PITUITARY

Drugs/
MOA & Pharmacokinetics Pharmacodynamics Adverse Effects
Drug Group
GROWTH HORMONE AGONIST
Somatropin [B] MOA Indications ● Peripheral edema
● Binds to JAK/STAT cytokine ● Growth hormone deficiency ● Myalgia, arthralgia (because it
receptor ● Short stature makes your muscles and bones
● (+) Insulin-like Growth Factor 1 ○ Turner, Noonan, Prader-Willi grow)📣
(IGF-1)/ somatomedin C ● Failure to thrive due to chronic renal failure in ● Intracranial hypertension
PK SGA (Small for Gestational Age) patients ● Pseudotumor cerebri
● Injected 0.05-0.1 mg subcutaneously ● AIDS wasting ● Slipped capital femoral
every 8-12 hours, 6-7 times per ● Improve GI function in patients who epiphysis- ball at the head of the
week underwent intestinal resection that led to femur slips off the neck of the bone
● T1/2: 20 min; peak: 2-4 hours; malabsorption syndrome in a backwards direction
duration 36 hours ● Progression of scoliosis
● Hepatic clearance ● Hyperglycemia
Mecasermin [C] IGF-1 recombinant Indications ● Hypoglycemia
Stimulates skeletal muscle growth, ● For children unresponsive to GH therapy ○ Remedy give patient some
amino acid transport, protein snacks prior to dose
synthesis, and cell proliferation ● Increased liver function tests (LFT)
● Intracranial hypertension
GROWTH HORMONE ANTAGONIST
Pegvisomant [C] GH receptor antagonist Indications ● Diarrhea
PK ● Acromegaly ● Nausea
● Onset of action expected within 2 ● Flu-like syndrome
weeks of use ● Elevated liver function tests
● Hypersensitivity reaction
Octreotide [B] MOA Indications ● GI disturbances
Lanreotide ● Suppresses the release of growth ● Acromegaly ● Gallstones
hormones, glucagon, insulin, ● Pituitary adenomas (GH-secreting) ● Arrhythmias/cardiac conduction
For cancer gastrin, IGF-1, serotonin, and ● Carcinoid abnormality
gastrointestinal peptides ● Gastrinoma
● Glucagonoma
● Variceal bleeding
Dosage
● Regular release: given BID - QID SC
● If slow release: every 4 weeks, IM
● Long-acting synthetic analog of somatostatin
FOLLICLE-STIMULATING HORMONE AGONIST
Follitropin alfa [X] MOA Indications ● Headache
Menotropins ● Activates FSH receptors, mimics ● Controlled ovarian hyperstimulation ● Depression
Urofollitropin effects of endogenous FSH ● hypogonadotropic hypogonadism ● Edema
Follitropin Beta ● Follicle development (female) ● Multiple pregnancies in women
● Spermatogenesis (men) Men Female ● Gynecomastia in men
2o testicular failure Amenorrhea ● Ovarian hyperstimulation
Low libido Oligomenorrhea syndrome (ovarian enlargement,
Infertility (irregular mens) ascites, hypovolemia, shock)
Breast atrophy
Osteoporosis
LUTEINIZING HORMONE AGONIST
Choriogonadotropin MOA Indications ● Ovarian hyperstimulation
alfa [X] ● Gonadotropin analog ● Initiation of ovulation during controlled ● Headache
● Activates LH receptors, mimics ovarian hyperstimulation ● Depression
Menotropin (hMG) effects of endogenous LH ● Ovarian follicle development in women with ● Edema
Lutropin alfa hypogonadotropic hypogonadism
● Male hypogonadotropic hypogonadism

GnRH RECEPTOR AGONIST

Leuprolide [X] – MOA Indications ● Hot flushes
(longest acting) ● GnRH analog ● Ovarian suppression ● Osteoporosis
● Intermittent administration: ● Controlled ovarian hyperstimulation ● Gynecomastia
Gonadorelin increased LH and FSH secretion ● Endometriosis ● Reduced libido
(synthetic human GnRH) ● Prolonged and continuous ● Myoma uteri ● Decreased hematocrit
Goserelin administration: reduced LH and ● Central precocious puberty ● Temporary exacerbation of
Histrelin FSH secretion ● Advanced prostate cancer precocious puberty or prostate
Nafarelin cancer, apoplexy and blindness
Triptorelin during the first few weeks of
therapy (Remedy: co-administer
Flutamide, an androgen receptor
antagonist)
●
GnRH RECEPTOR ANTAGONIST
Ganirelix [X] MOA Indications ● Hot flushes
Cetrorelix ● GnRH antagonist ● Prevents premature LH surge during ● Osteoporosis
Abarelix ● Reduced endogenous production of controlled ovarian hyperstimulation ● Gynecomastia
Degarelix LH and FSH ● Advanced prostate cancer ● Reduced libido
● Decreased hematocrit
● Hypersensitivity (abarelix)
D2 DOPAMINE AGONIST
Bromocriptine [B] MOA Indications ● CI: patients with history of
● D2 dopamine agonist ● Hyperprolactinemia psychotic illness
● Inhibits prolactin release from the ● Pituitary adenoma ● Erythromelalgia
pituitary gland ● Acromegaly ● Raynaud’s phenomenon
● Slightly inhibits GH release ● Parkinson’s disease (vasospasm, skin turns purple)
● Dopaminergic effects on CNS motor ● Pulmonary infiltrates in high doses
control and behaviour ● Orthostatic hypotension
OXYTOCIN AGONIST
Oxytocin [X] MOA Indications ● CI: fetal distress, prematurity
● Activates oxytocin receptors ● Labor induction, labor augmentation ● Fetal distress
● Stimulates uterine contraction and ● Control of postpartum hemorrhage (uterine ● Placental abruption
labor atony) ● Uterine rupture
● Stimulates mammary glands, ● Fluid retention
lactation, and milk let-down ● Hyponatremia
● Heart failure
● Seizures
● Hypotension
Carbetocin Peripheral oxytocin receptor agonist ●
OXYTOCIN ANTAGONIST
Atosiban Oxytocin receptor blocker ● Increase infant death rate
VASOPRESSIN AGONIST
Desmopressin [B] MOA Indications ● GI disturbances
● ADH agonist ● Central diabetes insipidus ● Hyponatremia
● Relatively selective for V2 ● Hemophilia A ● Seizures
receptors increased factor VII and ● Von Willebrand’s disease ● Allergic reactions
VWF ● Esophageal variceal bleeding
● Decreased excretion of water ● Primary nocturnal enuresis (pedia px)
● Contracts vascular smooth muscle ● Colon diverticula
via V1 receptor  vasoconstriction
(tx for variceal bleeding and
diverticula)
VASOPRESSIN ANTAGONIST
Conivaptan [C] MOA Indications ● Infusion site reactions
● ADH antagonist ● SIADH ● Hyperkalemia
Tolvaptan ● Antagonist at V1a and V2 receptors ● Hyponatremia in hospitalized patients ● Central Pontine Myelinolysis
Lixivaptan ● Promotes renal excretion of water in ● Offset fluid retention in acute heart failure and may occur with rapid correction of
conditions associated with increased SIADH which causes hyponatremia hyponatremia
vasopressin
●
THYROID
 Drugs/
MOA & Pharmacokinetics Pharmacodynamics Adverse Effects
Drug Group
THIOAMIDE
Thioamide MOA Indications ● Contraindicated for pregnant
● commonly used in the Philippines ● Growth hormone deficiency women due to its ability to
● Short stature cross placental barrier and
○ Turner, Noonan, Prader-Willi cause fetal hypothyroidism and
● Failure to thrive due to chronic renal failure in its adverse effects
SGA (Small for Gestational Age) patients ●
● AIDS wasting
● Improve GI function in patients who
underwent intestinal resection that led to
malabsorption syndrome

Propylthiouracil MOA preferable during the first trimester of ● Maculopapular pruritic rash (4-
more strongly protein-bound  pregnancy 6%) - most common
crosses the placenta less readily ● Agranulocytosis: most
● prevent thyroid hormone dangerous complication
synthesis ● Nausea
○ inhibiting the thyroid peroxidase ● GI distress
catalyzed reactions ● Urticarial rash
○ blocking iodine organification , ● Vasculitis
coupling of iodoytyrosine ● Lymphadenopathy
● large first-pass effect in the liver ● Hypoprothrombinemia
● short plasma half-life of 1.5 hours ● Exfoliative dermatitis
● rapidly absorbed ● Polyserositis
● 50-100mg ● Acute arthralgia
Methimazole MOA 2nd-3rd trimester as PTU can cause fatal ● Severe hepatitis –
● 10x more potent than PTU hepatitis Propylthiouracil
● prevent hormone synthesis ● Severe hepatitis (black box
○ inhibiting the thyroid peroxidase warning)
catalyzed reactions METHIMAZOLE
○ blocking iodine organification , ● Cholestatic jaundice
coupling of iodoytyrosine ● Altered sense of taste and smell
● short plasma half-life of 6 hours -
● 65–70%: in urine in 48 hours ●
● 20-40mg OD/BID

ANION INHIBITOR
-
Perchlorate (ClO ) 4 ● Iodine-induced hyperthyroidism (eg. ● aplastic anemia
Pertechnetate amiodarone-induced hyperthyroidism)
(TcO4-) Block iodide uptake
Thiocyanate (SCN-)

IODIDES
e.g. Lugol’s solution ● Inhibit organification and hormone ● Thyroid storm (improvement within 2-7 ● induce hyperthyroidism (Jod-
Iodine release days) Basedow phenomenon)
Potassium iodide ● decrease the size and vascularity ● Preoperative preparation for surgery ● precipitate hypothyroidism
of the hyperplastic gland ● Initiated after onset of thioamide therapy ● prevent use of RAI (Radioactive
● Delay onset of thioamide therapy Iodine) treatment for several
weeks
● Fetal goiter
● Iodism [not common] 📣
(adverse reactions to iodine)
characterised by:
○ Acneiform rash
○ Swollen salivary glands
○ Mucous membrane
ulcerations
○ Conjunctivitis
○ Rhinorrhea
○ Drug fever
○ Metallic taste
○ Bleeding disorders
○ Anaphylactoid reactions

● RADIOACTIVE IODINE
131
Sodium Iodide ● Emits beta rays (400 to 2000μm)  Hyperthyroidism ● Contraindications:
Solution destruction of the thyroid Grave’s Disease ○ Pregnant women and nursing
thyrotoxicosis parenchyma Primary inoperable thyroid CA mothers
● Trapped within the thyroid gland Thyroxoxicosis ● crosses the placenta:
125
Sodium Iodide and enters the intracellular iodine destroys fetal thyroid gland and
Solution pool it is excreted in breast milk
diagnosis ● Delivers predominantly strong beta ○ Permanent hypothyroidism
radiation resulting in destruction ○ fetal hypothyroidism if given
of the follicular cells. in pregnancy
● Advantages ○ Potential for genetic damage
○ Easy administration ○ May precipitate thyroid crisis
○ Effectiveness ● Myxedema in adults
○ Low expense
○ Absence of pain
●
BETA BLOCKERS
Metoprolol No intrinsic sympathomimetic activity ● Therapeutic adjunct in thyrotoxicosis ●
Propranolol ● Does not lower thyroid levels ● Thyroid storm
Atenolol significantly ● Post-MI prophylaxis against sudden death
● Slow pacemaker activity ● Hypertension
● Membrane stabilizing action: ● thyrotoxicosis-related arrhythmias
Inhibits the peripheral ○ esmolol
conversion of T4 to T3
(Propranolol > 160 mg/day)

Drugs/
MOA & Pharmacokinetics Pharmacodynamics Adverse Effects
Drug Group
SYNTHETIC THYROID HORMONE
Synthetic MOA Indications
Levothyroxine ● synthetic version of one of the Drug of Choice for thyroid replacement and
body’s natural thyroid hormones: suppression therapy
thyroxine (T4) - Stable, Content uniformity
● Activation of nuclear receptors - Low cost, Lack of allergenic foreign
results in gene expression with protein, Easy laboratory
RNA formulation and protein measurement of serum levels
synthesis - Long half life (7 days)
■ Increase ATP hydrolysis T4 is converted to T3 intracellularly
■ Increase in oxygen
consumption contributing to MYXEDEMA COMA
thermogenesis - progressive weakness, stupor,
● hypothermia, hypoventilation,
hypoglycemia, hyponatremia, water
intoxication, shock, and death.
- Medical emergency
Leiothyronine MOA Cardiotoxic
3-4x more potent than levothyroxine ● avoided in patients with
cardiac disease due to
Not for routine replacement therapy: significant elevations in peak
● difficulty in monitoring levels and a greater risk of
● shorter half-life (24 hours cardiotoxicity

Liotrix MOA ● Disadvantage: expensive

● Thyroxine (T4) and liothyronine
(T3) fixed-dose combination
Desicated thyroid From dried and defatted animal Disadvantage
thyroid glands ● Protein antigenicity
Combination of T3, T4, MIT, and DIT ● Product instability
● Variable hormone concentration
●
Adrenoceptor ●
Blocking Agents
●
Thyrotoxicosis excessive thyroid hormone not Thyroid Storm ● Life-threatening syndrome-
necessarily from the thyroid gland sudden acute exacerbation of
○ Destruction in the thyroid gland all the symptoms of
causing release and elevation of thyrotoxicosis
stored T3 or T4 into the ● Granulocyte count: <500
circulation cells/mm³
 hormones ● Growth and differentiation
Inhibitors ○ Myelination
IODINE First step in thyroid Anion inhibitor ○ Cretinism - physical and mental
TRAPPING synthesis Large amount of retardation caused by lack of thyroid
150mcg daily iodide hormones during fetal development
e.g. iodized salt, fish, ○ Affects musculoskeletal,
seafood, drugs, water gastrointestinal, and reproductive
Sodium Iodide Iodide transporter to systems
● Temperature regulation
Symporter thyroid gland
– Hashimoto’s thyroiditis ● auto-immune disorder which attacks
the thyroid gland resulting to
Pendrin enzyme controlling the hypothyroidism
flow of iodide acors the Grave’s disease/Diffuse ● An autoimmune disorder where
membrane toxic goiter/Exophthalmic lymphocytes secrete a TSH receptor-
also in cochlea of inner goiter stimulating antibody(TSH-R Ab[stim])
ear  thyroid-stimulating
IODINE Oxidation of iodide by Thioamide: immunoglobulin(TSI)
ORGANIFICATI thyroidal peroidase  propylthiouracil ● Increased T3/T4 , Decreased TSH
ON iodine Methimidazole
In thyroglobulin
Drug MOA
molecue: iodination of
tyrosin residues  MIT Propylthiouracil Block thyroid hormone synthesis
and DIT Potassium iodide Retards release of thyroid hormone
EXOCYTOSIS T4, T3, DIT MIT release Iodides
PROTEOLYSIS  thyroglobulin Propranolol* Control severe cardiovascular manifestations
(hypertension and tachycardia)
PERIPHERAL T3: higher at periphery
METABOLISM Thyroxine deiodination Hydrocortisone Protects against shock;
of 5’ deiodinase enzyme Radiocontrast Block the conversion of T4 to T3
Monoiodination of T4  media Diltiazem If β blockers* are contraindicated by the presence of
3,5,3’ triiodothyronine Beta blockers severe heart failure or asthma(Katzung, 14th ed., p.699)
Cortitosteroids
D1 24% circulating T3 amiodarone
HYPERTHYROIDISM HYPOTHYROIDISM
D2 65% of periphertal T3
Regulates T3 levels in Warm, moist skin Pale, cool, puffy skin
brain and pituitary Heat intolerance (sweating) Cold sensation
Polymorphism
Tachycardia; increased SV, CO Bradycardia; decreased SV, CO
D3 Inactivates T3
Variable T4 T3 Menstrual irregularity Infertility; impotence

Volume of distribution 10L 40L Increased appetite Decreased appetite

Extrathyroidal pool 800mcg 54mcg Tremor, nervousness Lethargy; slowing of mental

processes
Daily production 75mcg 25mcg
Weight loss Weight gain
Fractional turnover per day 10% 60%
Weakness, increased DTRs Stiffness, decreased DTRs
Metabolic clearance per day 1.1L 24L
Half-life(biologic) 7 days 1 day
Drug MOA
Serum levels 4.8-10.4mcg/dL 60-181ng/dL
Propylthiouracil Block thyroid hormone synthesis
Total (62-134nmol/L) (0.92-2.79nmol/L)
Free 0.8-2.7ng/dL 230-420pg/dL Potassium iodide Retards release of thyroid hormone
(10.3-34.7pmol/L) (3.5-6.47pmol/L)
Propranolol* Control severe cardiovascular manifestations
Amount bound 99.96% 99.6% (hypertension and tachycardia)
Biologic potency 1 4 Hydrocortisone Protects against shock;
Block the conversion of T4 to T3
Oral absorption 70% 95%
Diltiazem If β blockers* are contraindicated by the presence
Absorbed in Majority are absorbed in duodenum and
of severe heart failure or asthma(Katzung, 14th ed., p.699)
ileum particularly T4

TERMS DEFINITION Factors (+) TRH(thyroid releasing hormone) release

T3 and T4 ● metabolized through phase 2 Psychosis
 Cold temperatiure
Phase 2 conversion of drugs to a more polar  Circadian and Pulsatile rhythm
metabolite for drug excretion (acetylation,
glucuronidation, conjugation) ● Function of thyroid hormones
conjugated with glucuronide or sulfate

Function of thyroid ● Regulation of metabolism

 DIABETES
Non-Insulin Drug Group Drugs
Biguanides Metformin, Buformin
Exenatide, Liraglutide,
GLP-1 receptor agonists Lixisenatide, Semaglutide,
Dulaglutide, Albiglutide
Dapagliflozin, Canagliflozin,
SGLT2 inhibitors
Empagliflozin
Sitagliptin, Vildagliptin,
DPP-4 inhibitors Saxagliptin, Linagliptin,
Teneligliptin, Alogliptin
Alpha-glucosidase inhibitors Acarbose, Voglibose, Miglitol
Thiazolidinediones Rosiglitazone, Pioglitazone
Glyburide/ Glibenclamide,
Sulfonylureas Gliclazide, Glimepiride,
Glipizide, Gliquidone
Other insulin secretagogues Repaglinide, Nateglinide
Bile acid sequestrants Colesevelam
Amylin agonists Pramlintide
Dopamine agonists Bromocriptine QR

Table 1. Non-insulin DM Medications

NON-INSULIN DM MEDICATIONS
Drug Group Biguanides GLP-1 Agonist SGLT-2 iNH DPP-4 iNH α-Glucose iNH TZDs Sulfonylurea (SU)
Drugs Metformin Liraglutide Empagliflozin Sitagliptin Acarbose Thiazolidione Gliclazide
(Pioglitazone)
“Matt-formin” “Laura-glutide” “Em-Pat-gliflozin” “Shiela-gliptin” “Eri-Carbose” “Thea-zolidione” “Gly-clazide”
M MOA ⬆️activity of AMP- Main action on Inhibit dipeptidyl Delays the 1o: promotes
E dependent protein incretin effect peptidase-4 digestion and glucose uptake and Insulin
C kinase → ⬇️hepatic Long acting (degrades incretins) absorption of starch utilization secretagogues:
H & renal Subcutaneous → ⬆️GLP-1 & GIP and disaccharides 2o: reduce hepatic release of insulin
A gluconeogenesis Slows gastric levels glucose production from pancreatic
N emptying and inhibits lipolysis beta cells
I Ppar -y
S TAG lowering
M effects
Beta-cells = major major
⬆️insulin
secretion
Incretin = ⬇️ major
incretin
effect
Alpha-cells Reduction of major
= plasma glucagon
⬆️glucagon
secretion
Fat = + fatty acid
⬆️lipolysis oxidation
Reduces
lipogenesis
Muscle = major major
⬇️glucose
uptake
Liver = Major
⬆️hepatic Decreases hepatic
glucose gluconeogenesis
production
Brain =
brain
dysfunction
(⬆️appetite,
⬇️morning
dopamine
surge,
⬆️sympatheti
c tone)
Colon = Inc glucose to
abnormal lactate in
microbiota enterocytes
increase GLP
secretion
Immunity =
immune
 dysregulatio
n/inflammati
on
Stomach = Slowing of glucose major
⬆️rate of absorption from GI
glucose tract
absorption
Kidney = major
⬆️glucose
reabsorption
Summary increased glycogen 2, 1,3,6,7 11 1, 3, 2, 6 10, 2 5, 4, 6 1
storage, decreased
hepatic glucose
production, increased
insulin sensitivity
** no pancreatic effect
MNEMONIC: Bobo, I Almost Forgot My Laptop & Bag in my Condo... ISKrrrrt!
1. Beta-cells = ⬆️insulin secretion 7. Brain = brain dysfunction (⬆️appetite, ⬇️morning dopamine surge, ⬆️sympathetic tone)
2. Incretin = ⬇️incretin effect 8. Colon = abnormal microbiota
3. Alpha-cells = ⬆️glucagon secretion 9. Immunity = immune dysregulation/inflammation
4. Fat = ⬆️lipolysis 10. Stomach = ⬆️rate of glucose absorption
5. Muscle = ⬇️glucose uptake 11. Kidney = ⬆️glucose reabsorption
6. Liver = ⬆️hepatic glucose production
 Biguanides GLP-1 Agonist SGLT-2 iNH DPP-4 iNH α-Glucose iNH TZDs Sulfonylurea (SU)
Metformin Liraglutide Empagliflozin Sitagliptin Acarbose Thiazolidione Gliclazide
(Pioglitazone)
Glucose Hypoglycemia Hypoglycemia
(if w/ SU)
Weight Slight loss Loss (suppress Loss Neutral GAIN GAIN
apetite)
Renal/ GU CI: GFR <30 mL/ CI: CrCl <30 CI: eGFR <45 mL/ Dose adjustment ⬆️Hypo risk ⬆️Hypo risk
min/1.73m2📍 (Exenatide) min/1.73m2 (except Linagliptin)

Potential Benefit of LA I: eGFR <45 mL/ Effective in ⬇️

GLP1-RA min/1.73m2 w/ CKD3 + Albumunuria
albuminuria
(Canaglilozin)

⬆️risk of UTI
(internally) & genital
vaginal mycotic
infection (externally)

Potential CKD benefit

EMPAGLIFLOZIN
better than liraglutide in
reducing nephropathy

GI Sx Moderate Moderate Moderate (Flatulence,

(nausea, metallic (nausea, vomiting, diarrhea, abdominal
taste, dyspnea)📍 diarrhea) pain)
♥️CHF Prevent HF Increased risk of ♥️ Moderate CHF risk fluid retention,
Potential benefit for LA Hospitalization failure seen with increased risk of ♥️
GLP1-RA (CANAGLIFLOZIN, Saxagliptin and failure
DAPAGLIFLOZIN) Alogliptin (Compendium)

Manage HFrEF
(Dapagliflozin)
E ♥️ASCVD CV death reduction 22% RR CVD death ⬇️CV mortality Possible ⬆️ May reduce stroke risk CVD risk (except
liraglutide (Emgpaliflozine) hospitalizations for ♥️ Gliclazide)
F failure (Alogliptin &
F ⬇️MACE events Saxagliptin)
E (Canagliflozin)
C Bone ⬇️bone mineral
T density (prone to
S fractures)
Keto- neutral DKA can occur in
acidosis various stress settings
Hypogly neutral

Other Necrotizing and Nasopharyngitis; Risk of bladder cancer

ADRs hemorrhagic Dehydration
pancreatitis
Add’nal Potential anti-cancer; Mild BP improvements BP Improvements Bullous pemphigoid Flatulence 📍, Fluid retention:
Benefits Longevity; VILDAGLIPTIN diarrhea, abdominal presents as mild
PCOS; LINAGLIPTIN pain
42% DM Death anemia and
Due to undigested
reduction carbohydrate in the
peripheral
36% mortality cause colon that is then edema
68% colorectal CA Increase risk of
fermented into
reduction
20% liver CA reduce short chain fatty heart failure
67% Lung CA acids, releasing gas Contraindicated in
Elevated NYHA Class III-
transaminases IV
Almost no side
Decreased bone
effects: no renal, GU,
bone, and heart mineral density
issues; does not Prone to
cause hypoglycemia, fractures
ketoacidosis, weight (especially the
loss, weight gain elderly and
postmenopausal
women) 📣
Weight gain
Risk of bladder
cancer
B12 deficiency Nausea, vomiting and diarrhea DAPAGLIFLOZIN: adr
adr Necrotizing and hemorrhagic
● Hypoglycemia 📍
NAUSEA, METALLIC bladder ca
TASTE, DYSPNEA pancreatitis
CANAGLIFLOZIN: bone
fracture and toe
amputaiton risk
CIs Renal impairment GFR ● Significant liver ● Type I DM
<30ml/min
● GFR <45 (drug
Severe pulmo. disease ineffective) disease (ALT> ● Pregnancy
(hypoxic state leading to
● Hypotension 2.5x upper limit ● Hypersensitivity
lactic acidosis)
Decompen- sated ♥️failure ● Increased LDL- of normal) ● DKA
 Severe liver disease ● Patients at risk of ♥️
● Liver disease
Chronic alcohol abuse
C
at risk for lactic failure ● CKD (GFR <30
acidosis ● Pregnant and mL/min/1.73m
lactating

Table 2. Insulin DM Medications

INSULIN DM MEDICATIONS
Ultra-Short Acting SHORT-ACTING INTERMEDIATE-ACTING LONG-ACTING
Drug Group Aspart, Lispro, Glulisine Regular Insulin NPH Glargine, Detemir, Degludec
Drugs “Short Cha” “Regular Regi” “Neil” “Long Larry”

2 – 4 hours
Onset <0.25 0.5 – 1 hour 1 – 4 hours
1- 9 hours (Degludec)
Peak (hr) 0.5 – 1.5 2 -3 4 - 10 --
12 – 24
DOA (hr) 2-4 3-6 10 - 16
up to 42 hours (Degludec)
DM Type I or II
I
DM with liver or kidney disease,
N ✅ ✅ ✅ ✅
pregnancy
D
I Hyperglycemic emergencies ✅ ✅ ✅
C Allergies to non-insulin drugs ✅ ✅ ✅ ✅
A
T DKA ✅
I Fluctuation in insulin
O ✅
requirements
N
Perioperatively ✅
S
Insulin Prandial Basal
ADRs Hypoglycemia, lipodystrophy, allergy & immune resistance, edema, weight gain, CHF risk
SQ SQ SQ SQ
Route of Administration
IV IV
● Can be mixed with all
rapid and short-acting
● Cannot be mixed with
Other Notes insulin.
other insulins.
● Cloudy insulin – so mix
this first

SUMMARY NOTES
GENERAL ADRs
● Metformin = 1st line medication ● Hypoglycemia = Sulfonylureas, Insulin
● HbA1c 7-9% = at least dual therapy or even triple (must include metformin); ●if Break your bones = Thiazolidinediones
uncontrolled = intensify therapy ● Weight gain = Thiazolidinediones, Sulfonylurea, Insulin
BENEFITS ● Give you gas = α-glucosidase inhibitors (Acarbose)
● >9% together with catabolic symptoms of DM (weight loss, polyuria, ● Make ants attracted to your pee = Empagliflozin
polydipsia) = Insulin ● May increase CV events = Sulfonylureas (Glimepiride, Glibenclamide)
● Regardless of HbA1c, but with previous MI = Metformin + empagliflozin ⇒● Side effect from Empagliflozin - UTI + vaginal candidiasis = Metformin +
reduce risk for CV, all-cause mortality, renal outcome Liraglutide
● Indicators of high-risk or established? Atherosclerotic disease? Chronic PHARMACOKINETICS
kidney disease? Heart failure? ● Be given IV = Ultra-short-acting Insulin, Regular Insulin
○ GLP-1 receptor agonist with CVD benefits = Liraglutide
○ SGL2 inhibitor predominant CVD = Empagliflozin
○ SGL2 predominant CKD = Empagliflozin
● Weight loss = Metformin, Liraglutide, Empagliflozin
● Cheapest = Sulfonylureas, Thiazolidinediones
● Make you more sensitive to insulin = Metformin, Thiazolidinediones

Three Main 1. Decreased glucose uptake by the MUSCLES

Pathophysiologies of 2. Impaired Insulin Secretion by B-Cell in the PANCREAS resulting to deficiency
Type 2 3. Increased Hepatic Glucose Production (HGP) by the LIVER hyperglycemia in patients with Type 2
Diabetes/Triumvirate Diabetes since it produces glucose while they are sleeping.
● Insulin resistance comes FIRST in the pathophysiology of T2DM

Ominous Octet 1. Neurotransmitter dysfunction (BRAIN)

○ Reason why T2DM patients tend to eat more
2. Decreased incretin effect (INTESTINES)
3. Increased lipolysis (FAT CELLS)
4. Increased glucose reabsorption (KIDNEYS)
○ Normally, when blood sugar goes above 180mg/dL, it is secreted in the urine but in diabetic patients,
they tend to reabsorb it more📣
5. Increased glucagon secretion (PANCREAS ALPHA-CELLS)
 ○ Hyperactive alpha-cells producing a lot of glucagon

■ Glucagon
■ Secreted by the alpha-cells of the pancreas in response to low blood sugar
■ Secreted into the bloodstream going to the liver’s glucagon receptors telling the liver to produce
sugar through gluconeogenesis and glycogenolysis
6. Decreased glucose uptake
7. Decreased insulin secretion
8. Increased hepatic glucose production (HGP)

INCRETIN ● Incretin are gut hormones released from the small intestine, L cells and K cells, in response to food as an
early warning system to the pancreas 📣
○ Two incretins: glucagon-like peptide-1 (GLP- 1) and glucose-dependent insulinotropic polypeptide
(GIP)
○ Tells the pancreas to increase insulin secretion and decrease glucagon secretion
○ Degraded by an enzyme: Dipeptidyl peptidase-4 (DPP-4)
■ Very short half-life (~2-3 minutes)

Egregious Eleven (B-cell 1. Decreased insulin secretion

centric construct) 2. Decreased incretin effect (INTESTINES)
3. Increased glucagon secretion (PANCREAS ALPHA-CELLS)
4. Increased lipolysis (FAT CELLS)
5. Decreased glucose uptake (MUSCLES)
6. Increased hepatic glucose production (HGP)
7. Neurotransmitter dysfunction (BRAIN)
8. Colon/biome: abnormal microbiota; possible decreased GLP-1 secretion
9. Immune dysregulation/Inflammation
10. Stomach/small intestines: increased rate of glucose absorption

Complications in DM ● Microvascular📍
○ Diabetic retinopathy
■ Leading cause of blindness in working-age adults
○ Diabetic nephropathy
■ Leading cause of end-stage renal disease (leading to the need for dialysis)
○ Diabetic neuropathy
■ Leading cause of non-traumatic lower extremity amputations
● Macrovascular📍
○ Stroke
■ 2-4 fold increase in cardiovascular mortality and stroke
○ Cardiovascular disease
■ 8/10 diabetic parties die from CV events
○ Peripheral arterial occlusive disease
● Leads to increased risk of infections (depressed immune system)

TREATMENT GOAL INDEX GOAL

Glycemic control
HbA1c <7.0%
Preprandial capillary plasma glucose 4.4.7.2 mmol/L (80 - 130 mg/dL)
Postprandial capillary plasma <10.0 mmol/L (<180 mg/dL)
glucose
Blood Pressure < 140/90 mmHg
 ADRENAL
Approximate Relative
Potency in clinical use Duration of
Compound Action after Comments
Anti- Sodium- oral dose
inflammatory retaining
Hydrocortisone 1 1 Short Endogenous source
(Cortisol)
Cortisone 0.8 0.8 Short Cheap;inactive until
converted to Hydrocortisone
Prednisone 4 0.3 Intermedia DOC for
te Replacement Therapy
Prednisolone 5 0.8 Intermedia DOC for systemic anti-
te inflammatory and
immunosuppressive effects
Methyl- 5 0.5 Intermedia Anti-inflammatory and
prednisolone te immunosuppressive
Triamcinolone 5 0 Intermedia Relatively more toxic than
te others
Dexamethasone 30 0 Long Anti-inflammatory and
immunosuppressive, used
especially where water
retention is undesirable (e.g.
cerebral edema); DOC for
suppression of ACTH
production
Betamethasone 25-40 0 Long Anti-inflammatory and
immunosuppressive, used
especially where water
retention is undesirable
Fludro- 10 250 Short DOC for mineralocorticoid
cortisone use
Aldosterone None 500 Short Endogenous
mineralocorticoid
 TERATOGEN
TERATOGEN
STRUCTURAL FUNCTIONAL/PHYSIOLOGIC GROWTH FETAL DEATH
RETARDATION
Thalidomide Causes flipper like Phocomelia
extremities
Uses: Leprosy and
multiple myeloma
Diethylstilbestrol Abnormalities appear when
the child is older
Exposure <18 = teratogenic
- Affects male and
female
reproductive
structure
development
- Vagina and
cervical
adenocarcinoma
for female
offspring
Affects internal organs
Tobacco Cleft palate Heart abnormalities Growth restriction
Hydrocephalus Paternal smoking: fetal heart
defect
Illegal drugs Microcephaly Low IQ Growth restriction
Behavioral/cognitive impairment
Alcohol Mental retardation Growth impairment Small molecule =
Fetal alcohol syndrome crosses placenta
Diabetes mellitus Macrosomia (LGA)
Caudal regression (lower
spine did not develop)
Zika virus Microcephaly
Mercury Head, eyes, teeth Congenital Minamata disease
*avoid shark, mackerel, tile fish, malformation Mental retardation
restrict other seafood intake
Iodine radiation Microcephaly Mental retardation
*15 rads: safe
Folic acid synthesis Neural tube defect Fetal hydantoin syndrome
disruption Cardiac defec (anticonvulsant intake)
Carbamazepine Oral cleft
Lamotrigine
Phenobarbital
Phenytoin
Valproic acid

Altered fetal genetic Low levels of epoxide

composition will be toxic for the
Hydantoid baby
Carbamazepine
Phenobarbital
Altered process cell Homeobox gene malfunction
differentiation CAUSING cardiac, brain and
Retinoids cranium abnormalities
Valproic acid
VALPROIC – lowers IQ
THIOPENTAL Low lipid solubility,
**IV anesthetic for labor does not cross
plcena
Succinylcholine *highly ionized, does
*used in intubation – not cross placental
paralyzes muscles

Warfarin Crosses placenta

Insulin, heparin Large molecule
Betamethasone Prevents Fetal
respiratory distress
syndrome
Misoprostol Mobius syndrome
Paracetamol Liver toxicity if >4 g/d
NSAIDS Premature closure of Pulmonary hypertension
Ibuprofen ductus Arteriosus Bleeding (due to thromboxane
Naproxen ** prostaglandin is inhibited inhibition)
Diclofenac (prevents DA from keeping it
Piroxicam open)
Aminoglycoside Deciduous teeth Ototoxicity No adr on
GENTAMYCIN (tetracycline when used fo congenital defect
STREPTOMYCIN r>25 weeks)
TETRACYCLINE
Hydralazine
Used for preeclampsia
Nifedipine
Uses: preterm labor to
relax uterus
Beta blockrs Growth restrictions
METHYLPREDNISOLONE CLEFT PALATE
Drug Use ADR Mechanism
BENZYL ALCOHOL Bacteriostatic GASPING SYNDROME ** benzoic acid not converted
Used as injection preservatibe - Metabolic acidosis to hippuric acid
- Neurologic deterioration
- Not in adults

CHLORAMPHENICOL GRAY BABY SYNDROME No glucuronidation

- Pale, blue skin (necessary for
- Lethargic eyes chloramphenicol synthesis)
for preterm infants before 20
weeks AOG

Sulfanyl drugs Kernicterus Displace bilirubin in

SULFONAMIDE Severe jaundice newborns which increases
FREE BILIRUBIN  brain

Highly bound to plasma

proteins
CEPHALOSPORIN Dermatitis medicamentosa
CODEIN
PENICILLIN
Furosemide Nephrocalcinosis
hematuria
Tetracycline Enamel dysplasia
** not in adults
VERAPAMIL Given to infants for Series of INFANT deaths
supraventricular tachycardia (a
benefit based on adults)
DESFLURANE Adults: rapid, smooth, safe Laryngospasm
induction of anesthesia Breath holding
Hypersecretion
Furosemide Nephrocalcinosis
Indomethacin Renal Failure
Bowel perfusion
Adrenocorticoids ICP
Growth suppression
Developmental delayed
Phenytoin Thick skill
Aspirin Reye syndrome in virla fever
Valproic acid Fetal toxicity
Hyperosmolar drug Intravascular hemorrhage
Fludroquinolone Juvenile atrophy
Phenothiazine Extrapyramidal reactions
Aminoglycosides Infants less sussceptable to renal
toxicity
More on adults
Halothane Rare in children: hepatotoxicity
More on adults
Isoniazide Negligible risk of hepatitis and
jaundice in children
More on adults
Ampillicin Infantile diarrhea
Digoxin For patients with CHF Myocardial concentration is
200 times greater than in the
serum
Theophylline Serum protein binding
(infants, neonates): reduced
 narrow therapeutic
window
- Likely distributed to
extravascular
componets
- Have greater tissue
concentration (than
in adults)  greater
drug response vs
adults
GENTAMYCIN SLOWER renal elimination in
AMPICILLIN infants
DIGOXIN GFR
- Neonate: 30-40%
adult
- 3 wks: 50-60% adult
- 6-12 mos: adult
Percutaneous absorption

Hexachlorophene Brain damage and death

Aniline dye Cyanosis
Betamethasone Caused suppression of HPA
dipropionate Not for <12 yo
Mometasone furoate HPA axis suppression in infants 6-23
month old
Fluticasone Adrenal suppression
EMLA Methemoglobinemia <3week old
Lidocaine
Prilocaine
Morphine (rapid IV) Respiratory depression
Propranolol Hepatic first pass extraction
Given close to term

Phenobarbital Prevent jaundice by inducing liver

enzyme and glucuronidation
Prevent intracranial hemorrhage
Corticosteroid For lung maturation
Prevent intracranial hemorrhage
VIT K Prevent intracranial hemorrhage
PHENOBARBITAL
CORTICOSTEROIDS

FOR NEONATAL SYPHILLIS: PENICILIN AND

INFECTION BENZATHINE PENICILLIN

STREP B:
- AMPICLIN
- PCN
- CLINDAMYCIN
TOXOPLASMOSIS:
SPIRAMYCIN ND
PYRIMETHAMINE

HIV: ZIDOVUDINE

SUMMARY
Prostate CA Abarelix
Degarelix
Infertility Certorelix
Ganirelix
 Gonadotropin s(menotropin,
HCG, follitropin)
Causes hot flushes Goserelin

Oligospermia Hcg and hmg ( menotropin)

Cryptochordism Hcg

DIABETIC

Weight loss Liraglutide

No hypoglycemia Liraglutide

With hypoglycemia DPP-4 inhibitor

Good for the heart Liraglutide

empagliflozin
Renal protective Liraglutide

Low risk for CVD Simaglutide

High risk for CVD sulfonylureas

In HF risk Saxagliptin and alogliptin

rosiglitazone
No HF risk Sitagliptin
Linagliptin

Adverse effects
Multiple pregnancies Gonadotropin
Ovarian hyperstimulation Gonadotropin

Depression GnRH (cetrorelix)

Bladder cancer Dapagliflozin
Bone fractures Canagliflozin
Hepatotoxic Troglitazone
PTU
JAUNDICE METHIMAZOLE

ZONA GLUMERULOSA MINERALO CORTICOIDS Dexamethasone: least Primary

mineralocorticoid effect hyeperaldosteronism
Methylprednisolone
Fludrocortisone: more
mineralocorticoid effect

ALDOSTERONE Fludrocortisone Addison’s disease

HYDROCOTISONE
PREDNISONE
ZONA FASCICULATA GLUCOCORTICOIDS Cushing’s thinning of
Released during a stressfull event extremities
Stimulate gluconeogenesis  SE:
hyperglycemia
Stimulate protein breakdown
Stimulate lipolysis increase HSL
TOO MUCH  immunosuppressant (PLCA2
inhibition)
ACTH
ZONA RETICULARIS ANDROGENS
ACTH ACTH