
E
stimulation of last stage for cervical ripening,
(cervidil, propedil,
of labor, induction of then wait 6-12 h before
gel, prostin E2)
labor; promotion of using oxytocin
uterine contractions
postpartum; used nasally Therapeutic Uses:
to stimulate milk “let A prostaglandin used for
down” in lactating evacuation of the uterus;
women; also being stimulation of cervical
evaluated as a diagnostic ripening before labor
agent to test abnormal ADME:
fetal heart rates (oxytocin 600 mg PO as a single
challenge) and to treat dose; if pregnancy not
breast engorgement terminated by day 3, 400-
ADME: mcg misoprostol PO; If
250 mcg IM at intervals not terminated by day 14,
of 1.5-3.5 h, not to surgical intervention is
exceed 12 mg total dose; suggested.
250 mcg IM to control
postpartum bleeding, not MIFEPRISTONE Therapeutic uses:
to exceed 2 mg total dose (mifeprex, RU- Approved for use in
486) terminating early
CARBOPROST Therapeutic Uses: pregnancy durinf the first
(hemabate) Stimulates uterine muscle 49 d by acting as an
contraction (similar to antagonist of
labor contractions) for progesterone to stimulate
termination of early uterine activity by sites in
pregnancy; evacuation of the endometrium to
missed abortion; control dislodge or prevent the
of postpartum implantation of any
hemorrhage and uterine fertilized eggs
atony that does not
64
ABORTIFACIENTS dilation of the cervix
ABORTION Expulsion of some
• Abortion is defined as the spontaneous INCOMPLETE products of
or induced termination of pregnancy conception
before fetal viability. Expulsion of all
• In medical practice, abortion occurs in COMPLETE products of
1st trimester, miscarriage in 2nd conception
trimester, and premature labor in 3rd ≥ 2 to 3 consecutive
RECURRENT OR
spontaneous
trimester HABITUAL
abortions
Undetected death of
TYPES OF ABORTION an embryo or a fetus
TYPES DEFINITION MISSED that is not expelled
Abortion before 12 and that causes no
EARLY
weeks gestation bleeding
Abortion between 12 Serious infection of
LATE and 20 weeks the uterine contents
gestation SEPTIC during or shortly
Non induced before or after an
SPONTANEOUS
abortion abortion
Termination of
pregnancy for CRIMINAL ABORTION
INDUCED
medical or elective
reasons Criminal abortion is the induced destruction or
Termination of
expulsion of the fetus from the womb of the
pregnancy because
mother unlawfully that is where there is no
the woman’s life or
health is endangered therapeutic indication for operation
THERAPEUTIC or because the fetus
is dead or has METHODS TO INDUCE CRIMINAL
malformation ABORTION
incompatible with 1. Mechanical violence (general and local)
life 2. Abortifacient drugs
Vaginal bleeding 3. Instruments
occurring before 20
weeks gestation MECHANICAL VIOLENCE
without cervical GENERAL MECHANICAL VIOLENCE
THREATENED
dilation and These methods may act directly on the uterus
indicating that
or act indirectly by promoting congestion of
spontaneous abortion
pelvic organs and causing hemorrhage between
may occur
INEVITABLE vaginal bleeding or uterus and pelvic membranes.
rupture of the
membrane These methods are:
accompanied by 1. Severe pressure over abdomen
65
2. Violent exercise cellular metabolism, and bone and muscle
3. Cupping growth
4. Very hot and cold baths alternatively
TESTOSTERONE
Local mechanical violence  It is the prototype of the androgen
While correcting the retroverted uterus hormones
bimanualy  Testes
 Adrenal Cortex
ABORTIFACIENT DRUGS  In women
 In adult males
Abortifacient, any drug or chemical
preparation that induces abortion Testosterone Levels by Age

THE ABORTIFACIENT DRUGS ARE:

1. ECBOLICS
2. EMMENAGOGUES
3. IRRITANTS OF GENITOURINARY
TRACT
4. IRRITANTS OF THE
GASTROINTESTINAL TRACT
5. DRUGS HAVING POISONOUS EFFECT
ON THE BODY
 Inorganic irritants
 Organic irritants
 Abortion pill f-6103
INSTRUMENTS
The instruments are used for the purpose of:
PHARMACOKINETICS
1. RUPTURE OF MEMBRANES
● 98% of circulating testosterone
2. ABORTION STICK
● 2% unbound
3. AIR INSUFFLATION
● excreted in the urine as glucuronic and
4. ELECTRICITY
sulfuric acid conjugates and its metabolites
5. PASTE
6. SYRINGING
PHARMACODYNAMICS
● Testosterone and dihydrotestosterone act as
Drugs Affecting the Male Reproductive
androgens by way of a single androgen
System
receptor officially designated NR3A
● The manufacture of protein within the
ANDROGEN
target cells results in the buildup of cellular
tissue (anabolism)
Control the development and maintenance of
● As men age, the number of Leydig cells
sexual processes, accessory sexual organs,
decreases, sperm production declines, and
66
 luteinizing hormone (LH) and follicle- Skeletal maturation must be monitored every 6
stimulating hormone (FSH) levels rise. months by radiography of the hand and wrist.
Levels of unbound testosterone are reduced Artificial induction of puberty is undertaken
in older men to one third to one fifth the only after boys reach age 15 to 17 years and
peak value. after hypothalamic and pituitary function has
been assessed. A 4- to 6-month trial of
SECONDARY SEX CHARACTERISTICS androgen therapy is implemented, followed by
• pubic hair growth a similar period of rest for reevaluation. If
• beard and body hair growth prolonged therapy is required, testosterone
• Baldness cypionate is used, 50 to 400 mg IM every 2 to
• deepening of the male voice 4 weeks
• thickening of the skin
• sebaceous gland activity ● Testosterone may be administered buccally,
• increased musculature nasally, transdermally, or parenterally.
• bone development ● A buccal mucoadhesive system is available
• Red blood cell formation. that provides a 30-mg dose every 12 hours.
● Transdermal testosterone (TT) patches
INDICATIONS FOR ANDROGEN achieve adequate serum concentrations
THERAPY when applied to the arm, back, or upper
buttocks
Hypogonadism ● Testosterone gel is applied to clean dry skin
of shoulders or upper arms. It should not be
Male hypogonadism is a defect of the applied to the genitals
reproductive system that results in failure of the ANDROGEN Side effect:
testes to produce testosterone, sperm, or both. • frequent erections or
priapism
2 BASIC TYPE • gynecomastia
PRIMARY HYPOGONADISM • urinary urgency
• Spermatogenesis
 Low testosterone with elevated LH
• abdominal pain
 Impaired testicular function • Nausea
• Insomnia
SECONDARY HYPOGONADISM • diarrhea or
 Low testosterone with low-normal LH constipation
 Impaired hypothalamic or pituatary • hives or redness at the
failure injection site
• increased salivation
Adult men may experience testicular atrophy, • mouth soreness
impotence, decreased libido, decreased bone • increased or decreased
density, loss of muscle mass, hair loss, sexual desire
gynecomastia, fatigue, difficulty concentrating, Adverse effect:
or vasomotor flushing. • Androgen therapy may

67
 cause hypercalcemia include increased
by stimulating bone hematocrit, altered
resorption in thyroid and liver
immobilized patients function tests, and
and those with breast elevated urine 17-
cancer. The drug ketosteroids (a by-
should be discontinued product of the
and appropriate breakdown of
measures instituted if androgens). Rare
signs of hypercalcemia complications of long-
occur; signs include term therapy include
nausea and vomiting, hepatic necrosis,
lethargy, decreased hepatic peliosis
muscle tone, polyuria, (blood-filled cysts),
and increased urine hepatic tumors, and
and serum calcium. leukopenia.

• Virilization refers to Contraindications:

the development of • Androgen therapy is
male secondary sex contraindicated during
characteristics in pregnancy and in
women or individuals with
hypogonadal males. nephrosis or those in
the nephrotic phase of
• Less frequent adverse nephritis; it is also
effects include contraindicated in
dizziness, weakness, patients with
changes in skin color, hypercalcemia,
frequent headaches, pituitary insufficiency,
confusion, respiratory hepatic dysfunction,
distress, depression, benign prostatic
pruritus, allergic skin hyperplasia (BPH),
rash, edema of the prostate cancer, or
lower extremities, history of myocardial
jaundice, bleeding, infarction. Men with
paresthesias, chills, breast cancer are not
polycythemia, muscle treated with
cramps, and sodium androgens, nor are
and water retention women whose breast
• Serum cholesterol may cancer is not estrogen
become elevated dependent.
during androgen • Caution must be
therapy. Other exercised when using
alterations in androgen therapy in
laboratory tests individuals with
68
 hypertension, GONADOTROPIN-REALISING hormone
hypercholesterolemia, (GnRH) or a synthetic analogue such as
coronary artery leuprolide, most effective inhibitor of
disease, renal disease, testosterone synthesis.
or seizure disorder. Ketoconazole an anti fungal drug, has
testosterone-suppressing effects similar to
Drug interactions: those of GnRH analogues.
• Androgens potentiate Flutamide is an oral nonsteroidal
the effects of oral antiandrogen drug used as an anti-hormonal
anticoagulants, agent in the treatment of metastatic prostate
necessitating a cancer.
decrease in
Finasteride a synthetic compound inhibits
anticoagulant dosage.
conversion of testosterone to DHT.
Androgens antagonize
calcitonin and
parathyroid hormones
ANTIANDROGENS
• Concurrent use of
corticosteroids GOSERELIN
Inhibits gonadotropin
exacerbates the edema ACETATE
release, suppressing
that can occur with LEUPROLIDE
levels of testosterone
androgen therapy. ACETATE
Barbiturates, Inhibits testosterone
KETOCONAZOLE
phenytoin, and synthesis
phenylbutazone Blocks conversion of
decrease the effects of FINASTERIDE testosterone to
androgens. dihydotestosterone
FLUTAMIDE Androgen receptor
BICALITAMIDE inhibitors
Anabolic steroids
• anabolic steroids, or anabolic- androgenic
Drugs for Treating Penile Erectile
steroids (aass), are a class of steroid
Dysfunction
hormones related to the hormone
testerones.
Sexual Dysfunction
• it has androgenic and virilizing properties
Sexual dysfunction is the inability to
• two steroids that have gained popularity are
experience sexual desire, erection, ejaculation,
human chorionic gonadotropin (hcg) and
and/or detumescence.
tetrahydrogestrinone (thg)
 Androgen deficiency
 Affective disorders
ANTIANDROGENS  Discord in the sexual relationship
 Certain drugs
Antiandrogens or androgen antagonist block
the synthesis or action of androgens. Ejaculatory dysfunction
Impaired ejection of seminal fluid from the
male urethra, can be psychogenic or a result of
69
drug therapy, androgen deficiency, or
sympathetic degeneration. CONTRAINDICATIONS

Erectile dysfunction o Nitroglycerin and other nitrate drugs

Is the inability to achieve or maintain an o Patients with significant
erection satisfactory for sexual performance. cardiovascular
ED happens when not enough blood flows to o Individuals who have anatomic
the penis during sexual stimulation. deformities
 Papaverine FACTS
 Phentolamine  Grapefruit
 prostaglandin E  Amyl nitrate
 nitroglycerin.  Cantharides

A class of drugs called phosphodiesterase Complementary and Alternative Medicine

inhibitors facilitate erection by enhancing
blood flow to the penis. To self-treat sexual problems or to enhance
sexual performance, consumers use a wide
PDE-5 inhibitors currently approved by the variety of herbs and plant-derived compounds
FDA
 Sildenafil  Pausinystalia yohimbine
 Tadalafil  Muira puama
 Vardenafil  Panax quinquefolius
 Avanafil  Lepidium meyenii
 Ginkgo biloba
Phosphodiesterase-5 Inhibitors for Erectile  Mandia whitei
Dysfunction  Saw palmetto
 Tribulus terrestris

70
 PHARMACOLOGY
DRUGS AFFECTING BLOOD PRESSURE (ANTIHYPERTENSIVES)

HYPERTENSION – the most common  Calcium channel blockers

condition leading to myocardial infarction DIURETICS
(MI), stroke, renal failure and death  Promote sodium depletion, which
ESSENTIAL HYPERTENSION – The most decreases extracellular fluid volume
common type of hypertension and affects 95% (ECFV).
of persons with high BP. Contributing factors  First line drug for treating mild
may include hyperlipidemia, African American hypertension
race, diabetes, aging, stress, excessive alcohol HYDROCHLOROTHIAZIDE
ingestion, smoking, obesity, and family history  Most frequently prescribed diuretic for
of hypertension controlling mild hypertension by
SECONDARY HYPERTENSION - 30% of decreasing excess fluid volume.
hypertension cases are attributable to obesity.  Can be used alone for recently
5% of hypertension cases are related to renal diagnosed mild hypertension or can be
and endocrine disorders. used with antihypertensive drugs.
PHYSIOLOGIC RISK FACTORS THIAZIDE DIURETICS
 Diet in high saturated fat and simple  Not recommended for patient with renal
carbohydrates insufficiency (creatinine clearance <30
 Carbohydrates intake can sympathetic mL/min)
nervous activity.  Single thiazide drug, a combination of
 Alcohol increases renin secretion, potassium wasting and potassium-
causing the production of angiotensin II sparing diuretics may be useful; less
 Obesity potassium excretion would occur.
 Normal weight loss can decrease  Can combined to antihypertensive drug
hypertension, but mild to moderate to increase their effectiveness
sodium restriction LOOP DIURETICS (high ceiling)
INITIAL DRUG - First prescribed for  Furosemide, recommended because
hypertension. they do not depress renal blood flow.
6 CATEGORIES OF  Not used in if hypertension is the result
ANTIHYPERTENSIVE DRUGS of RAAS involvement because they
 Diuretics tend to immediately elevate serum renin
 Sympatholytic (Sympathetic level.
depressants) SYMPATHOLYTICS (sympathetic
 Direct-acting arteriolar vasodilators depressants)
 ACE inhibitors  Beta adrenergic blockers
 Angiotensin II-receptor blockers  Centrally acting alpha 2 agonist
(ARB’s)  Alpha-adrenergic blockers
 Direct renin inhibitors

71
  Adrenergic neuron blockers constipation/diarrhea,
(peripherally acting sympatholytic) dyspnea, visual
 alpha 1−¿∧beta blockers¿
impairment
1−adrenergic

BETA ADRENERGIC BLOCKERS ATENOLOL Uses: hypertension,

CARDIOSELEC angina, prophylaxis,
 Called beta blockers
TIVE BETA 1 treatment of AMI
 Used as antihypertensive drugs or in SE: hypotension, heart
combination with diuretics. failure, bradycardia,
 Used in antianginals and fatigue, dizziness, nausea,
antidysrhythmics diarrhea, cool extremities,
 Beta (β+ and β-) adrenergic blockers edema
reduce cardiac output by diminishing BETAXOLOL Uses: hyperternsion,
the sympathetic nervous system HYDROCHLORI glaucoma
response to decrease basal sympathetic DE SE: headache, dizziness,
tone. With continued use, vascular CARDIOSELEC bradycardia, fatigue,
TIVE BETA1 insomnia, arthralgia,
resistance is diminished, and renin
nausea, chest pain
release
BISOPROLOL Uses: hypertension
 More effective in lowering BP in FUMARATE SE: dizziness, headache,
patients who have elevated serum renin BETA1 fatigue, bradycardia,
level. BLOCKER peripheral edema,
NONSELECTIVE BETA BLOCKERS orthostatic hypotension,
 Ex. Propranolol and carvedilol, inhibit diarrhea, arthralgia
beta1 (heart) and beta2 (bronchial) CARVEDILOL Uses: hypertension, AMI,
receptor ALPHA heart failure
 Heart rate slows, BP decreases BREAKER, SE: dizziness,
secondary to the decreases in heart rate, NONSELECTIV drowsiness, weakness,
E Β1 AND Β2 orthostatic hypotension,
and bronchoconstriction occurs because
headache, weight gain,
of unopposed parasympathetic tone. diarrhea, bradycardia,
CARDIOSELECTIVE BETA BLOCKERS fatigue, dyspnea,
 They act mainly as beta1- rather than peripheral edema,
the beta2- receptors, and hyperglycemia
bronchoconstriction is less likely occur. METROPROLO Uses: hypertension, acute
 Ex. Acebutolol, atenolol, betaxolol, L myocardial infarction,
bisoprolol and metoprolol. CARDIOSELEC angina, HF
 Partially effective TIVE Β1 SE: bradycardia,
DRUG Uses and consider. hypotension, stroke,
thrombocytopenia,
ACEBUTOLOL Uses: Hypertension and
diabetes mellitus
HYDROCHLORI dysrhythmias
DE SE: dizziness, NADOLOL Uses: hypertension and
CARDIOSELEC headache,fatigue, NONSELECTIV angina
TIVE BETA1 hypotension, bradycardia, E Β1 & Β2 SE: dizziness,
nausea, drowsiness, fatigue,
bradycardia, hypotension,
72
 palpitations, cold provides a 7-day bradycardia, orthostatic
extremities, erectile duration of action. hypotension, pruritus
dysfunction
PINDOLOL Uses: hypertension GUANFACINE Uses: hypertension
NONSELECTIV SE: dizziness, fatigue, HYDROCHLORI SE: drowsiness, dry
E Β1 &Β2 visual impairment, DE mouth, headache,
myalgia, edema, dizziness, fatigue,
bradycardia, dyspnea, Similar effects to weakness, anorexia,
hypotension, weakness clonidine. abdominal pain,
PROPRANOLOL Uses: hypertension, AMI, constipation, diarrhea,
NONSELECTIV angina, HF, has long half-life erectile dysfunction,
E Β1 & Β2 dysrhythmias, migraine and usually is taken orthostatic hypotension,
prophylaxis once a day bradycardia
SE: dizziness, visual
impairment, fatigue, METHYLDOPA Uses: hypertension,
bradycardia, cool hypertensive urgency,
extremities, erectile first drug widely emergency
dysfunction, used to control SE: orthostatic
hyperkalemia, seizures, hypertension. hypotension, drowsiness,
agitation in high dose, bradycardia, depression,
methyldopa and dizziness, angina,
clonidine can cause peripheral edema,
CENTRALLY ACTING ALPHA2 sodium and water erectile dysfunction,
AGONIST retention constipation
 Decrease the sympathetic response methyldopa and
from the brainstem to the peripheral clonidine are
vessels. They stimulate the alpha 2 administered with
receptor, which in turn decreases diuretics
sympathetic activity; increases vagus
activity; decreases cardiac output; and
decreases serum epinephrine, ALPHA-ADRENERGIC BLOCKERS
norepinephrine, and renin release.  Alpha blockers resulting in vasodilation
 Has minimal effect on cardiac output and decreases BP.
and blood flow to the kidney.  They help maintain the renal blood
 Ex. Methyldopa, clonidine and flow.
guanfacine.  Useful in treating hypertension in
DRUG Uses and SE patients with lipid abnormalities. They
CLONIDINE Uses: hypertension decrease the VLDL and LDL
HYDROCHLORI SE: fatigue, responsible for the build-up of fatty
DE drowsiness,dizziness, plaques in the arteries (atherosclerosis)
confusion, edema, dry and they also increase HDL levels
Available in mouth, anxiety, nausea,  Safe for patients with diabetes because
transdermal vomiting, constipation, they do not affect glucose metabolism.
preparation that abdominal pain,

73
  Can cause sodium and water retention palpitations, tachycardia,
with edema; therefore diuretics are pancreatitis, elevated
frequently given concomitantly to liver enzymes
decrease fluid accumulation in the TERAZOSIN Uses: hypertension,
extremities. HYDROCHLORI BPH
NONSELECTIVE ALPHA ADRENERGIC DE SE: dizziness,
drowsiness, nasal
BLOCKERS
congestion, headache,
 Should not be given to patients with weakness, nausea,
coronary heart disease because of their orthostatic hypotension,
stimulating effects and resultant palpations, peripheral
increase in myocardial oxygen demand edema, erectile
 Ex. Phenoxybenzamine and dysfunction
phentolamine SELECTIVE ALPHA-ADRENERGIC
SELECTIVE ALPHA ADRENERGIC BLOCKERS
BLOCKERS PHENOXYBENZ Uses: hypertension
 Used mainly to reduce BP and can be AMINE associated with
used to treat benign prostatic HYDROCHLORI pheochromocytoma
DE SE: dizziness,
hypertrophy (BPH).
drowsiness, fatigue,
 Ex. Prazosin, terazosin, doxazosin orthostatic hypotension,
PRAZOSIN tachycardia, weakness,
 Commonly prescribed drug gastritis, ejaculatory
 When taken with alcohol or other dysfunction, nasal
antihypertensive drug, the hypotensive congestion
state can be intensified. PHENTOLAMINE Uses: hypertension
TERAZOSIN AND DOXAZOSIN before and after
 Have longer half-lives than prazosin pheochromocytomectom
and they are normally given at bedtime. y, pheochromocytoma
diagnosis, prevention
DRUG Uses and SE
and treatment of IV drug
NONSELECTIVE ALPHA-ADRENERGIC extravasation
BLOCKERS SE: dental pain,
DOXAZOSIN Uses: hypertension and tachycardia, headache,
MESYLATE BPH vomiting, diarrhea,
SE: orthostatic abdominal pain,
hypotension, headache, paresthesias
dizziness, fatigue,
edema, weakness,
ADRENERGIC NEURON BLOCKERS
palpitations, visual
impairment, erectile (peripherally acting sympatholytic)
dysfunction  Potent antihypertensive drugs that block
PRAZOSIN Uses: hypertension norepinephrine release from the
HYDROCHLORI SE: orthostatic sympathetic nerve endings, causing
DE hypotension,

74
 decrease in norepinephrine release that therefore BP is lowered, and pulse rate
results in lowering BP. is moderately decreased.
 A decrease occurs in both cardiac  By blocking the cardiac beta1 receptor,
output and peripheral vascular both heart rate and AV contractility are
resistance. decreased.
 Considered as last choices for treatment  Large dose of alpha/beta blockers could
of chronic hypertension because these block beta2-adrenergic receptors, thus
drugs can cause orthostatic increasing airway resistance.
hypotension.  Large dose of labetalol can cause
 Can cause sodium and water retention atrioventicular (AV) heat block.
and can be taken alone or with a  Common side effects: orthostatic
diuretic to decrease peripheral edema. hypotension, GI disturbances,
RESERPINE nervousness, dry mouth, and fatigue.
 Most potent drug, used to control severe DRUG Uses and SE
hypertension. LABETALO Uses: hypertension,
 Orthostatic hypotension, common side L hypertensive emergency,
effect, the patient is advised to rise preeclampsia, eclampsia
slowly from reclining or sitting SE: orthostatic hypotension,
position. dizziness, hyperhidrosis,
erectile/ejaculatory
 Cause vivid dreams, nightmares, and
dysfunction, fatigue, nasal
suicidal ideation congestion, paresthesia,
DRUG Uses and SE nausea, depression
RESERPINE Uses: hypertension
SE: dizziness, drowsiness, DIRECT-ACTING ARTERIOLAR
depression, dyspnea, VASODILATORS
hearing loss, hypotension,
bradycardia,  Act by relaxing the smooth muscles of
erectile/ejaculatory blood vessels, mainly the arteries,
dysfunction, causing vasodilation.
pseudoparkinsonism  Promote an increase in blood flow to
the brain and kidney.
ALPHA1−¿∧BETA 1−¿ ADRENERGIC BLOCKERS ¿ ¿  With vasodilation, the BP decreases and
 Both have the alpha1 and beta1 sodium and water are retained, resulting
receptor. in peripheral edema.
 Labetalol, example of alpha/beta  Diuretics can be given with direct-
blocker acting vasodilator to decrease the
 Blocking the alpha1 receptor causes edema.
vasodilation, which decreases resistance HYDRALAZINE AND MINOXIDIL
blood flow.  Used for moderate to severe (dose-
 The effect of alpha receptor is stronger related) hypertension
than the effect on the beta receptor;  Cause little orthostatic hypotension
because of minimum dilation of the
75
 arterioles. However, reflex tachycardia acts on both headache, palpitations
and release of renin can occur arterial and
secondary to vasodilation and decrease venous vessel.
BP.
Hydralazine side effects ANGIOTENSIN-CONVERTING ENZYME
 numerous and include reflex INHIBITORS (ACE)
tachycardia  ACE is inhibited, it in turns inhibits the
 palpitations formation of angiotensin II
 edema (vasoconstrictor) and blocks the release
 nasal congestion of aldosterone. When aldosterone is
block, sodium is excreted along with
 headache
water, and potassium is retained.
 dizziness
 ACE inhibitors can cause little change
 GI bleeding
in cardiac output or heart rate and lower
 lupus-like symptoms
peripheral resistance.
 neurologic symptoms (tingling,
 Used primarily to treat hypertension;
numbness)
also effective in treating heart failure
 Ex. Benazepril, captopril, quinapril,
DRUGS Uses and SE
ramipril, and trandolapril. These drugs
HYDRALAZIN Uses: hypertension,
are used for first-line antihypertensive
E hypertensive urgency and
HYDROCHLOR emergency, preeclampsia, therapy, but thiazide diuretics are
IDE eclampsia recommended by JNC 8.
SE: headache, anorexia,  African American and older adults do
nausea, vomiting, not respond to ACE inhibitors with
diarrhea, tachycardia, desired reduction in BP, but when taken
hypotension, angina, with diuretics, BP will usually be
palpitations lowered.
MINOXIDIL Uses: hypertension and  ACE inhibitors should not be given
alopecia during pregnancy because they reduce
SE: headache,
placental blood flow.
hypotension, tachycardia,
angina, peripheral edema,  For patients with renal insufficiency,
erythema, pericardial reduction of the drug dose.
effusion, excess hair  ACE inhibitors can be administered
growth, precipitate angina with food but except for moexipril,
attack which should be taken on an empty
NITROPRUSSI Uses: hypertensive stomach for maximum effectiveness.
DE urgency and emergency, Side effects
very potent HF  Constant, irritated cough (ACE cough,
vasodilator that SE: confusion, may be relieved upon discontinuance of
rapidly decreases hypotension, bradycardia, drug)
bp tachycardia, restlessness,
 Nausea
flushing, dizziness,
76
  Vomiting LISINOPRIL Uses: hypertension, AMI,
 Diarrhea HF
 Headache SE: orthostatic
hypotension, blurred
 Dizziness
vision, weakness, ,
 Fatigue dizziness, headache,
 Insomnia syncope, cough,
 Serum potassium excess(hyperkalemia) hyperkalemia
 Tachycardia MOEXIPRIL Uses: hypertension
DRUG USES AND SE SE: serum lithium levels
ACE INHIBITORS causing toxicity.
BENAZEPRIL Uses: hypertension Dizziness, diarrhea,
HYDROCHLOR SE: headache, dizziness, fatigue, chest pain,
IDE hypotension, fatigue, palpitations, constipation,
palpitations, peripheral cough, hyperkalemia,
edema, erectile hyponatremia, flushing,
dysfunction, rash, orthostatic
hyperkalemia, nausea, hypotension
constipation, flushing, PERINDOPRIL Uses: hypertension and to
angina ERBUMINE prevent MI
CAPTOPRIL Uses: hypertension, post SE: dizziness, cough,
MI, diabetic neuropathy, headache, weakness, back
HF pain, elevated hepatic
SE: cough, , dizziness, enzymes, orthostatic
hypotension, tachycardia, hypotension,
syncope, anorexia, hyperkalemia
constipation, dyspnea, QUINAPRIL Uses: hypertension, HF
hyperkalemia, HYDROCHLOR SE: dizziness, cough,
hyponatremia, rash, IDE headache, orthostatic
fatigue hypotension, tachycardia,
ENALAPRIL Uses: hypertension, HF hyperkalemia, nausea,
MALEATE SE: orthostatic vomiting, chest pain,
hypotension, dizziness, dyspnea, edema
headache, weakness, RAMIPRIL Uses: hypertension, AMI,
syncope, cough, anorexia, HF, prevention of stroke
hyperkalemia, SE: dizziness, cough,
hyponatremia, rash, headache, orthostatic
tachycardia, palpitations hypotension, palpitations,
FOSINOPRIL Uses: hypertension, HF angina, syncope,
SE: dizziness, cough, weakness, nausea,
headache, weakness, vomiting, hyperkalemia
peripheral edema, rash, TRANDOLAPRI Uses: hypertension, AMI,
hyperkalemia, L HF
palpitations, flushing, SE: dizziness, cough,
orthostatic hypotension syncope, dyspepsia,
77
 bradycardia, hypotension,  ARBs may be used as first-line
hyperkalemia, treatment for hypertension
hypocalcemia, myalgia,  Ex. Losartan, valsartan, irbesartan,
weakness, hyperuricemia candesartan, eprosartan, olmesartan,
COMBINATION OF ACE INHIBITORS azilsartan and telmisartan.
WITH CALCIUM BLOCKERS
 Can be taken with or without food and
BENAZEPRIL Uses: hypertension
are suitable for patients with mild
WITH SE: headache,
AMLODIPINE hypotension, dizziness, hepatic insufficiency.
peripheral edema, Side effects: angioedema
hyperkalemia, cough DRUGS Uses and SE
TRANDOLAPRI Uses: hypertension CANDESARTAN Uses: hypertension,
L AND SE: dizziness, headache, HF
VERAPAMIL blurred vision, cough, SE: dizziness,
hypotension, bradycardia, hypotension,
chest pain, hyperkalemia, hyperkalemia, back
fatigue, constipation, pain,
arthgalgia, edema hyperbilirubinemia,
PERINDOPRIL Uses: hypertension rhinitis,
ARGININE SE: dizziness, cough, pharyngitis,
AND headache, peripheral elevated hepatic
AMLODIPINE edema, tachycardia, enzyme, infection
BESYLATE bradycardia, hypotension, EPROSARTAN Uses: hypertension
chest pain, depression, SE: cough, fatigue,
dyspnea, visual rhinitis,
impairment, constipation, pharyngitis,
hyperkalemia sinusitis,
abdominal pain,
ANGIOTENSIN-II RECEPTOR constipation,
BLOCKERS (ARBs) orthostatic
hypotension
 Similar to ACE inhibitors they prevent
IRBESARTAN Uses: hypertension,
the release of aldosterone, a sodium-
diabetic
retaining hormone. neuropathy,
 They act as RAAS proteinuria
 ARBs block angiotensin II from the SE: dizziness,
angiotensin I (AT1) receptors found in cough, fatigue,
many tissues. orthostatic
 ARB cause vasodilation and decrease hypotension,
peripheral resistance. edema, rhinitis,
pharyngitis,
 ARBs should not be taken during
abdominal pain,
pregnancy and unlike ACE, ARBs do
dyspepsia, pyrosis,
not cause constant, irritated cough diarrhea
LOSARTAN Uses: hypertension,
78
POTASSIUM diabetic cramps, nausea,
neuropathy, diarrhea
proteinuria, prevent NEBIVOLOLVALSA Uses: hypertension
stroke RTAN SE: dizziness,
SE: dizziness, drowsiness,
cough, headache, hypotension,
orthostatic hyperkalemia,
hypotension, syncope, vomiting,
weakness, edema, rash, pruritus,
nasal congestion, erectile dysfunction
pharyngitis, nausea,
infection DRUG Uses and SE
OLMESARTAN Uses: hypertension EPLERENON Uses: hypertension, HF,
MEDOXOMIL SE: dizziness, E AMI
headache, SE: dizziness,
orthostatic bradycardia, fatigue,
hypotension, hyponatremia,
peripheral edema, hypertriglyceridemia,
hypercalcemia, hypercholesterolemia,
sinusitis, diarrhea, cough,
pharyngitis, rhinits hyperkalemia,
TELMISARTAN Uses: hypertension, hyperuricemia, edema
prevent MI and
CVA
DIRECT RENIN INHIBITORS
SE: chest pain,
orthostatic ALISKIREN
hypotension,  Treats hypertension, which binds with
sinusitis, dizziness, renin and causes a reduction of
back pain, edema, angiotensin I, angiotensin II, and
cough, aldosterone levels.
hyperkalemia,  Effective for mild and moderate
diarrhea, infection hypertension
VALSARTAN Uses: hypertension,  Can be used alone or with another
heart failure antihypertensive agent
SE: orthostatic
 When used as monotheraphy, has not
hypotension,
hyperkalemia, proven to be as effective in reducing BP
rhabdomyolysis, in African American population.
elevated hepatic DRUG Uses and SE
enzymes ALISKERI Uses: hypertension
AZILSARTAN Uses: hypertension N SE: hypotension,
SE: orthostatic hyperkalemia, peripheral
hypotension. edema, diarrhea,
Dizziness, fatigue, hyperuricemia, gout,
cough, muscle pharyngitis, cough
79
  Flushing
CALCIUM CHANNEL BLOCKERS  Headache
 Found in myocardium (heart muscle)  Dizziness
and vascular smooth muscle (VSM)  Ankle edema
cells.  Bradycardia
 Also known as Calcium antagonist and  AV block
calcium blockers, which block the DRUGS Uses and SE
calcium channel in VSM, promoting PHENYLALKYLAMINE
vasodilation. VERAPAMIL Uses: hypertension,
 Highly protein bound but have a short angina, dysrthymia
half-life SE: dizziness, headache,
3 GROUPS OF CALCIUM BLOCKERS confusion, fatigue,
DIPHENYLALKYLAMINE orthostatic hypotension,
VERAPAMIL blurred vision, peripheral
 Used to treat chronic hypertension, edema, erectile
dysfunction, nausea,
angina pectoris, and cardiac
constipation
dysrhythmias
BENZOTHIAZEPINE
 Act on the arterioles and the heart DILTIAZEM Uses: hypertension,
BENZOTHIAZEPINE HYDROCHLOR angina, dysrthymia
DILTIAZEM IDE SE: dizziness, headache,
 Act on the arterioles and the heart peripheral edema,
DIHYDROPYRIDINES – largest group of dyspepsia, bradycardia,
calcium channel blockers; most of these are hypotension, weakness,
used to control hypertension. dyspnea, pharyngitis,
NIFEDIPINE rhinitis, infection, fatigue
 Decrease BP in older adults and in DIHYDROPYRIDINES
those with low serum renin values. AMLODIPINE Uses: hypertension, heart
failure
 Nifedipine and verapamil are potent
SE: orthostatic
calcium blockers hypotension,
 In its immediate-release form (10- and bradycardia, chest pain,
20-mg capsules), has been associated tachycardia, palpitations,
with an increased incidence of profound pulmonary edema,
hypotension, MI, and death, especially dyspnea, hyperglycemia
in older adults; therefore only extended- FELODIPINE Uses: hypertension
release preparations of nifedipine are SE: dizziness, headache,
recommended for chronic hypertension. peripheral edema,
 Immediate-release nifedipine is usually palpitations, weakness,
prescribed for acute rises in BP only an hypotension, rash, cough
ISRADIPINE Uses: hypertension
as-needed basis in the hospital setting.
SE: dizziness, headache,
Side effect
palpitations, flushing,
 Reflex tachycardia fatigue, hypotension,
80
 angina, tachycardia,
abdominal pain,
peripheral edema
NICARDIPINE Uses: hypertension,
HYDROCHLOR angina
IDE SE: dizziness, headache,
palpitations, weakness,
flushing, orthostatic
hypotension, angina,
tachycardia, peripheral
edema, nausea, vomiting
NIFEDIPINE Uses: hypertension,
angina
SE: : dizziness,
headache, palpitations,
weakness, flushing, Four chambers of the heart
peripheral edema, Right atrium Receives
nausea, pyrosis, tremor, deoxygenated blood
hypotension, muscle from the circulation
cramps, nasal Right ventricle Pumps blood through
congestion, cough, the pulmonary artery
dyspnea, fatigue to the lungs
NISOLDIPINE Uses: hypertension Left atrium Receives oxygenated
SE: pharyngitis, blood
sinusitis, dizziness, Left ventricle Pumps the blood into
headache, palpitations, the aorta for systemic
flushing, orthostatic circulation
hypotension, 4 valves
tachycardia, peripheral Tricuspid and Pulmonic and aortic
edema, visual mitral (2 (2 semilunar)
impairment, atrioventricular)
hypokalemia
Myocardium Heart muscle,
THERAPY FOR HEART FAILURE surrounds the
ventricles and atria
Pericardium Heart fibrous
covering, which
protect it from injury
and infection
Endocardium Three-layered
membrane that lines
the inner part of heart
chamber
2 coronary arteries

81
 Right coronary artery Left coronary artery is 120/80 mmHg. Arterial blood pressure is
determined by peripheral resistance and cardiac
CONDUCTION OF ELECTRICAL output, which is the volume of blood expelled
IMPULSES from the heart in minute, calculated by
The myocardium can generate and conduct its multiplying the heart rate by the stroke volume.
own electrical impulses. The cardiac impulse The average cardiac output is 4 to 8 L/min.
normally located in the originates in the Stroke volume, the amount of blood ejected
sinoatrial (SA) node posterior wall of the right from the left ventricle with each heartbeat, is
atrium. The SA node is frequently called the approximately 70 mL/beat.
pacemaker because it regulates the heartbeat Three factors--preload, contractility, and
(firing of cardiac impulses), which is afterload-determine the stroke volume. Preload
approximately 60 to 80 beats/min in the normal refers to the blood flow force that stretches the
adult. ventricle at the end of diastole. However, an
increase in preload can increase stroke volume,
The atrioventricular (AV) node, located in the and a decrease in preload can decrease stroke
right side of the interatrial septum, has a volume. Contractility is the force of
continuous posterior tract of fibers called the ventricular contraction, and afterload is the
bundle of His, or the AV bundle. The AV resistance to ventricular ejection of blood,
node has an adult rate of 40 to 60 beats/min. If which is caused by opposing pressures in the
the SA node fails, the AV node takes over as aorta and systemic circulation. If afterload
the pacemaker, thus causing a slower heart increases, stroke volume will decrease, and if
rate; the AV node sends AV impulses to the afterload decreases, stroke volume will
ventricles. These two conducting systems, the increase. Specific drugs can increase or
SA and nodes, can act independently of each decrease preload and afterload, affecting both
other. The ventricle can contract independently stroke volume and cardiac output. Most
30 to 40 times per minute. vasodilators decrease preload and afterload,
thus decreasing arterial pressure and cardiac
Drugs that affect cardiac contraction include output.
calcium, digitalis preparations, and quinidine
and its related preparations. The autonomic CIRCULATION
nervous system (ANS) and drugs that stimulate There are two types of circulation,
or inhibit it influence heart contraction system
and drugs that stimulate it decrease heart rate. Pulmonary circulation, the heart pumps
deoxygenated blood from the right ventricle
REGULATION OF HEART RATE AND through the pulmonary artery to the lungs. The
BLOOD FLOW pulmonary artery carries blood that has a high
The heart beats approximately 60 to 80 times concentration of carbon dioxide. Oxygenated
per minute in an adult, pumping blood into the blood returns to the left atrium by the
systemic circulation. As blood travels, pulmonary vein.
resistance to blood flow develops, and arterial
pressure increases. The average systemic Systemic circulation, also called peripheral
arterial pressure, known as blood pressure, circulation, the heart pumps blood from the
82
left ventricle to the aorta and into the general Cardiac Glycosides
circulation. Arteries and arterioles carry the  Digitalis use began as early as CE 1200,
blood to capillary beds. Nutrients in the making it one of the oldest drugs. It is
capillary blood are transferred to cells in still used in a purified form.
exchange for waste products, Blood returns to  Digitalis is obtained from the purple
the heart through venules and veins. and white foxglove plant, and it can he
poisonous.
Blood  Digitalis preparations have come to be
 Composed of plasma, red blood cells known for their effectiveness in treating
(RBC; erythrocytes), white blood cells heart failure (HF), also known as
(WBC; leukocytes) and platelets. cardiac failure (CF), and previously
Function: referred to as congestive heart failure
 Provide nutrients including oxygen to (CHF).
the body. HEART FAILURE/PUMP
 Most of oxygen is carried on the FAILURE/CHRONIC HEART FAILURE.
hemoglobin of RBS When the heart muscle (myocardium)
weakens and enlarges, it loses its ability to
RBC pump blood through the heart and into the
 Life span: 120 days systemic circulation.

WBC ACUTE HEART FAILURE

 Major defense mechanism of the body When compensatory mechanisms fail and
and act by engulfing microorganisms. the peripheral and lung tissues are
 Produce antibodies congested
 Life span : 2 to 24 hours
The causes of HF include chronic
Platelets hypertension, MI, coronary artery disease
 Large cells that cause blood to (CAD), valvular heart dis-ease, congenital
coagulate heart disease, and arteriosclerosis. HF can
be left-sided or right-sided. The patient has
LABORATORY TEST TO DIAGNOSE left-sided HF when the left ventricle does
HEARY FAILURE not contract sufficiently to pump the blood
returned from the lungs and left atrium out
Atrial Natriuretic Hormone or Peptide through the aorta into the peripheral
circulation; this causes excessive amounts
Reference values: 20 to 77 pg/mL; 20 to 77 of blood to back up into the lung tissue.
ng/L (SI units) Usually the patient has shortness of breath
(SOB) and dyspnea.
AGENTS USED TO TREAT HEART
FAILURE Right-sided HF occurs when the heart
does not sufficiently pump the blood
returned into the right atrium from the
83
 systemic circulation. As a result, the blood 1. A positive inotropic action increases
and its constituents are backed up into myocardial contraction stroke volume
peripheral tissues, causing peripheral 2. A (negative chronotropic action
edema. decreases heart rate
3. A negative dromotropic action decreases
Left-sided HF may lead to right-sided HF conduction of heart cells.
and vice versa. Myocardial hypertrophy
resulting in cardiomegaly, increased heart The increase in myocardial contractility
size, can be a major problem associated strengthens cardiac, peripheral, and kidney
with chronic HF. In the cardiac physiology function by enhancing cardiac output,
of HF, an increase in preload and afterload decreasing preload, improving blood flow
occurs. The increased preload results from to the periphery and kidneys, decreasing
an excess of blood volume in the ventricle edema, and promoting fluid excretion. As a
at the end of diastole. This occurs because result, fluid retention in the lungs and
of a pathologic increase in the stretching extremities is decreased. Digoxin does not
and thickening of the ventricular walls, prolong life; rather, it acts by increasing the
which allows a greater filling pressure force and velocity of myocardial systolic
associated with a weakened heart. contraction. Digoxin is a secondary drug
Increased afterload is an additional pressure for HF. First-line drugs used to treat acute
or force in the ventricular wall caused by HF include intravenous (IV) inotropic
excess resistance in the aorta. This agents (dopamine and dobutamine) and
resistance must be overcome to open the phosphodiesterase (PDE) inhibitors, such as
aortic valve so blood can be ejected into the mil-rinone. Other drugs prescribed for HF
circulation. include oral diuretics, beta blockers,
angiotensin-converting enzyme (ACE)
In the early stage of HP, there are no inhibitors, angiotensin-receptor blockers
symptoms, and no structural heart damage (ARBs), calcium channel blockers (CCBs),
occurs. Naturally occurring cardiac and vasodilators, all of which are more
glycosides are found in several plants, convenient to self-administer. Oral
including Digitalis. administration allows the patient to go
home on these medications. Cardiac
DIGITALIS GLYCOSIDES glycosides are also used to correct atrial
This group of drugs inhibits the sodium- fibrillation, cardiac dysrhythmia with rapid
potassium pump, which results in an uncoordinated contractions of atrial
increase in intracellular sodium. This myocardium, and atrial flutter, cardiac
increase leads to an influx of iceanIcaium, dysrhythmia with rapid contractions of 200
which causes the cardiac muscle fibers to to 300 beats/min. This is accomplished by
contract more.etfi c the negative chronotropic effects
(decreased heart rate) and negative
Digitalis preparations have three effects on dromotropic effects talis (decreased
heart muscle: conduction through the atrioventricular
(AV) node).
84
 of digoxin toxicity should be reported
Digitalis (Digoxin) Toxicity promptly to the health care provider.
Overdose or accumulation of digoxin Digitalis toxicity may result in first-degree,
causes digitalis toxicity. Signs and second-degree. Or complete heart block.
symptoms include anorexia, diarrhea,
nausea and vomiting, bradycardia (pulse PHOSPHODIESTERASE INHIBITORS
rate below 60 beats/min), premature
ventricular con-tractions, cardiac PDE inhibitors are another positive
dysrhythmias, headaches, malaise, blurred inotropic group of drugs given to treat acute
vision, *Jai illusions (white, green, or HE. This drug group inhibits the enzyme
yellow halos around objects), confusion, PDE, which promotes a positive inotropic
and delirium. Older adults are more prone response and vasodilation. A drug in this
to toxicity. group is milrinone lactate. This drug
increases stroke volume and cardiac output
Cardiotoxicity is a serious adverse reaction and promotes vasodilation. It is
to digoxin, and ventricular dysrhythmias administered intravenously for no longer
result. ' than 48 to 72 hours. Severe cardiac
dysrhythmias might result from the use of
Three cardiac-altered functions can con- PDE inhibitors, so the patient's
tribute to digoxin-induced ventricular electrocardiogram (ECG) and cardiac status
dysrhythmias: should be closely monitored. Milrinone is a
1. Suppression of AV conduction high-alert medication that may cause
2. Increased automaticity significant harm to a patient when given
3. a decreased refractory period in inappropriately.
ventricular muscle.
Other Agents Used to Treat Heart
The antidysrhythmics phenytoin and Failure
lidocaine are effective in treating digoxin- Vasodilators can he used to treat HF. The
induced ventricular dysrhythmias. vasodilators decrease r take venous blood
Lidocaine should be limited to short-term return to the heart and result in a decrease
treatment. in cardiac nary filling, ventricular
stretching (preload), and oxygen demand
ANTIDOTE FOR on the heart. Arteriolar dilators act in three
CARDIAC/DIGITALIS GLYCOSIDES ways: they (1) reduce cardiac afterload,
which increases cardiac output; (2) dilate
Digoxin- immune Fab may be given to treat the arterioles of the kidneys, which
severe digitalis toxicity. This agent binds improves renal perfusion and increases
with digoxin to form complex molecules fluid loss; and (3) improve circulation to-
that can be excreted in the urine; thus the skeletal muscles.
digoxin is unable to bind at the cellular site ACE inhibitors are usually prescribed for
of action. Serum digoxin levels should be HE ACE inhibitors dilate venules and
closely monitored, and signs and symptoms arterioles, which improves renal blood flow
85
and decreases blood fluid volume. ACE blockers (carvedilol, metoprolol, and
inhibitors also moderately decrease the bisoprolol) have been shown to improve
release and of aldosterone, which in turn cardiac performance. Doses should be low
reduces sodium and fluid retention. ACE initially and gradually increased. It may
inhibitors can increase potassium levels, so take 1 to 3 months for a beneficial effect to
serum potassium levels should be develop.
monitored, especially if potassium-sparing
diuretics such as spironolactone are being Nesiritide is an atrial natriuretic peptide
taken concurrently. Angiotensin II-receptor hormone that inhibits antidiuretic hormone
blockers (ARBs) such as valsartan and (ADH) by increasing urine sodium loss. Its
candesartan have been to a approved for HF effect in correcting HF is achieved by
in patients who cannot tolerate ACE promoting vasodilation, natriuresis, and
inhibitors. antidiuresis. It is useful for treating patients
who have acute decompensated HF with
Diuretics are the first-line drug treatment dyspnea at rest or who have dyspnea with
for reducing fluid volume. They are little physical exertion.
frequently prescribed with digoxin or other
agents. ANTIANGINAL DRUGS
 Used to treat angina pectoris, a
Spironolactone, a potassium-sparing condition of acute cardiac pain caused
diuretic, is used in treating moderate to inadequate blood flow to the
severe HF. Aldosterone secretions are myocardium due to either plaque
increased in HF. This promotes body loss occlusions within or spasms of the
of potassium and magnesium needed by the coronary arteries. With decreased
heart and increases sodium and water blood flow, here is a decrease in oxygen
retention. Spironolactone blocks the to the myocardium, which results pain.
production of aldosterone. This drug
Improves heart rate variability and Anginal Pain
decreases myocardial fibrosis by its  Frequently described by the patient as
cardioprotective effect of emerge blocking tightness, pressure in the center of the
aldosterone in the heart and blood vessels chest, and pain radiating down the left
to promote cardiac remodeling. The arm.
recommended dose for HP is 12.5 to 25  Last for only few minutes
mg/day. Occurrence of hyperkalemia
(excess serum potassium) is rare unless the TYPES OF ANGINA PECTORIS
patient is receiving 50 mg/day and has renal  Classic (stable) angina – occurs with
insufficiency. However, the serum predictable stress or exertion
potassium level should be closely  Unstable (preinfarction) angina –
monitored. In the past, all beta blockers occurs frequently with progressive
were contraindicated for patients with HF severity in related to activity and is
because this drug class reduces cardiac predictable regarding stress/exertion
contractility. With dosage control, beta and intensity
86
  Variant (prinzmetal, vasospastic) Defined as any deviation from the normal rate
angina or pattern of the heart beat
o occurs during test
Includes heart rates that are:
The first two types are caused by narrowing or  Too slow (bradycardia)
partial occlusion of the coronary arteries.  Too fast (tachycardia)
NONPHARMACOLOGIC MEASURES TO  Irregular
CONTROL ANGINA CARDIAC ACTION POTENTIALS
 Proper Nutrition Five phases:
 Adequate Rest Phase 0 – rapid depolarization
 Relaxation Techniques Phase 1 – initial repolarization
 Moderate exercise after consulting with Phase 2 – plateau
health care provider Phase 3 – rapid repolarization
Phase 4 – resting membrane potential between
AVOID: heartbeats
 Heavy Meals
 Smoking TYPES OF ANTIDYSRHYTHMIC DRUGS
 Extreme Weather Changes Class I Sodium channel blockers: IA, IB, IC
Class II Beta blockers
 Strenuous Exercise
Class III Potassium channel blockers
 Emotional Upset
Class IV Calcium channel blockers
TYPES OF ANTIANGINAL DRUGS
MECHANISMS OF ACTION
1. Nitrates
 Blocks adrenergic stimulation of the heart
➜ It is the first agents used to relieve
angina.  Depresses myocardial excitability and
2. Beta Blocker contractility
➜ Beta blockers are effective as  Decreases conduction velocity in cardiac
antianginals because by decreasing the tissue
heart rate and myocardial contractility  Increases recovery time of myocardium
they reduce the need for oxygen  Suppresses automaticity
consumption and consequently reduce
anginal pain. TYPES OF ANTIDYSRHYTHMIC DRUGS
3. CCBs
➜ CCBs relax coronary artery spasm TYPES ACTION
(variant angina) and relax peripheral CLASS I SODIUM Decreases sodium
arterioles (stable angina), decreasing CHANNEL influx into cardiac
cardiac oxygen demand. BLOCKERS cells
ANTIARRYTHMIC DRUGS CLASS II BETA Decrease conduction
BLOCKERS velocity,
automaticity, and
CARDIAC DYSRHYTHMIA
recovery time
(refractory period)
87
CLASS III Prolong dyspepsia, vomiting,
POTASSIUM repolarization during abdominal pain and
CHANNEL ventricular diarrhea
BLOCKERS dysrhythmias QUINIDINE Mode of action:
CLASS IV Prevents calcium SULFATE Its effects in fast
CALCIUM from entering the inward sodium
CHANNEL cells of the heart and current is known as a
BLOCKERS arteries “use-dependent
block”
CLASS IA: SODIUM CHANNEL Therapeutic use:
BLOCKERS For atrial,
DISOPYRAMIDE Mode of Action: ventricular, and
PHOSPHATE It inhibits the fast supraventricular
inward sodium dysrhythmias
current Adverse effect:
Headache, dizziness,
Therapeutic uses: fatigue, weakness,
For ventricular palpitations, fever,
tachycardia nausea, vomiting,
esophagitis, pyrosis,
Adverse effects: diarrhea, and rash
Dizziness, headache, CLASS IB: SODIUM CHANNEL
fatigue, blurred BLOCKERS
vision, dry mouth LIDOCAINE Mode of action:
and skin, urinary Lidocaine blocks
retention/urgency, cardiac sodium
nausea, flatulence, channels shortening
abdominal pain and the action potential
constipation Therapeutic use:
PROCAINAMIDE Mode of action: For ventricular
HYDROCHLORID Works by slowing dysrhythmias
E the nerve impulses in Adverse effects:
the heart and Erythema, pruritus,
reducing the edema, injection site
sensitivity of heart reaction, petechiae,
tissues. dizziness, nausea,
and vomiting
Therapeutic use: MEXILETINE Mode of action:
For ventricular HYDROCHLORID Inhibits the inward
tachycardia and E sodium current,
cardiopulmonary reducing the rate of
resuscitation rise of the action
potential
Adverse effect: Therapeutic use:
Anorexia, nausea, For ventricular
88
 dysrhythmias supraventricular
Adverse effects: dysrhythmias
Weakness, nausea, Adverse effects:
pyrosis, vomiting, Dizziness, fatigue,
diarrhea, tremor, headache, anxiety,
dizziness, headache, dyspnea, dysgeusia,
blurred vision, nausea, vomiting,
palpitations, chest constipation,
pain, and ataxia weakness, edema,
CLASS IC: SODIUM CHANNEL infection influenza,
BLOCKERS and blurred vision
FLECAINIDE Mode of action:
Blocks fast inward CLASS II: BETA BLOCKERS
sodium channels and ACEBUTOLOL Mode of action:
slowly unbinds HYDROCHLOR Acebutulol is a selective
during diastole, IDE (BETA1 β1- receptor
prolonging the BLOCKERS) anatagonist. Acebutulol
refractory period of blocks these β1
the heart receptors, lowering the
Therapeutic use: heart rate and blood
For atrial, pressure
ventricular, and Therapeutic use:
supraventricular Treatment of premature
dysrhythmias ventricular contractions,
Adverse effects: and hypertension
Dizziness, fatigue, Adverse effect:
headache, anxiety, Palpitations,
visual impairment, bradycardia,
tremor, dyspnea, hypo/hypertension,
dysrhythmia tachycardia, chest pain,
exacerbation, hyper/hypoglycaemia,
weakness, chest pain, diabetes mellitus, lupus-
HF, nausea, and like symptoms,
constipation hyperbilirubinemia,
PROPAFENONE Mode of action: dyspnea
HYDROCHLORID Works by slowing Life threatening:
E the influx of sodium Agranulocytosis,
ions into the cardiac thrombocytopenia, HF
muscle cells, causing ESMOLOL Mode of action:
a decrease in (BETA1 Blocks the agonistic
excitability of the BLOCKERS) effect of the
cells sympathetic
Therapeutic use: neurotransmitters by
For atrial, competing for receptors
ventricular, and binding sites
89
 Therapeutic action: headache, palpitations,
Treat atrial flutter, and weakness, nausea,
fibrillation, vomiting, and dyspnea
supraventricular
tachycardia and CLASS III : POTASSIUM CHANNEL
hypertension BLOCKERS
Adverse effect: ADENOSINE Mode of action:
Bradycardia, Agonism of adenosine
hypotension, dizziness, receptors A1 and A2
drowsiness, reduces conduction time
hyperhidrosis, infusion- in the atrioventricular
site reaction, headache, node of the heart
confusion, agitation, Therapeutic use:
and nausea For Paroxysmal
PROPRANOLO Mode of action: supraventricular
L It exerts its response by tachycardia  and Wolff-
HYDROCHLOR competitively blocking Parkinson-White
IDE beta-1 and beta-2 (WPW) syndrome
adrenergic stimulation Adverse effect:
in the heart, which is Headache, dizziness,
typically induced by flushing, dyspnea, chest
epinephrine and pain, hypotension,
norepinephrine anxiety, and paresthesia
Therapeutic uses: AMIODARONE Mode of action:
For atrial and HYDROCHLOR It blocks potassium
supraventricular IDE currents that cause
dysrhythmias repolarization of the
Adverse effect: heart muscle during the
Dizziness, agitation, third phase of the
cold extremities, cardiac action potential,
fatigue, visual increases the duration of
impairment, the action potential as
bradycardia, well as the effective
hyperkalemia, seizures, refractory period for
and erectile dysfunction cardiac cells
SOTALOL Mode of action: (myocytes).
HYDROCHLOR Beta-adrenorecepter Therapeutic use:
IDE blocking For life threatening
Therapeutic use: ventricular tachycardia
For atrial flutter, and and fibrillation
fibrillation and Adverse effect:
ventricular tachycardia Corneal deposits,
Adverse effect: anorexia, nausea,
Bradycardia, HF, vomiting, constipation,
fatigue, dizziness, hypothyroidism,
90
 injection site reaction, fatigue, dizziness,
pneumonitis, headache, palpitations,
photosensitivity weakness, nausea,
DEFETILIDE Mode of action: vomiting and dyspnea
Blocks cardiac ion
channel carrying the CLASS IV: CALCIUM CHANNEL
rapid component of the BLOCKERS
delayed rectifier VERAPAMIL Mode of action:
potassium current HYDROCHLOR inhibits the calcium ion
Therapeutic use: IDE influx through slow
For atrial flutter and channels into conductile
fibrillation and contractile
Adverse effect: myocardial cells and
Headache, dizziness, vascular smooth muscle
insomnia, chest pain, cells
infection, dyspnea, and Therapeutic use:
nausea For angina, cardiac
IBUTILIDE Mode of action: dysrhythmias, and
increases action hypertension
potential duration, Adverse effect:
blocks the rapid Peripheral edema,
component of the constipation, dizziness,
cardiac delayed rectifier fatigue, confusion
potassium current headache, blurred
Therapeutic use: vision, erectile
For atrial flutter and dysfunction,
fibrillation bradycardia, and
Adverse effect: orthostatic hypotension
Headache, palpitations, DILTIAZEM Mode of action:
nausea, tachycardia, inhibits the inflow of
bradycardia, orthostatic calcium ions into the
hypotension, and cardiac, smooth muscle
dysrhythmia during depolarization
exacerbation Therapeutic use:
SOTALOL Mode of action: For angina, Paroxysmal
prolongs the action supraventricular
potential and tachycardia, atrial flutter
refractoriness of cardiac or fibrillation and
tissue hypertension
Therapeutic use: Adverse effect:
For atrial flutter and Headache, peripheral
fibrillation and edema, dizziness,
ventricular tachycardia weakness, bradycardia,
Adverse effect: hypotension, fatigue,
Bradycardia, HF, infection ,dyspnea,
91
 pharyngitis, rhinitis, and
dyspepsia Elevated LDL = greater risk for developing
DIGOXIN Mode of action: atherosclerotic plaques and heart disease.
Inhibits sodium
potassium ATPase, A 12 - 14 hour fasting lipid profile is the test
promoting an increased ordered to determine total cholesterol and
force of cardiac triglyceride concentration in the body.
contraction, cardiac
output, and tissue
Serum Lipid Values
perfusion
Therapeutic use: Lipids Desirable (mg/dL)
For atrial fibrillation Cholesterol 150-200
Adverse effect: Triglycerides 40 - 150
Bradycardia, lipoproteins
hallucinations, bowel LDL <100
necrosis, palpitations HDL >60
DRODENARON Mode of action:
E Works by blocking Elevated cholesterol, triglycerides, and LDL
potassium, sodium, and levels = Risk of CAD
calcium channels and
exhibits antiadrenergic APOLIPOPROTEINS
properties.  Are proteins that bind and transport
Therapeutic use: lipids in the blood
For atrial fibrillation
Adverse effect:
Receptors:
Rash, pruritus, nausea,
diarrhea, vomiting,  ApoA1-HDL
abdominal pain,  ApoB100 – LDL & VLDL
weakness, bradycardia,  ApoB48 – chylomicron remnants
and prolonged QT  ApoE-IDL & chylomicron remnants
interval.
NONPHARMACOLOGIC METHODS
ANTIHYPERLIPIDEMICS  Diets (low fat & cholesterol)
 Drugs that maintain or decrease blood  Exercise (aerobic exercises)
Lipid concentrations.  Don’t smoke
 Therapy is a lifetime commitment
Non-drug therapy should be recommended
Lipoproteins first to lower cholesterol. However,
4 Major Categories: Nonpharmacologic methods will still be
➜ High-Density Lipoprotein (HDL) included in the interventions even if the drug
➜ Low-Density Lipoprotein (LDL) therapy is initiated.
➜ Very-Low Density Lipoprotein (VLDL)
➜ Chylomicrons LIPOPROTEIN PHENOTYPE
TYPE MAJOR LIPIDS
92
 Increased a statin or niacin.
chylomicrons &
I Side effect:
triglycerides
(uncommon)  Constipation
Increased LDL &  Abdominal pain
IIA cholesterol  Bloating
(common)  Vomiting
Increased VLDL,  Diarrhea
LDL, cholesterol, &  Excessive
IIB
triglycerides (very flatulence
common)  Heartburn
Moderately increased  Peptic Ulcer
cholesterol &  Gallstones
III
triglycerides
 Vitamin
(uncommon)
A,D,E,& K
Increased VLDL & Deficiency
markedly increased
IV
triglycerides (very Must be taken with
common) and followed by
Increased sufficient fluids.
chylomicrons, VLDL FIBRATES (fibric Mode of action:
V
& triglycerides acid) Lower blood
(uncommon) triglyceride levels by
 Fenofibrate reducing the liver's
BILE-ACID Mode Of Action: ( hypercholester production of VLDL
SEQUESTRANTS Bile acid olemia) and speeding up the
sequestrants bind  Gemfibrozil removal of
 Cholestyramine bile acids in the (hyperlipoprotei triglycerides from
(One of the first intestine and ns & the blood thus
antihyperlipide increase the hypertriglycerid increasing HDL.
mics) excretion of bile emia)
 Colestipol acids in the stool. Therapeutic Use:
Hydrochloride  Prevents
 Colesevelam Therapeutic Use: pancreatitis &
(First choice  Used for heart attacks.
drug) Hypercholesterol  Used to reduce
emia and is primarily
effective against Hyperlipidemia
Hyperlipidemia type IV and is
type II. also effective for
 Lowers LDL Hyperlipidemia
Cholesterol type II.
levels.  Highly protein-
 Used in bound
combination with
93
 Side effect: side effects and
 Nausea, stomach are given at large
upset, and doses.
sometimes  Used together
diarrhea. with Aspirin
 Liver (following
inflammation. careful drug
 Gallstones when titration and
used for several concomitant)
years.  Available in
 Muscle damage immediate and
when taken slow-release
together with forms.
statin
medications SIDE EFFECTS:
 GI Disturbances
CONTRAINDICA  Elevated serum
TION: Should not liver enzymes
be taken with  Peptic Ulcer
anticoagulants (ex.  Orthostatic
Warfarin) or hypotension
anticoagulant dose  itching
should be reduced.  Flushing (Niacin
Should not be Flush)
combined with  Hyperglycemia
statins.  Hyperuricemia &
Mode Of Action: Gout
Reduces the Should not be given
production of to those with hepatic
proteins that impairment
transport cholesterol Recommended to be
and triglycerides in used only with
the blood. triglyceride levels of
over 500 mg/dL or if
Therapeutic use:
NIACIN (nicotinic intolerant to other
 For treatment.
acid or vitamin B3) Hypercholesterol Mode Of Action:
emia Reduces cholesterol
 Effectively from dietary
decreases VLDL CHOLESTEROL
absorption.
and LDL, ABSORPTION
especially INHIBITORS Therapeutic Uses:
Cholesterol (Ezetemibe)
 For
levels. Hypercholesterol
 Has numerous emia
94
  Acts on the cells enzyme levels.
of the small (ALP, AlT, &
intestines. GGT)
 Can cause a  GIT
small increase in Disturbances
HDL  Rhabdomyolysis
 Usually  Cataract
combined with a Formation
statin.
CONTRAINDICA
SIDE EFFECTS: TIONS
 Diarrhea,  Hepatic Disease
 arthralgia,  Encephalopathy
 abdominal &  Pregnancy &
 back pain, Breastfeeding
 fatigue, ATORVASTATIN Therapeutic Use:
 infection,  Lowers LDL by
 cholelithiasis 43% to 60%
 myalgia  Average Dose:
Therapeutic Uses: 10 -80 mg
STATINS (HMG-  Inhibits  Highly protein
CoA Reductase cholesterol bound (98%)
Inhibitors) synthesis in the Usually
liver. prescribed once
 Atorvastatin  Decreases serum daily.
 Calcium cholesterol,  Half-life = 14
 Pitavastatin LDL, VLDL, and hours
 Rosuvastatin triglycerides.  Excretion: feces
 Pravastatin  Slightly elevate
Sodium HDL. Pharmacodynamics
 Simvastatin  Combined with :
 Fluvastatin other drugs to  Avoid grapefruit
Sodium decrease blood juice.
 Lovastatin pressure and  Taken with no
blood clotting. regard to meals.
COMBINATION:  For  Therapeutic
ANTIHYPERLIPI Hypercholesterol effect
DEMIC DRUGS: emia & effective normally seen
against around 2 to 4
 Amlodipine & Hyperlipidemia weeks.
Atorvastatin Type II.  Peak time: 1 to 2
 Ezetimibe and hours.
Simvastatin Side effect:  Lowers lipids
 Increase liver around 3 to 5
95
 days.  Usually lowered by Vit. B6, B12, and folic
Acid
STATINS Complementary & Alternative  Fast (not eat or drink) for 8–12 hours
Therapies before a homocysteine test.

Black cohosh - may potentiate an increase in High- Sensitivity C-reactive Protein Test
liver enzymes. (hsCRP)
Chinese Skullcap - may increase drug levels  Reference Values: 1 to 3 mg/L.
of Rosuvastatin  The CRP is produced in the liver in
Cranberry - may increase side effects of response to tissue injury or inflammation.
simvastatin.  A valuable test for predicting CAD.
Gingko Biloba - may increase drug levels of  Usually ordered along with cholesterol
statins. screening.
Green Tea - may increase side effects of
 Avoid very strenuous exercise before the
statins.
test.
St. John's Wort - may decrease effect and
 May require fasting
drug levels of statins.
Drugs to Improve Peripheral Blood flow
Miscellaneous Antilipidemics
Peripheral arterial disease (PAD), or
Icosapent Ethyl - decreased lipogenesis in the
Peripheral Vascular Disease (PVD).
liver; and increased plasma lipoprotein lipase
 It is characterized by numbness and
activity.
coolness of the extremities, claudication
Lomitapide - inhibition of the microsomal
(pain and weakness of a limb when
triglyceride transfer protein (MTP).
walking but no symptoms at rest), and
Mipomersen - used to decrease levels of
possible leg ulcers.
cholesterol and other fatty substances in the
blood in people who have homozygous familial  The primary cause is arteriosclerosis
hypercholesterolemia and hyperlipidemia, resulting in
Alirocumab & Evolocumab- human atherosclerosis, which the arteries
monoclonal antibody that binds to proprotein become occluded.
convertase subtilisin kexin type 9 (PCSK9).  Most common in adult

Laboratory Tests Peripheral Vasodilators increase blood flow to

the extremities. They are used in peripheral
Homocysteine Test vascular disorders of venous and arterial
 Reference Values: 4 to 17 mmol/L. vessels. They are more effective for disorders
that result from vasopasm (Raynaud disease)
 Homocysteine is a type of amino acid, a
than from vessel occlusion or arteriosclerosis
chemical your body uses to make proteins.
(arteriosclerosis obliterans, thromboangiitis
 High levels = risk for CVD, Stroke, &
obliterans (buerger disease). In Raynaud
Alzheihmer Disease.
disease, cold exposure or emotional upset can
96
trigger vasopasm from the toes and fingers; NE  Nausea/vomiting
these patients have benefited from vasodilators.  classified as a  Blurred vision
Patients with diabetes mellitus are more likely hemorrheologic  Confusion
to have PAD by two to four times the usual rate agent  Constipation
and are at risk of intermittent claudication  Improves  Cholestasis
microcirculation  Tachycardia
PERIPHERAL VASODILATOR and tissue  Edema
Direct-acting Mode of Action; perfusion by  Hypotension
vasodilator: Acts directly to inhibit decreasing Contraindications:
platelet aggregation blood viscosity
 The drug should
CILOSTAZOL and cause and improving
be taken with
vasodilation, the flexibility of
food, and he
 An especially in femoral erythrocytes,
patient should
antiplatelet vasculature thus increasing
avoid smoking
that has a tissue
because nicotine
dual purpose Therapeutic Uses: oxygenation.
increases
of inhibiting  Peripheral  It inhibits vasoconstriction.
platelet vascular disease aggregation of
 Patients taking an
aggregation  Claudication platelets and red
antihypersensitive
as well as blood cells, and
drug along with
causing Side effect: because it
pentoxyfylline
vasodilation  Dizziness decreases blood
may need to have
to treat  Nausea/vomiting viscosity, it
the
intermittent  Tachycardia helps increase
antihypesensitive
claudication  diarrhea flow through
dosage decreased
peripheral
 Angina to avoid side
vessels.
 Palpitation effects.
 HF
 Orthostatic BLOOD COAGULATION AND
hypotension ANTICOAGULANT
 Peptic ulcer
 Gout Coagulation of Blood
 Diabetes mellitus The process requires coagulation
 Cholelithiasis factors, calcium, and phospholipids.
 Peripheral edema
 Melena During this process, the fibrinogen is converted
 Flushing into fibrin. Fibrin threads get attached to the
 Flatulence loose platelet plug, which plugs the ruptured
 nasopharyngitis part of blood vessels and prevents further blood
loss completely.
Blood viscosity Therapeutic uses:
reducer agent:  Claudication FACTORS INVOLVED IN BLOOD
CLOTTING
PENTOXIFYLLI Side effect:
97
Coagulation of blood occurs through a series of certain clotting factors and these tests are used
reactions due to the activation of a group of to monitor heparin therapy.
substances necessary for clotting are called
clotting factors.  Low Molecular Weight Heparin (LMWH)
Anticoagulants
STEPS OF BLOOD CLOTTING
1. Formation of prothrombin activator Studies have shown that by extracting only the
2. Conversion of prothrombin into low molecular weight fractions of standard
thrombin heparin to depolymerization, the equivalent of
3. Conversion of fibrinogen into fibrin anticoagulation can be achieved with a lower
risk of bleeding.
Anticoagulant
Anticoagulants are given to prevent thrombosis Low-molecular-weight heparin produces a
and used in drawing and storing blood. more stable response at recommended doses.
As a result, frequent laboratory monitoring of
Types of anticoagulants: aPTT is not required because LMWH does not
 Heparin have the standard effect of heparin.
 Low molecular weight heparins (LMWH)
 Oral Anticoagulants (e.g., warfarin) Contraindication:
 Selective Factor Xa Inhibitors LMWHs are contraindicated for patients with
 Direct-Acting Thrombin Inhibitors: stroke peptic ulcers and blood anomalies.
Anticoagulants II (Intravenous) These drugs should not be given to patients
 Anticoagulant Antagonist having eye, brain, and spinal surgery.

HEPARIN Oral Anticoagulants

Heparin introduced in 1938 is a natural Oral anticoagulant inhibits hepatic synthesis of
substance in the liver that prevents clot vitamin k does affect the clotting factors II,
formation. It was first used in blood transfusion VII, IX, and X. Warfarin is an oral
to prevent clotting; heparin is indicated for anticoagulant synthesized from dicumarol.
rapid anticoagulant effect when thrombosis
occurs because of a DVT, PE, or evolving Oral anticoagulants prolong clotting time and
stroke. are monitored by the prothrombin time (PT), a
laboratory test that measures the time it takes
Heparin is poorly absorbed through the blood to clot in the presence of certain clotting
gastrointestinal mucosa and as such is factors which more often affects. International
destroyed by heparinase, a liver enzyme. normalized ratio (INR), is a laboratory test
most frequently used to report PT results.
Partial thromboplastin time (PTT) and
activated partial thromboplastin time (aPTT) Side effects
are laboratory test is to detect deficiencies of Bleeding is the major adverse effect of
warfarin. Patients should be monitored closely
for signs of bleeding such as petechiae,
98
ecchymosis, GI Bleeding, ocular hemorrhage, ● Warfarin use is not recommended
and hematuria. during pregnancy

Drug interactions Direct thrombin inhibitors

Because warfarin is highly protein-bound, it is These drugs interfere with your body’s use of
affected by drug interactions. Aspirin, thrombin, a key enzyme that helps clot your
nonsteroidal anti-inflammatory drugs blood. Though usually injected under the skin,
(NSAIDs), other types of anti-inflammatory you can take it in pill form as dabigatran
drugs can displace warfarin from the protein- (Pradaxa).
bound site and can cause more free-circulating
anticoagulants. Selective factor Xa inhibitors
This type of anticoagulant stops the Xa factor
Pharmacokinetics in the clotting process from working as it
Heparin should. They are approved for the prevention
The half-life of heparin is dose-related: high of DVT and PE.
doses prolong the half-life. The half-life of
heparin is 20 to 60 hours, in contrast to 30 to ANTICOAGULANT DRUG
150 minutes for heparin. Mode of action;
Warfarin Inhibits reactions that
Warfarin has a long half-life and is highly leads to the clotting of
protein-bound, the drug can have accumulative blood and the formation
effects. Bleeding can occur, especially if of fibrin clots both in
another highly protein-bound is administered vitro and in vivo.
together with warfarin.
Therapeutic uses:
 Prophylaxis and
Pharmacodynamics
treatment of venous
Heparin thrombosis and
● The half-life of heparin, administered Anticoagulants pulmonary embolism
for acute thromboembolic disorders, heparin:  Prophylaxis and
prevents thrombus formation and treatment of
embolism. Heparin thromboembolic
sodium complications
● Heparin does not cross the placental
barrier, unlike warfarin. associated with atrial
fibrillation
Side effect:
Warfarin
 Irritation
● Warfarin is effective for long-term
 Pain
anticoagulants therapy. The PT level  Redness or sore at the
should be 1.5 to 2 times the reference injection site
value to be therapeutic, or INR should  Allergic reactions
be 2.0 to 3.0. such as hives
 Chills

99
 
Fever Therapeutic uses:

Increased liver  Prophylaxis and
enzymes on liver treatment of deep
function test results venous thrombosis
MOA: (DVT)
Warfarin and related  PE
vitamin K antagonists Side effects:
(VKAs) block the  Pain
function of the vitamin K  Bruising
epoxide reductase  Redness
complex in the liver  Swelling at the
Therapeutic uses: injection site
 Prophylaxis and Mode of action:
treatment of venous Inhibits free factor Xa
thrombosis and and prothrombinase
pulmonary embolism activity
 Prophylaxis and Therapeutic uses:
treatment of  Prophylaxis and
thromboembolic treatment of deep
complications RIVAROXAB venous thrombosis
WARFARIN associated with atrial AN (DVT)
fibrillation  PE
 Prophylaxis and Side effects:
treatment of  Nosebleeds
thromboembolic  Heavier periods
associated with  Bleeding gums
cardiac valve
 bruising
replacement
Mode of action:
Side effects:
Orally active factor Xa
 Severe bleeding Inhibitors that bind
including heavier than reversibly to the active
normal menstrual site of factor Xa. They
bleeding inhibit both free actor Xa
 Red or brown urine and factor Xa that is
APIXABAN
 Black or bloody stool bound to the
 Severe headache AND prothrombinase complex
 Stomach pain Therapeutic uses:
Mode of action: EDOXABAN Prophylaxis and treatment
Selectively binds to of deep venous
antithrombin III thereby thrombosis (DVT) and
FONDAPARIN
potentiating the innate PE
UX
neutralization of activated Side effects:
factor X (Factor Xa) by  bleeding more easily
antithrombin than normal such as
100
 nosebleeds, heavier injection such as
periods, bleeding redness, swelling or
gums itching
 bruising  hives
Mode of action:
Mode of action: Inhibits reactions that
Factor Xa inhibitors that leads to the clotting of
bind reversibly to the blood and the formation
active site of factor Xa. of fibrin clots both in
They inhibit both free vitro and in vivo.
factor Xa and factor Xa
that is bound to the Therapeutic uses:
prothrombinase complex Prevention and treatment
Therapeutic uses: of venous thrombosis in
Prophylaxis and treatment ENOXAPARI the maternal or placental
BETRIXABAN of venous N SODIUM circulation
thromboembolism (VTE)
Side effects: Side effect:
 nosebleed  nausea
 blood in urine  diarrhea
 major bleeding  fever
 GI bleeding  peripheral edema
 Intracranial  injection site reactions
hemorrhage (rare) (swelling, pain,
 Fatal bleeding (rare) bruising, or redness)
Mode of action: Mode of action:
Binds to antithrombin III Inhibiting thrombin-
and accelerates its catalysed or –induced
inhibition of thrombin reactions, including fibrin
and factor Xa formation
Therapeutic uses:
Therapeutic uses:  treatment of
Low-molecular  Prophylaxis Direct-acting thrombosis in adult
heparin:  DVT thrombin patients with heparin-
 Unstable angina inhibitor: induced
Dalteparin thrombocytopenia
Side effects: ARGATROBA (HIT) or at risk for
 Trouble breathing N HIT undergoing
 Swelling of your percutaneous
throat or tongue coronary intervention
 Itching (PCI)
 Rash  deep venous
 Fever thrombosis (DVT)
and PE treatment
 Reaction at the site of
Side effects:
101
  nausea/vomiting Inhibiting thrombin-
 diarrhea catalysed or –induced
 stomach pain reaction, including fibrin
 fever formation
 headache Therapeutic uses:
 back pain  prevent stroke
Mode of action:  treat deep vein
Inhibiting thrombin- thrombosis(DVT)
catalysed or –induced  pulmonary embolism
reactions, including fibrin (PE) 
N Side effect:
formation
Therapeutic uses:  Acid or sour stomach
 Deep venous  Black, tarry stools.
thrombosis (DVT)  bloody stools
prophylaxis.  pain or burning in the
 Heparin-induced throat
BIVALIRUDI thrombocytopenia  stomach discomfort
N (HIT) with  upset
thrombosis  burning
Side effects:  pain
 Abdominal pain or Mode of action:
swelling. Therapeutic uses:
 Arm, back, or jaw Heparin reversal
pain. Side effect:
 Black, tarry stools.  sudden fall in blood
PROTAMINE
 Blood in the eyes. pressure
SULFATE
 Blood in the urine.  slow heart rate
Mode of action: (bradycardia)
Inhibiting thrombin-  pulmonary
catalysed or –induced hypertension
reaction, including fibrin  shortness of breath
formation PHYTONADI Therapeutic uses:
Therapeutic uses: ONE  For vitamin K
Prophylaxis of deep vein deficiency
thrombosis  Bleeding from
DESIRUDIN Side effect: warfarin toxicity
 Bleeding gums Side effect
 Collection of blood  Temporary flushing
under the skin  taste changes
 Coughing up blood  dizziness
 Difficulty with  rapid heartbeat
breathing or  sweating
swallowing  shortness of breath
DABIGATRA Mode of action:
102
  bluish lips/skin/nails  Thromboembolism, occlusion of an artery
may also rarely occur or vein caused by a thrombus or embolus.
Pharmacokinetics
FIBRINOLYTIC AND ANTIPLATELET
DRUGS The commercial preparation of alteplase is
TERMINOLOGIES! identical to natural human tissue plasminogen
activator (tPA), the enzyme the converts
Fibrinolytic mechanism -The fibrinolytic plasminogen to plasmin.
system functions to remove the clot after the Pharmacodynamics
vasculature is repaired, as well as to degrade
clots that form in the bloodstream.  Alteplase is similar to natural human tissue
plasminogen activator. It promotes
Fibrinolysis – lysis and removal of blood clot
thrombolysis by converting plasminogen to
after stoppage of bleeding and healing of the
plasmin, which degrades fibrin, fibrinogen.
vascular wall.
Alteplase - is a thrombolytic drug, sometimes ANTIPLATELET DRUGS
called a "clot-busting" drug. It helps your body Antiplatelets are used to prevent thrombosis in
produce a substance that dissolves unwanted the arteries by suppressing platelet aggregation.
blood clots. Alteplase is used to treat a stroke Heparin and warfarin prevent thrombosis in the
caused by a blood clot or other obstruction in a veins.
blood vessel.
Antiplatelet drug therapy is mainly for
Ischemia – is a condition in which the blood
prophylactic use in:
flow (and thus oxygen) is restricted or reduced
in a part of the body. 1. Prevention of MI or stroke for patients with
Necrosis - the death of body tissue. It occurs a family history
when too little blood flows to the tissue. 2. Prevention of repeat MI or stroke,
Acute myocardial infarction - is myocardial
necrosis resulting from acute obstruction of a 3. Prevention of stroke for patients having
coronary artery. Symptoms include chest transient ischemic attacks (TIAs)
discomfort with or without dyspnea, nausea, Mode of action:
and diaphoresis. The exact mechanism by
Thromboembolism - the blocking of a blood which anagrelide lowers
vessel by a particle that has broken away from platelet count is unclear.
a blood clot at its site of formation. Evidence from human
trials suggests a dose-
Fibrinolytic drugs ANAGRELIDE related suppression of
 Thrombolytic have been used since the HYDROCHLO megakaryocyte
early 1980s to promote the fibrinolytic RIDE maturation, the cells
mechanism. responsible for platelet
 Thrombolytics should be administered production - blood
within 3 to 4 hours or within 30 minutes drawn from patients
after arriving at the hospital for treatment. receiving anagrelide
showed a disruption to
the post-mitotic phase of
103
 megakaryocyte  Temporary relief of
development and a headache, pain and
subsequent reduction in fever of colds, minor
their size and ploidy. pain of arthritis,
Therapeutic uses: muscle pain,
 thrombocythemia, menstrual pain, and
secondary to toothache.
malignant neoplasms Side effect:
 to reduce platelet  abdominal pain
count and the  nausea
associated risk of Mode of action:
thrombosis. Cilostazol and several of
 Chronic its metabolites are cyclic
myelogenous AMP (cAMP)
leukemia phosphodiesterase III
 Polycythemia vera inhibitors (PDE III
Side effect: inhibitors), inhibiting
 Headache phosphodiesterase
 dizziness activity and suppressing
 palpitations cAMP degradation with
 peripheral edema a resultant increase in
 tachycardia cAMP in platelets and
 abdominal pain blood vessels, leading to
inhibition of platelet
 nausea
aggregation and
 diarrhea
vasodilation.
 weakness CILOSTAZOL Therapeutic uses:
 dyspnea  claudication due to
Mode of action: peripheral vascular
The acetyl group of disease
acetylsalicylic acid binds  PVD
with a serine residue of Side effect:
the cyclooxygenase-1
 Smoking may cause
(COX-1) enzyme,
decrease of serum
leading to irreversible
levels
inhibition. This prevents
 Headache
ASPIRIN the production of pain-
causing prostaglandins.  Nausea
Therapeutic uses:  Nasopharyngitis
• Stroke  Rhinitis
• MI  Dizziness
• TIA  Infection palpations
• atrial fibrillation  Peripheral edema
• Thromboembolism CLOPIDOGRE Mode of action:
prophylaxis. L metabolized to its active
104
 form by valves.
carboxylesterase-1.The  prevention of
active form is a platelet atherothrombotic
inhibitor that irreversibly events in adult
binds to P2Y ADP patients with acute
receptors on platelets. coronary syndrome
This binding prevents Side effect:
ADP binding to  headache
P2Y receptors, activation  dizziness
of the glycoprotein  bleeding
GPIIb/IIIa complex, and  nausea
platelet aggregation.  hypo/hypertension
Therapeutic uses:
 dyspnea
 Thromboembolism
 hyperlipidemia
associated with
 hypercholesterolemia
prosthetic heart
DIPYRIDAMO valves.  epistaxis
LE Mode of action:
 a percutaneous
a P2Y receptor
coronary intervention
antagonist
(PCI) for acute
Therapeutic uses:
coronary syndrome
(ACS)  thromboembolism
prophylaxis
 Stable ischemic heart
disease.  reduce the risk of
cardiovascular death
 Atrial fibrillation.
Side effect:  myocardial infarction
 Dizziness  stroke in patient with
acute coronary
 Headache TICAGRELOR syndrome
 Nausea
Side effect:
 Abdominal pain
 headache
 Dyspnea
 dizziness
 Flushing
 bradycardia
 Chest pain
 bleeding
Mode of action:
 nausea
an thienopyridine and a
prodrug which inhibits  diarrhea
ADP receptors by  cough
irreversibly acting on the  hypo/hypertension
PRASUGREL P2Y12 receptor on  dyspnea
platelets.  Mode of action:
Therapeutic uses: Inhibits platelet
 Thromboembolism aggregation through the
VORAPAXAR
associated with reversible antagonism of
prosthetic heart protease-activated
receptor 1 (PAR-1), also
105
 known as thrombin Combination of antiplatelet drugs
receptor. 
1. Dipyridamole 200mg and aspirin 25mg –
Therapeutic uses:
For stroke prevention, ischemic stroke and
 thrombosis
TIA. May cause headache, nausea, diarrhea,
 MI abdominal pain, dyspepsia, fatigue, bleeding
 PAD and arthralgia.
 Stroke
 reduction of 2.Aspirin (ASA) and omeprazole – For
thrombotic prophylaxis of secondary cardiovascular and
cardiovascular cerebrovascular events. May cause gastritris,
events in patients nausea,diarrhea, anemia, blurred vision,
with a history of bleeding, tinnitus, and hearing loss.
myocardial infarction Other antiplatelet drugs include
(MI) or peripheral anagrelide,clopidogrel, dipyridamole,
arterial disease peasugerel, ticagrelor, vorapaxar, cangrelor,
(PAD) abciximab, eptifibatide and tirofiban, they are
Side effect: known as adenosine diphosphate (ADP)
 bleeding antagonist.
 intracranial/GI
bleeding Clopidogrel is an antiplatelet drug frequently
 anemia used after MI or stroke to prevent a second
Mode of action: event. It may be prescribe singly or with
a selective, reversible, aspirin.
P2Y12 platelet receptor PHARMACOKINETICS
antagonist which inhibits
ADP platelet Clopidogrel is rapidly absorbed and has a high
aggregation. ADP is protein-binding power
typically released by
PHARMACODYNAMICS
damaged blood vessels,
red blood cells, and/or Clopidogrel prevents platelet aggregation by
platelets due to agonists blocking the binding of ADP to the platelet
stimulating platelet ADP receptor.
CANGRELOR activity
Therapeutic uses: RESPIRATORY DRUGS (UPPER
RESPIRATORY)
 prevention of
thrombosis in PCI ANTITUSSIVES
 MI
Side effect: Act on the cough-control center in the medulla
 Bleeding to supress the cough reflex. The cough is a
naturally protective way to clear the airway of
 Dyspnea
secretions or any collected material.
 Hematoma
 Hematuria A sore throat may cause coughing that
 Intracranial bleeding increases throat irritation. If the cough is

106
nonproductive and irritating, an antitussive Important  diarrhea
may be taken. information to know  constipation
The three (3) types of antitussives are about  dependence
nonopioid, opioid, or combination preparations. Codeine:  tolerance
Antitussives are usually used in combination  Keep the  withdrawal
with other agents medication in a  respiratory
place where depression
BLACK BOX WARNINGS others cannot get  euphoria (AE)
Drug exposes patients and other users to the to it.  apathy (AE)
risks of opioid addiction, abuse and misuse,  Do not give this  drowsiness (AE)
which can lead to overdose and death medicine to  relaxation (AE)
anyone younger
A strengthened warning to mothers that than 12 years old, CONTRAINDICA
breastfeeding is not recommended when taking or anyone under TIONS
codeine due to the risk of serious adverse 18 who recently  Hypersensitivity
reactions in breastfed infants. These can had surgery to to codeine
include excess sleepiness, difficulty remove the tonsils  Significant
breastfeeding, or serious breathing problems or adenoids. respiratory
that could result in death.  Taking opioid depression
OPIOID ANTITUSSIVE medicine during  Children
pregnancy may younger than 12
OPIOID ANTITUSSIVE cause life- years
 The most powerful analgesics that can threatening  Postoperative
relieve any type of pain withdrawal pain
 Act mainly at the level of cortex, CNS symptoms in the management in
 Can produce addiction new-born. children (below
Therapeutic Uses:  Never use codeine 18 years) who
For cough and pain. in larger amounts, have undergone
Side Effect: or for longer than tonsillectomy
May cause drowsiness, dizziness, euphoria, prescribed. Tell and/or
blurred vision, weakness, nausea, diarrhea, your doctor if you adenoidectomy
constipation, dependence, tolerance, feel an increased
withdrawal and respiratory depression. urge to take more Contraindicated
CODEINE (CSS II) Therapeutic Use: of this drug:
medicine Alvimopan
Cough
A class of Pain DEXTROMETHOR Mode of action:
medications called PHAN Decreases
opiate (narcotic) Side effect/Adverse excitability of cough
Analgesics and is effects: Often referred to as center in the
used to treat pain, it  Drowsiness DXM, is a medication medulla
works by changing  Dizziness most often used as a
the way the brain and cough suppressant in Therapeutic Use:
 blurred vision
nervous system over-the-counter cold For temporary
 weakness
respond to pain. and cough medicines. cough relief due to
 nausea
107
It is sold in syrup, doctor's advice.
tablet, spray, and Taking a
lozenge forms. stimulant together
with cough
How should this medicine can
medicine be used? especially for non- increase your risk
Dextromethorphan productive cough of unpleasant side
should only be used due to sore throat, effects.
according to the label irritation, or  Do not use any
or package directions. common cold. other over-the-
Do not take more counter cough,
than the Side effect: cold, or allergy
recommended  dizziness medication
amount of without first
 lightheadedness
dextromethorphan in asking your
 drowsiness
a 24-hour period. doctor or
Refer to the package  nervousness
pharmacist.
or prescription label  restlessness
Dextromethorpha
to determine the  nausea/vomiting n is contained in
amount contained in  stomach pain many
each dose. Taking  confusion combination
dextromethorphan in  fatigue medicines
large amounts can  ataxia available over the
cause serious side  psychosis (AE) counter. If you
effects or death  tachycardia (AE) take certain
 seizures (AE) products together
what to avoid  respiratory you may
 Avoid drinking depression (LT) accidentally take
alcohol. It can  serotonin too much of this
increase some of syndrome (LT) medicine. Read
the side effects of the label of any
dextromethorphan Contraindications: other medicine
. This medication  Asthma you are using to
can cause side  Emphysema see if it contains
effects that may dextromethorphan
 tobacco smoking
impair your Therapeutic use:
 Hepatic disease
thinking or Cough and common
reactions.  Children, infants
cold
 Avoid taking diet  Pregnancy
Side effect:
pills, caffeine  Breastfeeding
GUAIFENESIN and  Drowsiness
pills, or other CODEINE (CSS V)  Dizziness
stimulants (such  Headache
as ADHD  Euphoria
medications)
 Hypotension
without your
 Dependence
108
  Nausea/vomiting  Headache
 Constipation  Confusion
 Urinary  Nausea
retention  Constipation
 Respiratory  Ocular irritation
depression
Therapeutic use:
Cough
Side effect: DECONGESTANTS
 Drowsiness Decongestants decrease the overproduction of
 Dizziness secretions by causing local vasoconstriction to
 Headache the upper respiratory tract.
HOMATROPINE  Euphoria
and  This vasoconstriction leads to a
 Headache
HYDROCODONE shrinking of swollen mucous
 Blurred vision membranes and tends to open clogged
(CSS III)
 Dry mouth nasal passages, providing relief from
 Nausea/vomiting the discomfort of a blocked nose and
 Urinary promoting drainage of secretions and
retention improved airflow.
 Constipation
 dependence  Topical nasal decongestants, oral
NON OPIOID ANTITUSSIVES decongestant, and topical steroid nasal
decongestants are classifications of
 Mild analgesics that treat mild types of
decongestants.
pain as headache
 Act at the level of thalamus & CLASSIFICATIONS
hypothalamus
 No addiction Topical nasal decongestants
Therapeutic Use:  Imitate the effects of the sympathetic
For cough nervous system to cause
Side effect: vasoconstriction, leading to decreased
 Drowsiness edema and inflammation of the nasal
 Dizziness membranes.
 Headache
 Relieve the discomfort of nasal
 Confusion
congestion that accompanies the
 Nausea common cold, sinusitis, and allergic
 Constipation rhinitis.
 Ocular irritation
Therapeutic Use:  Dilation of the nares to facilitate
Cough medical examination or to relieve the
Side effect: pain and congestion of otitis media.
BENZONATATE
 Drowsiness Oral decongestants
 Dizziness

109
  Decrease nasal congestion related to the  Caution must be used when there is
common cold, sinusitis, and allergic lesion or erosion in the mucous
rhinitis. membrane that could lead to systemic
absorption.
 Shrink the nasal mucous membrane by
stimulating the alpha-adrenergic  Caution should also be used in patients
receptors in the nasal mucous with any condition that might be
membranes. exacerbated by sympathetic activity.
 This shrinkage results in a decrease in  If used during pregnancy or lactation,
membrane size promoting drainage of caution is advised.
the sinuses and improving airflow.
 Caution should be used in any patient
Topical nasal steroid decongestants who has an active infection, including
tuberculosis because systemic
 The exact mechanism of action of absorption would interfere with the
topical steroids is unknown. inflammatory and immune response.
 Their anti-inflammatory action results Adverse effects
from their ability to produce a direct
local effect that blocks many of the  Rebound congestion - An adverse
complex reactions responsible for the effect that accompanies frequent or
inflammatory response. prolonged use of the drug is a rebound
congestion, technically called rhinitis
Indication medicamentosa.
Topical nasal decongestants  Topical nasal decongestants - Adverse
 Relieves discomfort of nasal congestion effects associated with topical
associated with the common cold, decongestants include local stinging
sinusitis, allergic rhinitis. and burning, which may occur the first
 Relieves pressure of otitis media. few times the drug is used.

Oral decongestants  Oral decongestants - Because this drug

is taken systemically, adverse effects
 Decreases nasal congestion associated related to the sympathomimetic effects
with the common cold, allergic rhinitis. are more likely to occur, including
 Relief of pain and congestion of otitis feelings of anxiety, tenseness,
media. restlessness, tremors, hypertension,
arrhythmia, sweating and pallor.
Topical nasal steroid decongestants
 Topical nasal steroids decongestants
• Treatment of seasonal allergic rhinitis -The most common adverse effects are
in patients who are not obtaining a local burning, stinging, dryness of the
response with other decongestants or mucosa, and headache.
preparations.
Interactions
• Relieves inflammation following
removal of nasal polyps. Cyclopropane or halothane - The use of
topical nasal decongestants is contraindicated
Contraindications and Cautions
110
with concurrent use of cyclopropane or • Many agents can trigger the release of
halothane anesthesia because serious Histamine from Mast cells and Basophil
cardiovascular effects could occur. WBCs:
 OTC products - Many OTC products, • Foreign antigens (“allergens”)
including cold remedies, allergy
medications, and flu remedies may • Certain drugs (ex: morphine,
contain pseudoephedrine; taking many dextran)
of these products concurrently can • Endogenous chemical mediators
cause serious adverse effects. (ex: kinins)
 Acute infections - Because nasal
steroids block the inflammatory
response, their use is contraindicated in • The H1 Receptor Blockers or referred
the presence of acute infections such as to as antihistamine group can be
Candida albicans infection, divided into first and second
tuberculosis, and any airborne generations.
infections (e.g., chicken pox, measles)
because systemic absorption would
interfere with the inflammatory and
immune responses.
ANTIHISTAMINE
• Histamine is synthesized from the amino
acid HISTADINE
• It is present in all tissues but most abundant

1st Generation Antihistamine

Alkylamine Mode of Action:
derivatives: Brompheniramine is
an antagonist of the
BROMPHENIRAM H1 histamine
INE receptors with
moderate
antimuscarinic
actions, as with
other common
antihistamines such
as
diphenhydramine.
Therapeutic Use:
For the treatment of
in Skin, Lungs, and GIT the symptoms of
• Histamine is stored in Mast Cells and  common cold
Basophil WBCs.  allergic rhinitis,
111
 such as runny  difficulty
nose, itchy eyes, concentrating
watery eyes, and  dry mouth
sneezing.  Headaches
Side effect/Adverse  blurred vision
Reaction: Mode of Action:
Due to its H1- Antihistamine
anticholindergic block the H1-
effects may cause: Receptors and also
 drowsiness Acetylcholine
 sedation Receptors in the
 dry mouth CNS
 dry throat (“anticholinergic
 blurred vision action”
 increased heart Therapeutic Use:
rate. 1. Used to treat
Mode of Action: Allergic and
binds to the Inflammatory
histamine H1 Reactions
receptor. This - Allergic
blocks the action of rhinitis
endogenous - Urticaria
Ethanolamine
histamine, which - Burning
Derivatices:
subsequently leads tongue
to temporary relief syndrome
Diphenhydramine
of the negative and
(Benadryl, Diphen,
symptoms brought geographic
Banophen, Genahist)
on by histamine. tongue
Therapeutic Use: 2. Used to treat
- hay fever and prevent
CHLORPHENIRA - red, itchy eyes Motion Sickness
MINE (conjunctivitis) - Beneficial in
- eczema alleviating
- hives (urticaria) vertigo and
caused by food nausea
allergies and - This effect is
chickenpox produced by
insect bites and the anti-
stings cholinergic
Side effect/Adverse action on the
Reaction: CNS
 feeling sick 3. Used as a
(nausea) Sedative
 Sleepy or 4. Used as Cough
dizziness.
112
 Suppressant mild,
Side effect/Adverse uncomplicated
Reaction: allergic skin
 Most due to the manifestations
blocking of Ach of urticaria and
Receptors in the angioedema.
CNS, it can  Used as self-
cause sedation medication for
and fatigue. temporary relief
 Dry mouth and of symptoms
throat associated with
 Nasal stuffiness the common
 Loss of appetite cold.
Contraindications: Side effect/Adverse
1. Patients with Reaction:
Glaucoma - Drowsiness
2. Patients on - dry mouth, nose,
- CNS Depressants and throat
- Sedatives and - Dizziness
Alcohol - decreased
Mode of Action: coordination
a selective - Nausea
histamine H1 - chest congestion
antagonist and binds - Headache
to the histamine H1 - excitement
receptor. This (especially in
blocks the action of children)
endogenous - Nervousness
histamine, which Therapeutic Use:
subsequently leads  Allergy rhinitis
to temporary relief  Pruritus
CLEMASTINE of the negative  urticaria
FUMARATE symptoms brought Side effect/Adverse
on by histamine. Reaction:
Piperidine  dizziness
Therapeutic Use: derivatives:  drowsiness
 For the relief of  dry mouth
symptoms CYPROHEPTADIN
E  excitability
associated with  euphoria
allergic rhinitis,  insomnia
sneezing,
 blurred vision
rhinorrhea,
 restlessness
pruritus and
acrimation.  wheezing
 Management of  hypotension
113
  tachycardia anti-cholinergic
 urinary retention side effects such
Therapeutic Use: as sedation.
 allergic rhinitis Therapeutic Use:
 chronic urticaria One of the most
Side effect/Adverse common uses for this
Reaction: drug is for a condition
 dizziness called allergic rhinitis.
 drowsiness - Seasonal
Allergic Rhinitis
 blurred vision
Piperazine - Perennial
 hypotension
derivatives: Allergic Rhinitis
 tachycardia - Chronic
LEVOCETIRIZINE
 palpitations Urticaria
 fatigue Side effect/Adverse
 nasal congestion Reaction:
 dyspnea - dizziness,
 urinary retention drowsiness;
 dry mouth - tired feeling;
 diarrhea - dry mouth;
 constipation - sore throat,
Therapeutic Use: cough;
Allergic rhinitis - nausea,
Side effect/Adverse constipation; or
Reaction: - Headache
Combination  dizziness Contraindication:
antihistamine:  drowsiness glaucoma, an increased
 blurred vision pressure in the eye
AZELASTINE and  headache liver problems
FLUTICASONE  tachycardia decreased kidney
 palpitations function
 dysphonia an inability to
 dysgeusia completely empty the
 epistaxis bladder
AZELASTINE Mode of action:
primarily a selective
2ND GENERATION ANTIHISTAMINE antagonist of histamine
CETIRIZINE Mode of action: H1-receptors, with a
(ZYRTEC) - H1- lesser affinity for H2-
Antihistamine receptors, used for the
that does not symptomatic treatment
cross the BBB, of allergies.
and thus not Therapeutic Use:
produce such  allergic rhinitis
 conjunctivitis
114
 Side effect/Adverse Reaction:
Reaction:  drowsiness
 drowsiness,  dizziness
 headache  headache
 blurred vision  weakness
 dry mouth  dry mouth,
 weakness  nervousness
 Dysesthesia.  tachycardia
Mode of action: Mode of action:
considered an “inverse Like other H1-blockers,
agonist” of the H1 Desloratadine competes
receptor because it binds with free histamine for
to and stabilizes the binding at H1-receptors
inactive form of the in the GI tract, uterus,
receptor, preventing its large blood vessels, and
activation and bronchial smooth
FEXOFENADIN subsequent downstream muscle. This blocks the
E effects. action of endogenous
Therapeutic Use: histamine, which
 allergic rhinitis subsequently leads to
 chronic urticaria temporary relief of the
Side effect/Adverse negative symptoms (eg.
Reaction: nasal congestion, watery
 headache DESLORATADI eyes) brought on by
 nausea NE histamine.
 vomiting Therapeutic Use:
Mode of action:  allergic rhinitis
exerts it's effect by  chronic urticaria
targeting H1 histamine  pruritus
receptors. Side effect/Adverse
loratadine can more Reaction:
accurately be classified - Drowsiness
as an "inverse agonist" - Dizziness
as opposed to a - Headache
"histamine antagonist", - Irritability
LORATADINE and can prevent or - Weakness
reduce the severity of - Insomnia
histamine mediated - Nausea
symptoms. - Vomiting
Therapeutic Use: - Diarrhea
 allergic rhinitis
 pruritus EXPECTORANTS
 urticaria
Side effect/Adverse
115
• Loosen bronchial secretions so they can be Blood Pressure.
eliminated by coughing POTASSIUM Mode of action:
• A medication that helps bring up mucus IODIDE • It works by
and other material from the lungs, bronchi, shrinking the size of
and trachea. the thyroid gland
• Expectorants are ingredients that increase and decreasing the
airway secretions. amount of thyroid
• Hydration is the best natural expectorants hormones produced.
• Patient should increase fluid intake up to 8 • used to thin mucus
glasses per day to help lessen mucus. and loosen
GUAIFENESIN Mode of action: congestion in the
• is thought to act as chest and throat.
an expectorant by Side / adverse effect:
increasing the • Fever
volume and reducing • Tiredness.
the viscosity of • Nausea
secretions in the • Vomiting
trachea and bronchi. • Difficulty Breathing
• Promotes drainage (AE)
of mucus from the • Swelling of Neck
lungs by thinning and Throat (AE)
the mucus, and also • Chest Pain (AE)
lubricates the • Numbness (AE)
irritated respiratory Contraindications:
tract. • Active tuberculosis.
Side / adverse effect: • Goiter.
• Dizziness. • High levels of
• Drowsiness. potassium in the
• Nausea. blood.
• Vomiting. • Decreased kidney
• Headache. function.
• Difficulty Breathing • Pregnancy.
(AE) • Hashimoto
• Swelling of Face thyroiditis.
(AE) • Urticarial vasculitis.
Contraindications:
• Overactive Thyroid
Gland. SINUSITIS
• Diabetes. - an inflammation of the mucous membranes
• Closed Angle of one or more of the maxillary, frontal,
Glaucoma. ethmoid, or sphenoid sinuses. A systemic
• High Blood or nasal decongestant may be indicated.
Pressure.
• Significant ACUTE PHARYNGITIS
Uncontrolled High
116
- An inflammation of the throat or "sore such as albumin
throat," can be caused by a virus, beta- and secretory
hemolytic streptococci ("strep throat"), or IgA.
other bacteria. It can occur alone or with ➜ These drugs also
the common cold and rhinitis or acute act as
sinusitis. antioxidants and
MUCOLYTICS may therefore
Mode of action: reduce airway
➜ Mucolytics Mucolytics can inflammation
are medicines dissolve thick mucus
that make the and are usually used Doctors use NAC
mucus less thick to help relieve to treat
and sticky and respiratory acetaminophen
easier to cough difficulties. They do N- overdose. It may
up this by breaking ACETYLCYSTEIN also help break up
➜ This can help if down the chemical E mucus in people with
you have a bonds between some lung diseases,
condition that molecules in the like chronic
affects your mucus. This in turn bronchitis.
lungs, including: can lower the a type of medicine
chronic viscosity by altering called a mucolytic.
obstructive the mucin-containing A mucolytic helps
pulmonary components. you cough up
disease (COPD), CARBOCISTEINE phlegm (also called
cystic fibrosis Adverse effects and mucus or sputum). It
and other side effects- works by making
conditions  headache your phlegm less
including  nausea/vomiting thick and sticky. 
common colds  gastric a drug that aids the
marked by excess discomfort body's mucus-
mucus and a clearing processes in
 bleeding
productive cough BROMHEXINE the respiratory tract.
 diarrhea
➜ Several agents It is used to relieve
 rash chest congestion.
can reduce the
viscosity of Contraindications:
sputum in vitro.  should not be This medication is
One group used in children used to improve
consists of under 6 years old breathing and reduce
derivatives of  stomach ulcer the risk of lung
cysteine that PULMOZYME infections in
 acute
reduce the (DORNASE ALFA) people with cystic
bronchospasms
disulfide bridges fibrosis. Pulmozyme
 esophageal
that bind contains an enzyme
varices
glycoproteins to called a DNase that
other proteins, acts like molecular
117
 scissors to cut the Sympathetic nervous system
long DNA strands
into smaller pieces. ➜ Releases epinephrine, which stimulates the
This makes the beta2 receptor in the bronchial smooth
mucus thinner and muscle, resulting in bronchodilation.
easier to cough up. CYCLIC ADENOSINE
used for conditions MONOPHOSPHATE (cAMP)
where there are a lot
AMBROXOL
of thick mucus in the ➜ The cytoplasm of bronchial cells increases
airway passages bronchodilation by relaxing the bronchial
LOWER RESPIRATORY DISORDERS smooth muscles.
➜ Pulmonary enzyme phosphodiesterase can
CHEST CAVITY
inactivate cAMP.
➜ a closed compartment bounded by 12 ribs, RESTRICTIVE LUNG DISEASE
the diaphragm, thoracic vertebrae, sternum,
neck muscles, and intercostal muscles ➜ A decrease in total lung capacity as a result
between the ribs of fluid accumulation or loss of elasticity of
the lungs.
PLEURAE
CHRONIC OBSTRUCTIVE
➜ membranes that encase lungs PULMONARY DISEASE
LUNG COMPLIANCE
➜ Caused by airway obstruction with
➜ The lung volume based on the pressure in increased airway resistance of airflow to
the alveoli. This volume determines the lung tissue.
lung’s ability to stretch. ASTHMA
Factors that influence lung compliance:
➜ An inflammatory disorder of the airway
1. Connective tissue (collagen and elastin) walls associated with a varying amount of
2. Surface tension in the alveoli, which is airway obstruction.
controlled by surfactant ➜ Triggered by stimuli such as stress,
allergens, and pollutants
BRONCHIAL SMOOTH MUSCLE
➜ When activated by stimuli, the bronchial
Tracheobronchial tube airways become inflamed and edematous,
leading to constriction of air passages.
➜ Composed of smooth muscle whose fibers Inflammation aggravates airway
spiral round the tracheobronchial tube, hyperresponsiveness to stimuli, causing
becoming more closely spaced as they near bronchial cells to produce more mucus,
terminal bronchioles. Constriction of these which obstruct air passages.
muscles constricts airway.
Symptoms: wheezing, coughing, dyspnea
Vagus nerve (Parasympathetic nervous (breathless), chest tightness, bronchospasm
system) particularly at night or early in morning.
➜ Releases acetylcholine, which causes BRONCHIAL ASTHMA
bronchoconstriction
118
➜ One of the COPD lung disease, is ➜ A progressive lung disease caused by
characterized by period of bronchospasm cigarette smoking, atmospheric
(constricted bronchioles) resulting in contaminants, or lack of the alpha1 –
wheezing and difficulty breathing. antitrypsin protein that inhibits proteolytic
enzymes that destroy alveoli (air sacs).
Bronchospasm or bronchoconstriction, result
when lung tissue is exposed to extrinsic or Proteolytic enzymes, released in the lung by
intrinsic factors stimulate a bronchoconstrictive bacteria or phagocytic cells.
response.
SYMPATHOMIMETRICS: ALPHA- AND
Symptoms: same as asthma except wheezing. BETA2 – ADRENERGIC AGONIST
Factors that trigger asthmatic attack: Sympathomimetic drugs are known as
adrenergic agonists. These are stimulant
1. Humidity compounds which mimic the effects of
2. Air pressure changes endogenous agonists of the sympathetic
3. Temperature changes nervous system.
4. Smoke
5. Fumes (exhaust, perfume) It increases cAMP, causing dilation of the
6. Stress bronchioles. In an acute bronchospasm caused
7. Emotional upset by anaphylaxis, the nonselective
8. Exercise sympathomimetic epinephrine is given. Thus
9. Allergies to animal dander, dust mites, for bronchospasm associated with asthma or
foods , drugs COPD, selective beta2-adrenergic agonists are
given by aerosol or tablet.
Reactive airway disease (RAD)
ALBUTEROL
➜ Cause of asthma that results from
sensitivity stimulation from allergens, dust, ➜ A selective beta2 drug that is effective for
temperature changes, and cigarette treatment and control of asthma by causing
smoking. bronchodilation with a long duration of
action.
CHRONIC BRONCHITIS
METAPROTERENOL
➜ Progressive lung disease caused by
smoking or chronic lung infection. ➜ It works by relaxing muscles in the airways
➜ Bronchial inflammation and excessive to improve breathing. This can be
mucous secretion result in airway administered orally or by inhalation with a
obstruction. metered dose inhaler or a nebulizer. It is for
acute bronchospasm, asthma and COPD.
Hypercapnia (increased carbon dioxide ➜ Primarily used as beta2 agent
retention) and Hypoxemia (decreased blood
➜ Can be administered orally or by inhalation
oxygen) lead to respiratory acidosis.
with a metered-dose inhaler (MDI) or
Bronchiectasis, dilation of the bronchi and nebulizer.
bronchioles is abnormal secondary to frequent
infection and inflammation. USE OF AN AEROSOL INHALER

EMPHYSEMIA For long term asthma treatment, beta2

adrenergic agonists are frequently administered
119
by inhalation. It may be given by MDI or DPI. ● dizziness
Correct use of the inhaler and dosage intervals ● diaphoresis
need to be explained to the patient. ● weakness
● paresthesia
Drug inhalation may cause mouth dryness and
● hypo/
throat irritation. Excessive use can lead
hypergycemia
tolerance and loss of drug effectiveness.
● angina
Ocassionally, bronchoconstriction may also
● palpitations
develop. Frequent dosing may cause tremors,
● tachycardia
nervousness, and increased heart rate.
● hypertension
ADRRENERGIC BRONCHODILATOR ● dysrhymthia
Alpha- and beta- Therapeutic Use: REVEFENACIN Therapeutic Use:
adrenergics: ● It is admistered in ● long term
emergency maintenance
EPINEPRHINE situations to restore treatment of
SULFATE circulation and bronchospasm
Alpha1, beta1 , increase airway associated with
beta2 patency. COPD
● Asthma ● bronchitis
● Acute ● emphysema
bronchospasm Side effect:
● hypotension ● headache
Side effect: ● cough
● Tremors ● infection
● dizziness, ● pharyngitis
● hypertension, ● dizziness
● tachycardia, ● hypertension
● palpitations, ● back pain
● dysrhythmias, FORMOTEROL Therapeutic Use:
● angina ● asthma
● tremors ● bronchitis
● headache ● COPD
● increase blood ● emphysema
glucose levels ● prophylaxis of
EPINEPHRINE Therapeutic Use: exercise-induced
● acute bronchospasm
bronchospasm Side effect:
● asthma ● dizziness
● anaphylaxis ● insomnia
● angioedema ● tachycardia
● nasal congestion ● chest pain
● status asthmaticus ● palpitations
Side effect: ● hypokalemia
● restlessness ● infection
● tremors ● nausea
120
 ● diarrhea ● nasal congestion
● hyperglycemia ● palpitations
LEVALBUTERO Therapeutic Use: ● tachycardia
L ● asthma ● hypokalemia
● bronchospasm ● hyperglycemia
● prophylaxis ● arthralgia
Side effect: ● myalgia
● dizziness TERBUTALINE Therapeutic Use:
● nasopharyngitis SULFATE ● asthma
● nausea / vomiting ● COPD
● diarrhea ● bronchospasm
● headache prophylaxis
● chest pain Side effect:
● hyperglycemia ● dizziness
● hypokalemia ● drowsiness
● tachycardia ● headache
● fever ● chest pain
● candidiasis ● dyspnea
● tremors ● tremors
METAPROTERE Therapeutic Use: ● nausea
NOL SULFATE ● acute ● vomiting
bronchospasm ● palpitations
● asthma ● tachycardia
● COPD ● hypokalemia
Side effect: ARFORMOTER Therapeutic Use:
● headache OL TARTRATE ● COPD
● dizziness Side effect:
● nervousness ● restlessness
● nausea ● tremor
● diarrhea ● headache
● fatigue ● sinusitis
● blurred vision ● muscle cramps
● chest pain ● dyspnea
● hypokalemia ● peripheral edema
● tremor ● back pain
● tachycardia ● hyperglycemia
● palpitations ● chest pain
Therapeutic Use: ● tachycardia
● asthma ● diarrhea
● COPD INDACATEROL Therapeutic Use:
● bronchospasm ● COPD
prophylaxis Side effect:
Side effect: ● Cough
● headache ● headache
● pharyngitis ● nasopharyngitis
121
 ● hyperglycemia  - useful for treating respiratory disorders
● hypokalemia (asthma,COPD), Parkinson’s, cardiovascular
● hypertension disease, urinanry incontinence, psychiatric
● tachycardia disorders, depression, mydriasis, and allergies.
OLODATEROL Therapeutic Use:
ADVERSE EFFECTS
● COPD
Side effect:   - Central effects result from the excess
● cough blockade of cholinergic receptors within the
● nasopharyngitis central nervous system, and peripheral
● hypokalemia adverse effects result from the blockade of
● hyperglycemia exocrine glandular secretion, muscle
● constipation contraction, and end-organ targets of the
● infection peripheral parasympathetic nervous system. 
CONTRAINDICATIONS
ANTICHOLINERGICS
  - myasthenia gravis, hyperthyroidism,
Drugs that block the action of acetylcholine. glaucoma, enlarged prostate, hypertension
Most anticholinergic drugs interact with the (high blood pressure), urinary tract blockage,
muscarinic receptors in the brain, secretory increased, heart rate (tachycardia), heart
glands, heart, and smooth muscle. failure, severe dry mouth, hiatal hernia, severe
constipation, liver disease, and Down
MECHANISM OF ACTION
syndrome. 
  - Competitively inhibit binding of the
TIOTROPIUM Therapeutic effects:
neurotransmitter, acetylcholine. They target
- For maintenance
either muscarinic acetylcholine receptors or,
treatment of asthma
less commonly, nicotinic acetylcholine
and COPD
receptors. 
SIDE EFFECT: Mechanism of
action:
• dry mouth - Blocks muscarinic
• blurry vision cholinergic receptors
• constipation and antagonizes
• drowsiness acetylcholine action
• sedation by inhibiting M3
• hallucinations receptors response to
• memory problems acetylcholine.
• trouble urinating Thereby. Relaxing
• confusion smooth muscle of
• delirium bronchi; dilates
• decreased sweating bronchi
• decreased saliva
Side effect:
INDICATIONS  insomnia
 dizziness
122
  depression  Blurred vision
 headache  Tachycardia
 sinusitis  Palpitations
 nasopharyngitis  Epistaxis
 cough  Nasopharyngitis
 dry mouth  Dyspnea
 nausea  Urinary retention
 vomiting  constipation
 abdominal pain ACLIDINIUM Therapeutics uses:
 constipation COPD
 urinary retention bronchospasm
 arthralgia Side effect:
 myalgia  headache
 peripheral edema  blurred vision
 blurred vision  ocular
 oral ulceration hypertension
 infection  urinary retention
 anaphylaxis (AR)  Nasopharyngitis
 angioedema (AR) UMECLIDINIUM Therapeutics uses:
 dehydration (AR) COPD
Side effect:
 hyperglycemia
(AR)  Nasopharyngitis
 chest pain (AR)  Blurred vision
 GI obstruction  Ocular
(AR) hypertension
 Cataracts (AR)  Depression
 Tachycardia
Contraindications:  Urinary retention
- Hypersensitivity  Constipation
to atropine or its  infection
derivatives,
including
ipratropium, MONOCLONAL ANTIBODY
tiotropium, or their OMALIZUMAB Therapeutics uses:
components Asthma
IPRATROPIUM Therapeutics uses: Chronic urticaria
BROMIDE Side effect:
 Allergic rhinitis
 dizziness
 Common cold
 headache
 COPD
 pharyngitis
 Bronchospasm
prophylaxis  sinusitis
Side effect:  arthralgia
 Headache  bone fractures
 rash
123
  peripheral edema UM and  infection
 hypotension VILANTEROL  hypokalemia
 injection site GLYCOPYRR  palpitations
reaction OLATE and  chest pain
 infection FORMOTERO  tachycardia
RESLIZUMAB Therapeutics uses: L  edema /
asthma ACLIDINIUM Peripheral
Side effect: and edema
 pharyngitis FORMOTERO  urinary
 musculoskeletal L FUMARATE retention
pain  insomnia
 dyspnea  constipation
 antibody
formation
 hypotension METHYLXANTHINE (XANTHINE)
DERIVATIVES
 malignancy
DUPLILUMAB Therapeutics uses: ● Second major group of bronchodilators
Moderate to severe used to treat asthma
asthma
Side effect: ● Xanthines stimulate the central nervous
 injection site system (CNS) and respiration, dilate
reaction coronary and pulmonary vessels, and cause
 ocular pruritus diuresis
 conjunctivitis
● Aminophylline, Theophylline, and Caffeine
 blepharitis
 keratitis AMINOPHYLLIN Mechanism of
 xerophthalmia E- action:
 antibody THEOPHYLLINE relaxes the smooth
formation muscles of the
bronchi, bronchioles,
and pulmonary blood
COMBINATION BETA-ADRENERGIC vessels by inhibiting
AND ANTICHOLINERGICS the enzyme
IPATROPIUM Thera Side effect: phosphodiesterase,
and peutic  headache resulting in an
ALBUTEROL use:  blurred vision increase in cAMP,
INDACATER  pharyngitis / which promotes
OL and Nasopharyngiti bronchodilation
GLYCOPYRR COP s Therapeutic effect:
OLATE D  ocular  prevent and treat
OLODATERO hypertension / wheezing,
L and Hypertension  shortness of
TIOTROPIUM  hyperglycemia breath
UMECLIDINI  chest
124
 tightness caused or any component of
by asthma its formulation 
 Chronic
bronchitis,
LEUKOTRIENE RECEPTOR
 Emphysema
ANTAGONIST AND SYNTHESIS
 other lung INHIBITORS
diseases. It
relaxes and opens Leukotriene (LT), chemical mediator that can
air passages in cause inflammatory changes in the lung.
the lungs, making
it easier to Cysteinyl leukotrienes, promote an increase in
breathe. eosinophil migration, mucous production and
Side / Adverse airway wall edema that results in
Effects: bronchoconstriction.
 anorexia LT receptor antagonists and LT synthesis
 nausea/vomiting inhibitors called Leukotriene modifiers, are
 gastric pain effective in reducing the inflammatory
caused by symptoms of asthma triggered by allergic and
increased gastric environmental stimuli.
acid secretion
 Not recommended for treatment of
 intestinal
acute asthmatic attacks rather they are
bleeding
used for exercise-induced asthma.
 nervousness
 dizziness Leukotriene Mode of action:
 headache receptor Acts as a leukotriene
 irritability antagonist: receptor antagonist,
 cardiac reducing inflammation
dysrhythmias ZAFIRLUKAST process and
 tachycardia decreasing
 palpitations bronchospasm.
 marked Therapeutic Use:
hypotension Asthma
 hyperreflexia Side effect:
 Seizures  Headache
 restlessness,  Depression
 insomnia  Chet pain
 Restlessness
Contraindication:  Hyperbilirubinemi
Theophylline is a
contraindicated if the  Peripheral
patient previously neuropathy
developed a  Nausea/vomiting
hypersensitivity  diarrhea
reaction to the drug MONTELUKAST Therapeutic Use:
125
  Allergic rhinitis ROFLUMILAST  Depression
 Asthma  Headache
 For exercise-  Nausea
induced  Diarrhea
bronchospasm  Weight loss
propylaxis  Back pain
Side Effect:
 Agitation
 Insomnia GLUCOCORTICOIDS (STEROIDS)
 Confusion ➜ Used to treat respiratory disorders,
 Depression particularly asthma.
 Influenza ➜ These drugs have an anti-inflammatory
 Palpitations action and are indicated if asthma is
 Angioedema (AR) unresponsive to bronchodilator therapy or if
 Bleeding seizures the patient has an asthmatic attack while on
(AR) maximum doses of theophylline or an
 Suicidal ideation adrenergic drug.
(AR)
 Anaphylaxis (AR) METHODS:
 Thrombocytopenia  MDI Inhalator
(AR) o Not helpful in treating severe
Leukotriene MOA: asthmatic attack because it can take
synthesis inhibitor: It decreases the 1 to 4 weeks for an inhaled steroid
inflammatory process to reach its full effect.
ZILEUTON and decreases o More effective for controlling
bronchospasm. symptoms of asthma that are beta2
Therapeutic Use: antagonist, particularly in the
Asthma reduction of bronchial
Side effect: hyperresponsiveness.
 Headache o Minimizes the risk of adrenal
 Chills suppression associated with oral
 Asthenia systemic glucocorticoid therapy.
 Fatigue  Tablet
 Myalgia  Intravenous
 Abdominal pain
 Dyspepsia Therapeutic Use:
 Nausea Allergic rhinitis
Intranasal Nasal polyps
 Constipation
spray: asthma
 Sinusitis
Side effect:
 infection
BECLOME  Nasopharyngitis
Phosphodiesterase- Therapeutic use:
THASONE  Candidiasis
4 inhibitor: COPD
Side effect:  Dysphonia
 Hoarseness
126
  Epistaxis Side effect:
 Ocular hypertension  Headache
Therapeutic Use:  Candidiasis
 Rhinitis  Pharyngitis
 asthma  Cough
Side effect:  Fatigue
 Headache  Sinusitis
 Weakness  Wheezing
BUDESONI
 Fatigue  Arthralgia
DE
 Dyspepsia  epistaxis
 Nausea Therapeutic Use:
 Diarrhea Allergic rhinitis
 Cough Side effect:
 Rhinitis TRIAMCIN  Ocular hypertension
 epistaxis OLONE  Rash
Therapeutic Use:  Euphoria
 Allergic rhinitis  Blurred vision
 asthma  Nasal irritation
Side effect: Aerosol Inhalation
FLUNISOLI  Nasal irritation BECLOME
DE  Dysgeusia THASONE
 Hoarseness FLUNISOLI
 Ocular hypertension DE
 Dysphoria BEDUSONI
 candidiasis DE
Therapeutic Use: FLUTICAS
Allergic rhinitis ONE
Side effect: Oral and intravenous administration
 Headache CORTISON
Therapeutic Use:
E
 Blurred vision Adrenocortical insufficiency
ACETATE
 Fatigue
DEXAMET Therapeutic Use:
FLUTICAS  Insomnia HASONE Adrenocortical insufficiency
ONE  Arthralgia FLUDROC Therapeutic Use:
 Epistaxis ORTISONE Adrenocortical insufficiency
 Pharyngitis ACETATE (Addison disease)
 Nasal HYDROCO Therapeutic Use:
candidiasis/irritation RTISONE Adrenocortical insufficiency
 Dysphonia METHYLP
 Nausea/vomiting Therapeutic Use:
REDNISOL
Therapeutic Use: Adrenocortical insufficiency
MOMETAS ONE
 Allergic rhinitis Therapeutic Use:
ONE PREDNISO
 Nasal congestion Parenteral use in primary or
FUROATE LONE
polyps secondary adrenocortical
127
 insufficiency histamine and other inflammatory
Therapeutic Use: mediators from mast cells to prevent an
PREDNISO asthma attack
Adrenocortical insufficiency,
NE
Addison disease
Therapeutic Use:
Combination glucocorticoids and beta2
agonist  Allergic rhinitis
 Conjunctivitis
 Headache
 Asthma
 Blurred
vision  Exercise-
induced
 Pharyngitis
bronchospasm
 Tachycardia
prophylaxis
 Palpitate CROMOLYN Side effect:
FLUTICAS  Infection SODIUM  Headache
ONE and  oral  Cough
SALMETE candidiasis
 Hoarseness
ROL  nausea/
 Nausea
vomiting
 Diarrhea
 hyperglycemi
Therape  Palpitations
a
utic Use:  hypokalemia  Tachycardia
 Myalgia
 musculoskele
Asthma
tal pain
COPD
 headache GASTROINTESTINAL SYSTEM
 Nasopharyng
EMETICS
itis
FLUTICAS  candidiasis ➜ Drugs are used to induce vomiting.
ONE  fatigue ➜ When an individual has emetics are
FUROATE  infection indicated to expel the substance before
and  hyperglycemi absorption occurs. Vomiting can be
VILANTER a induced in a number of ways without using
OL  hypokalemia drugs, such as putting a finger in the back
 palpitations of the throat.
 tachycardia ➜ Vomiting should not be induced if caustic
 insomnia substances such as ammonia, chlorine
bleach, lye, toilet cleaners, or battery acid
have been the esophagus.
CROMOLYN
➜ To prevent aspiration, vomiting should
➜ Used for prophylactic treatment of ingested.
bronchial asthma, and it must be taken ➜ Regurgitating these substances can cause
daily. additional injury to also be avoided if
➜ Not used for acute asthmatic attacks petroleum distillates are ingested; these
➜ Does not have bronchodilator properties but include gasoline, kerosene, paint thinners,
instead acts by inhibiting release of and lighter fluid.
128
➜ Activated charcoal is given or gastric  Used to treat nausea and
lavage is done when emesis is vomiting resulting from
contraindicated surgery, anesthetics,
chemotherapy, and radiation
ANTIEMETICS (antivomiting agents) sickness.
 They act by inhibiting CTZ
➜ Vomiting (emesis), the expulsion of gastric
o Butyrophenones
contents, has a multitude of causes,
including motion sickness, viral and  Block the D2 receptors in the
bacterial infection, food intolerance, CTZ.
surgery, pregnancy, pain, shock, effects of  They are used to treat
selected drugs, radiation, and disturbances postoperative nausea and
of the middle ear that affect equilibrium. vomiting and emesis
associated with toxins,
➜ Antiemetics can mask the underlying cause
cancer chemotherapy, and
of vomiting and should not be used until
radiation therapy.
the cause dehydration and electrolyte
o Benzodiazepines
imbalance.
 Indirectly control nausea and
TWO MAJOR CEREBRAL CENTERS vomiting that may occur
with cancer chemotherapy.
Chemoreceptor trigger zone (CTZ), lies near o Serotonin- receptor antagonists
medulla  Suppress nausea and
Vomiting center, caused vomiting when vomiting by blocking the
stimulated. serotonin (5-HT3) receptors
in the CTZ and blocking the
TWO MAJOR GROUP OF afferent vagal nerve
ANTIEMETICS terminals in the upper GI
 Non prescription tract
o Can be purchased as over-the- o Glucocorticoids (corticosteroids)
counter (OTC) drugs.  Dexamethasone and
o Frequently used to prevent motion methylprednisolone are two
agents that are effective in
sickness but have minimal effect on
suppressing emesis
controlling severe vomiting
associated with cancer
resulting from anticancer agents,
chemotherapy.
radiation and toxins.
o Cannabinoids
 Prescription
 The active ingredients in
o Antihistamines and
Cannabis, were approved
anticholinergics
for clinical use in 1985 to
o Dopamine antagonist
alleviate nausea and
 These agents suppress vomiting resulting from
emesis by blocking cancer treatment.
dopamine (D2) receptors in  These agents may be
the CTZ. prescribed for patients
o Phenothiazine antiemetics receiving chemotherapy who
do not respond to or are
129
 unable to take other vomiting
antiemetics. Side effect:
o Miscellaneous antiemetics  Drowsiness
 Trimethobenzamide, in the  Dizziness
class of miscellaneous  Headache
antiemetics because it does  Restlessness
not act strictly as an  Blurred vision
antihistamines,  Anorexia
anticholinergics, or  Dry mouth
phenothiazine.
 Insomnia
 The drug suppresses
 tachycardia
impulses to the CTZ
MECLIZINE Therapeutic use:
 Metoclopramide,
HYDROCHLORI For prevention and
suppresses emesis by
DE treatment of nausea,
blocking the dopamine
vomiting, and
receptors in the CTZ.
dizziness due to
 Used in the treatment
motion sickness and
of postoperative
vertigo associated
emesis, cancer
with vestibular
chemotherapy, and
disorder.
radiation therapy
Side effect:
NONPRESCRIPTION ANTIEMETICS:  Drowsiness
antihistamines  headache
Motion sickness: Therapeutic use:  ataxia
CYCLIZINE  Prevention and  fatigue
HYDROCHLORI treatment of  blurred vision
DE nausea, vomiting  dry mouth
and dizziness PRESCRIPTION ANTIEMETICS
associated with Antihistamines: Therapeutic use:
motion sickness  Postoperative
 Avoid concurrent HYDROXYZINE nausea and
alcohol use vomiting
Side effect:  Vertigo
 Drowsiness  Anxiety
 Blurred vision  Agitation
 Fatigue  Sedation
 Xerostomia induction
 Anorexia  Give deep in large
 Constipation muscle
 Nasal dryness Side effect:
DIMENHYDRINA Therapeutic use:  Drowsiness
TE Prevent and treat  Dizziness
motion sickness,  Fatigue
dizziness, nausea and
130
  Ataxia  nausea/vomiting,
 Headache  sedation induction
 Blurred vision Side effect:
 Dry mouth  confusion
 Urinary retention  agitation
 constipation  anorexia
Anticholinergics: Therapeutic use:  dry mouth
Nausea/vomiting  constipation
SCOPOLAMINE Motion sickness  blurred vision
(Transdermal patch) IBS  excitability
Side effect:  photosensitivity
➜ alternative ears  Dizziness  fatigue
if using for  Drowsiness  hypo/hypertension
longer than 3d,  Headache  urinary retention
wash hands after  Fatigue
 injection site
applying patch,  Blurred vision reaction
and wear no  Restlessness  incoordination
more than one
 Orthostatic  slate gray skin
patch at a time
hypotension hyperpigmentatio
 Dry mouth n
 constipation  erectile/
Dopamine Therapeutic use: ejaculation
antagonist  Nausea / vomiting dysfunction
Phenothiazine:  Schizophrenia  extrapyramidal
 anxiety syndrome (AR)
PROCHLORPER Side effect:  seizures (AR)
AZINE  Drowsiness  NMS (AR)
MALEATE  Dizziness  Agranulocytosis
 Headache (AR)
Not approved for
 Insomnia CHLORPROMAZ Therapeutic use:
patients with
 Blurred vision INE  Nausea/vomiting
dementia-related
psychosis  Tachycardia  Hiccups
 Hypotension  schizophrenia
 EPS Side effect:
 Erectile/  Drowsiness
ejaculatory  Dizziness
dysfunction  Weight gain
 Constipation  Xerostomia
 Urinary retention  Photosensitivity
PROMETHAZINE Therapeutic use:  Akathisia
 To treat and  Dystonic reaction
prevent motion  pseudoparkinsonis
sickness, m
131
Butyrophenones: Therapeutic use:  headache
 Postoperative  weakness
DROPERIDOL nausea/vomiting  hematoma
 Sedation  fatigue
induction  anorexia
Side effect:  abdominal pain
 Hypo/  diarrhea
hypertension  constipation
 Tachycardia  injection site
 Dizziness reaction
 Drowsiness ONDANSETRON Therapeutic use:
 Anxiety HYDROCHLORI Postoperative and
 Restlessness DE chemo-induced
 Dysrhythmias nausea/vomiting
 EPS Side effect:
Benzodiazepines: Therapeutic use:  dizziness
 For prevention of  drowsiness
LORAZEPAM chemo-induced  agitation
nausea/vomiting  headache
 Anxiety  fatigue
 Insomnia  diarrhea
 Procedural  hypotension
sedation  urinary retention
 Status epilepticus  fever
Side effect:  constipation
 Dizziness PALONOSETRO Therapeutic use:
 Drowsiness N Postoperative and
 Ataxia chemo-induced
 Confusion nausea/vomiting
 Injection site Side effect:
reaction  Headache
 EPS  Dizziness
 Constipation  Hypotension
 Weakness  Flatulence
 Hypotension  Constipation
 Restlessness  Diarrhea
 dependence  Urinary retention
Serotonin (5-ht3) Therapeutic use: DOLASETRON Therapeutic use:
receptor Radiation- and Nausea/vomiting
antagonists: chemo-induced Side effect:
nausea and vomiting  Headache
GRANISETRON Side effect:  Dizziness
 dizziness  Confusion
132
  Edema anesthetics Seizures
 Hypotension EPS
 Palpitations diarrhea
 Constipation APREPITANT Therapeutic use:
Cannabinoids: Therapeutic use: Postoperative and
 Anorexia chemo-induced
DRONABINOL  Chemo-induced nausea and vomiting
CSS III nausea/vomiting Side effect:
Side effect: Dizziness
Fatigue
 Dizziness
Headache
 Drowsiness
Weakness
 Impaired Hypotension
cognition Hiccups
 Euphoria Cough
 Dysphoria Abdominal pain
 Paranoia Dyspepsia
 Ataxia Diarrhea
 Tachycardia constipation
 Hypotension NETUPITANT Therapeutic use:
 Nausea/vomiting and Postoperative and
 Abdominal pain PALONOSETRO chemo-induced
Miscellaneous: Therapeutic use: N nausea and vomiting
Postoperative and Side effect:
METOCLOPRAM chemo-induced Headache
IDE nausea and vomiting Asthenia
HYDROCHLORI Diabetic gastroparesis Fatigue
DE GERD Dyspepsia
Side effect: Urinary retention
Avoid alcohol and Drowsiness constipation
CNS depressants Visual disturbances ROLAPITANT Therapeutic use:
Fatigue Chemo-induced
Restlessness nausea and vomiting
Headache Side effect:
Nausea/vomiting Dizziness
TRIMETHOBENZ Therapeutic use: Anorexia
AMIDE Nausea/vomiting Abdominal pain
HYDROCHLORI Side effect: Dyspepsia
DE Drowsiness Infusion site reaction
Dizziness Hiccups
Avoid CNS Headache Stomatitis
depressants and if Hypotension infections
sensitive to Blurred vision
benzocaine or Muscle cramps
similar local DIARRHEA
Injection site reaction
133
Diarrhea, frequent liquid stool, is a symptom of ➜ Nonpharmacologic treatment for diarrhea is
an intestinal disorder. recommended until the underlying cause
Causes include: can be determined.
➜ This includes use of clear liquids and oral
1. Foods (spicy, spoiled) solutions such as Gatorade (for adults) and
2. Fecal impaction Pedialyte or Rehydralyte (for children) and
IV electrolyte solutions.
3. Bacteria (Escherichia coli, Salmonella) or ➜ Antidiarrheal drugs are frequently used in
viruses (parvovirus, rotavirus) combination with nonpharmacologic
4. Toxins treatment.

5. Drug reactions Travelers’ Diarrhea

6. Laxative abuse Travelers' diarrhea, also called acute diarrhea,

is usually caused by E. coli, it ordinarily lasts
7. Malabsorption syndrome caused by lack of less than 2 days; however, If it becomes severe,
digestive enzymes fluoroquinolone antibiotics are usually
prescribed. Loperamide may be used to slow
8. Stress and anxiety peristalsis and decrease the frequency of
9. Bowel tumor defecation, but it can also slow the exit the
organism from the Gl tract. Travelers diarrhea
10. Inflammatory bowel disease such as can be reduced by drinking bottled water,
ulcerative colitis or Crohn disease, Diarrhea washing fruit, and eating cooked vegetables.
can be mild to severe. Meats should be cooked until well done.
➜ Antidiarrheals should not be used for more ANTIDIARRHEALS
than 2 days and should not be used if fever
is present. There are various antidiarrheals for treating
diarrhea and decreasing hypermotility
➜ Because intestinal fluids rich in water,
(increased peristalsis). Usually, an underlying
sodium, potassium, and bicarbonate,
cause of the diarrhea needs to be corrected as
diarrhea can cause minor or severe
well.
dehydration and electrolyte imbalances.
The loss of bicarbonate places the patient at The antidiarrheals are classified as
risk for developing metabolic acidosis.
Patients with diarrhea should avoid milk 1. Opiates and opiate -related agents
products and foods rich in fat. 2. Adsorbents
➜ Diarrhea can develop very quickly and can
be life threatening to young patients and 3. Miscellaneous antidiarrheals.
older adults, who may not be able to OPIATES AND OPIATE-RELATED
compensate for the fluid and electrolyte AGENTS
losses.
➜ Opiates decrease intestinal motility, thereby
NONPHARMACOLOGIC MEASURES decreasing peristalsis. Constipation is a
➜ The cause of diarrhea should be identified. common side effect of opium preparations,
Codeine is an example.

134
➜ Opiates are frequently combined with other 1. Fecal impaction
antidiarrheal agents. Opium antidiarrheals 2. Bowel obstruction
can cause CNS depression when taken with
alcohol, sedatives, or tranquilizers. 3. Chronic laxative use
➜ The duration of action of opiates is
4. Neurological disorders plegia
approximately 2 hours.
5. Ignoring the urge to defecate
ADSORBENTS
6. Lack of exercise
Adsorbents act by coating the wall of the Gl
tract and adsorbing includes these other 7. Select drugs such as anticholinergics,
antidiarrheals. Adsorbent antidiarrheals include narcotics, and certain antacids.
kaolin and pectin. These agents are combined
as a mild or moderate antidiarrheal that can be Osmotic (Saline) Laxatives
purchased without a prescription and used in Osmotics, hyperosmolar laxatives, include salts
combination with other antidiarrheals. Bismuth or saline products, lactulose, and glycerine.
subsalicylate is considered an adsorbent Saline products consist of sodium or
because it adsorbs bacterial toxins. Bismuth magnesium, and a small amount is systemically
subsalicylate is an OTC drug commonly used absorbed. Serum electrolytes should be
to treat travelers' diarrhea, and can also be used monitored to avoid electrolyte imbalance,
as an antacid for gastric discomfort. Side Hyperosmolar salts pull water into the colon
effects include dizziness, drowsiness, and increase water in the feces to increase bulk
weakness, headache, tongue and stool which stimulates peristalsis. Saline cathartics
discoloration. and anxiety. Colestipal and cause a semiformed to watery stool according
cholestyramine are prescription drugs that have to low or high doses. Good renal function is
been used to treat diarrhea due to excess bile needed to excrete any excess salts. Saline
acids in the colon. They are effective, although cathartics are contraindicated for patients with
they have not been approved by the FDA for heart failure.
this purpose.
STIMULANT (CONTACT) LAXATIVES
Miscellaneous Antidiarrheals
Stimulant (contact or irritant) laxatives increase
Various miscellaneous antidiarrheals are peristalsis by irritating sensory nerve endings
prescribed to control diarrhea. This group in the intestinal mucosa. Types include those
includes rifaximin. Side effects include that contain bisacodyl, senna, and castor oil
dizziness, nausea. dry mouth, flatulence, (purgative). Bisacodyl is the most frequently
constipation, and fatigue. used and abused laxative and can be purchased
CONSTIPATION OTC. Bisacodyl and several others of these
drugs are used to empty the stool, cathartics
Constipation, the accumulation of hard fecal result in a soft to watery stool with tone
material in the large intestine, is a relatively laxatives Bisacodyl lists the pharmacological
common complaint and major problem for data for the stimulant laxative bowel before
older adults. Insufficient water intake and poor diagnostic tests (barium enema).
dietary habits are contributing factors.
Castor oil is a harsh laxative (purgative) that
Other causes include: acts on the small bowel and produces a watery
stool. The action is quick, within 2 to 6 hours,
135
so the laxative should not be taken at bedtime.
Castor oil is not FDA approved to correct
constipation, rather it is used mainly for bowel
preparation. LAXATIVES
BULK-FORMING LAXATIVE Osmotic: Saline Therapeutic Use:
constipation
➜ Natural fibrous substances that promote GLYCERIN Side effect:
large, soft stools by absorbing water into Perianal irritation
the intestine, increasing fecal bulk and LACTULOSE Therapeutic Use:
peristalsis. Constipation
➜ These agents are nonabsorbable. Hepatic
➜ Defecation usually occurs within 8 to 24 encephalopathy
hours; however, it may take up 3 days after Side effect:
drug therapy is started for the stool to be Flatulence
soft and well formed. Eructation
Metabolic acidosis
➜ Powdered bulk-forming laxatives, which is
Hypokalemia
sometimes come in flavoured and sugar-
hypernatremia
free forms, should be mixed in a glass of
MAGNESIUM Therapeutic Use:
water or juice, stirred, drunk immediately,
CITRATE Constipation
and followed by a half to a full glass of
Bowel preparation
water.
Side effect:
➜ Insufficient fluid intake can cause the drug Abdominal cramps
to solidify in the GI tract, which can result Flatulence
in intestinal obstruction. Hypermagnesemia
➜ Does not cause laxative dependence and Dehydration
may be used by patients with diverticulosis, MAGNESIUM Therapeutic Use:
irritable bowel syndrome (IBS), and HYDROXIDE Constipation
ileostomy and colostomy. Dyspepsia
CHLORIDE CHANNEL ACTIVATORS Pyrosis
Side effect:
➜ Used to treat idiopathic constipation in Chalky taste
adult Dehydration
Hypermagnesemia
EMOLLIENTS (stool softeners) Stimulants: Therapeutic Use:
➜ Lubricants and stool softeners used to Bowel preparation
prevent constipation BISACODYL Constipation
Side effect:
➜ Decrease straining during defecation
Rectal burning
➜ Work by lowering surface tension and Hypokalemia
promoting water accumulation in the Dependence
intestine and stool CASTOR OIL Therapeutic Use:
➜ Prescribed to patient with myocardial Bowel preparation
infarction or surgery Side effect:
Steatorrhea
136
 Pruritus ani XONE Opioid induced
SENNA Therapeutic Use: constipation
Constipation Side effect:
Bowel preparation Abdominal
Side effect: pain/distension
Fluid and Flatulence
electrolytes hyperhidrosis
imbalances PRUCALOPRIDE Therapeutic Use:
Diarrhea Chronic idiopathic
Abdominal cramps constipation
Selective Chloride Therapeutic Use: Side effect:
Channel Activator: Constipation Diarrhea
IBS Flatulence
LUBIPROSTONE Opioid- induced Abdominal pain
constipation TENAPANOR Therapeutic Use:
Side effect: IBS with
Peripheral edema constipation
Fatigue Side effect:
Hypotension Flatulence
Flatulence Diarrhea
Miscellaneous: Therapeutic Use: GI bleeding
Constipation Bulk forming: Therapeutic Use:
LINACLOTIDE IBS Constipation
Side effect: POLYCARBOPHI IBS
Flatulence L Side effect:
Abdominal Anorexia
distension/pain Flatulence
Hypokalemia Abdominal cramps
Hyponatremia Distension
Infection POLYETHELYEN Therapeutic Use:
hypotension E GLYCOL Constipation
NALOXEGOL Therapeutic Use: Bowel preparation
Opiate agonist- Side effect:
induced constipation fecal incontinence
Side effect: abdominal cramps
Flatulence flatulence
Hyperhidrosis METHYLCELLUL Therapeutic Use:
NALDEMEDINE Therapeutic Use: OSE Constipation
Opiate agonist- Side effect:
induced constipation GI obstruction
Side effect: Abdominal cramps
Abdominal pain Diarrhea
Nausea/vomiting PSYLLIUM Therapeutic Use:
Diarrhea HYDROPHILIC Constipation
METHYLNALTRE Therapeutic Use: MUCILLOID Side effect:
137
 Esophageal or
intestinal obstruction
Flatulence
Anorexia
Diarrhea
Emollients: Stool Therapeutic Use:
Softeners Constipation
Side effect:
DOCUSATE Throat irritation
CALCIUM; Diarrhea
DOCUSATE Abdominal pain
SODIUM
DOCUSATE Therapeutic Use:
SODIUM WITH constipation
SENNA Side effect:
Hypocalcemia
Hypokalemia
Flatulence
Abdominal cramps
Emollient: Therapeutic Use:
Lubricant Constipation
Fecal impaction
MINERAL OIL Cardiac disorder
Anorectal surgery
Side effect:
fecal
urgency/incontinence
skin irritation
anal leakage
Evacuant / Bowel Therapeutic Use:
Preparation: Constipation
Bowel preparation
POLYETHYLENE Side effect:
GLYCOL- Flatulence
ELECTROLYTE Abdominal cramps
Fecal
urgency/incontinence

138