Drugs Affecting the Cardiovascular System

BSN 2-2 | Group 3 (Agbayani, Ereno, Lantin, Medina, Melitante, Mendoza, Ramos, Trinidad)

OUTLINE: ANTIHYPERTENSIVE AGENTS

CHAPTER I: Antihypertensive Agents  The cardiovascular system is in charge in transporting
A. Physiology oxygenated blood to the tissues, as well as removing waste
products from them (Karch, 2011).
B. Drug Classes
a. ACE Inhibitors  It is composed of a closed system of blood vessels that has
b. Angiotensin II Receptor Blockers blood flow from high concentration to low concentration.
c. Calcium Channel Blockers  The highest pressure in the system is always the left
d. Vasodilators ventricle during systole as this is when blood is propelled
e. Other antihypertensive agents: from the aorta and into the system.
i. Diuretics  The lowest pressure is in the right atrium for this is where
ii. Renin Inhibitors all the deoxygenated blood from the body is collected.
iii. Beta Blockers  The brain releases various hormones to maintain the
iv. Alpha 1 Blockers pressure system, preventing the occurrence of
v. Alpha 2 Blockers hypertension (high blood pressure), as well as hypotension
C. Nursing Considerations (low blood pressure).
D. Summary of Prototype Drugs
PHYSIOLOGY
CHAPTER II: Antidysrhythmic Agents REVIEW OF BLOOD PRESSURE CONTROL
A. Physiology  The three determinants of the cardiovascular pressure
B. Drug Classes system:
a. Sodium Channel Blockers o Heart rate
b. Beta Blockers o Stroke volume – amount of blood propelled from
c. Potassium Channel Blockers the ventricle with each heartbeat which is primarily
d. Calcium Channel Blockers determined by the volume of blood in the system
e. Cardiotonic Agents o Total peripheral resistance – resistance of the
i. Cardiac Glycosides muscular arteries to the blood being pumped
ii. Phosphodiesterase Inhibitors through
 Small arterioles – most important factor
C. Nursing Considerations
in determining peripheral resistance;
D. Summary of Prototype Drugs they constrict
CHAPTER III: Antianginal Agents BARORECEPTORS
A. Physiology
 Specialized stretch receptors cells in the arch of the aorta,
B. Drug Classes
thin areas of blood vessels and heart chambers that
a. Nitrates respond to the degree of stretch caused by the presence of
b. Beta Blockers blood once it leaves the left ventricle through the aorta.
c. Calcium Channel Blockers
d. Angiotensin Receptor-Neprilysin Inhibitors  They can also be found in internal carotid arteries (arteries
in the neck that supply blood to the brain), and other large
C. Nursing Considerations
arteries in the neck and chest.
D. Summary of Prototype Drugs
 These cells monitor changes in pressure and stretch in the
walls of blood vessels and send impulses to the
CHAPTER IV: Antilipidemic Agents
cardiovascular center which interprets the impulses and
A. Physiology responds by sending nerve impulses to the heart and blood
B. Drug Classes vessels, therefore regulating blood pressure.
a. Bile Acid Sequestrants  The sensory input from the baroreceptors is received in the
b. HMG-CoA Reductase Inhibitors medulla in an area called the cardiovascular center or
c. Cholesterol Absorption Inhibitor vasomotor center.
d. Other lipid-lowering agents: o If the pressure is high, the baroreceptors are
i. Fibrates stretched more tightly and initiate action potentials
ii. Nicotinic acid or Vitamin B3 at a higher rate. The CV center responds by
C. Summary of Prototype Drugs increasing parasympathetic stimulation and
decreasing sympathetic stimulation which
CHAPTER V. Drugs affecting Blood Coagulation decreases cardiac rate and cardiac output. It also
A. Physiology stimulates vasodilation, which all in all, causes the
B. Drug Classes pressure in the system to drop.
a. Antiplatelet Agents o If the pressure is low, the baroreceptors are
b. Anticoagulants stretched less, and they send nerve impulses at a
c. Thrombolytic Agents slower rate to the cardiovascular center. In
d. Other drugs affecting clot formation: response, the CV center decreases
i. Low-Molecular-Weight Heparins parasympathetic stimulation of the heart while
ii. Hemorrheologic Agents increasing sympathetic stimulation of the heart
iii. Activated Protein C which causes increased secretion of epinephrine
e. Antihemophilic Agents and norepinephrine by the adrenal medulla.
f. Hemostatic Agents Therefore, increasing cardiac rate, cardiac output,
C. Summary of Prototype Drugs
 and vasoconstriction which increases total  An increase in blood pressure such that the systolic
peripheral resistance and raises the blood pressure is greater than 140 mmHg and the diastolic
pressure. pressure is greater than 90 mmHg.
 The medulla mediates these effects  To correctly diagnose hypertension, the American Heart
through the autonomic nervous system. Association has put forth new guideline for the diagnosis of
 Baroreceptors are found primarily in sinuses (small cavities) hypertension which states that a patient should have three
within the aorta and carotid arteries. consecutive blood pressure readings above normal, when
taken by a nurse, over a period of 2 to 3 weeks - it was
RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM assumed that nurses were not as threatening or stress
 A compensatory mechanism of the kidneys to ensure that provoking as doctors to avoid “White Coat Hypertension.”
blood flow is maintained. o White Coat Hypertension refers to the
 The release of renin from the juxtaglomerular cells is phenomenon wherein some patients were
caused by low blood pressure or poor oxygenation of a hypertensive only when they were in their doctor’s
nephron. office having their blood pressure measured. This
 Renin converts angiotensinogen compound into was correlated to a sympathetic stress reaction
angiotensin I inside the liver. (which elevates systolic blood pressure) and a
 Angiotensin-converting enzyme (ACE) from the alveoli tendency to tighten the muscles (isometric
metabolic cells converts angiotensin I into angiotensin II. exercise, which elevates diastolic blood pressure)
 Blood vessels constrict intensely when angiotensin II reacts while waiting to be seen and during the blood
with specific angiotensin II receptor sites. pressure measurement. These findings were
o Inc. total peripheral resistance and BP = restored recorded by researchers in the 1990s.
kidney blood flow = dec. renin release  The underlying danger of hypertension of any type is the
 Aldosterone release from the adrenal gland is stimulated by prolonged force on the vessels of the vascular system
a probable conversion of angiotensin II into angiotensin III. which can cause:
o Nephrons retain sodium and water = Increase o Thickening of the muscles in the arterial system
blood volume and blood pressure leading to a loss of responsiveness in the system.
 Osmoreceptors in the hypothalamus are stimulated by o Thickening of the left ventricle because the muscle
sodium-rich blood – causing the release of antidiuretic must constantly work hard to expel blood at a
hormone (ADH) greater force.
o Water retention in the nephrons = blood volume o The thickening of the heart muscle and the
increase increased pressure that the muscle has to
o Inc. blood vol = inc. BP = inc. kidney blood flow generate every time it contracts increase the
 Release of renin decreases, stopping the compensatory workload of the heart and the risk of coronary
mechanism. artery disease (CAD) as well.
o The force of the blood being propelled against
them damages the inner linings of the arteries,
making these vessels susceptible to
atherosclerosis and to narrowing of the lumen of
the vessels.
o Damage to tiny vessels, leading to losses of vision
(if the vessels are in the retina), kidney function (if
the vessels include the glomeruli in the nephrons),
or cerebral function (if the vessels are small and
fragile vessels in the brain).
 Untreated hypertension increases a person’s risk for the
following conditions:
o CAD and cardiac death
o Stroke
Figure 1. RAAS summarization (Karch, 2021) o Renal failure
o Loss of vision.
HYPERTENSION  Because hypertension has no symptoms, it is difficult to
 Also known as high blood pressure. diagnose and treat, and it is often called the “silent killer.”
 When a person’s blood pressure is above normal limits for  Some factors that are known to increase blood pressure in
a sustained period or having blood pressure measurements some people according to research, include high levels of
that are consistently above normal may result in a diagnosis psychological stress, exposure to high-frequency noise, a
of hypertension. high-salt diet, lack of rest, and genetic predisposition.
 Note that, all of the drugs used to treat hypertension have
Table 1. Categories Rating the Severity of Hypertension adverse effects, many of which are seen as unacceptable
by otherwise healthy people. The main reason why nurses
Blood Pressure Systolic Blood Diastolic Blood
face a difficult challenge in trying to convince patients to
Classification Pressure (mmHg) Pressure (mmHg)
comply with their drug regimens when they experience
Normal <120 And <80
adverse effects and do not see any positive effects on their
Prehypertension 120-139 Or 80-89
bodies.
Stage 1 Hypertension 140-159 Or 90-99
Stage 2 Hypertension 160 Or 100
 THERE ARE TWO TYPES OF HYPERTENSION: STEPPED-CARE APPROACH
Essential Hypertension  Established by the Seventh Joint National Committee on
 Hypertension with no known cause, however, contributing Prevention, Detection, Evaluation, and Treatment of
factors may include family history of hypertension, Hypertension (National Institutes of Health).
hyperlipidemia, African-American background, diabetes, o Published an algorithm for the treatment of
aging, stress, excessive alcohol ingestion, smoking, and hypertension to help prescribers select an
obesity. antihypertensive agent in light of complicated
 The most common type of high blood pressure affecting conditions
90% of persons with high blood pressure.  If hypertension is controlled, patient will have a reduced risk
 For most people who get this kind of blood pressure, it of cardiovascular death and disease
develops over time as you get older.  The risk of developing cardiovascular complications is
directly related to the patient’s degree of hypertension as
 People with essential hypertension usually have:
seen in Table 1.
o Elevated total peripheral resistance.
o Their organs are being perfused effectively  Chronic conditions complicate hypertensive treatment
o They usually display no symptoms.  Drug choice varies among individuals as our body responds
differently – an effective combination of antihypertensive
Secondary Hypertension drugs on one person may not be that effective to another.
 High blood pressure resulting from a known cause or is
ACE INHIBITORS
caused by another medical condition or use of certain
medicines. THERAPEUTIC ACTIONS
 10% of hypertension cases are related to renal and  Angiotensin-converting enzyme inhibitors (ACEIs) are
endocrine disorders. medications that help relax the veins and arteries to lower
 It usually gets better after the condition is treated or the blood pressure by helping constricted blood vessels expand
client stopped taking the medicines that are causing it. to let more blood through.
 Example, a tumor in the adrenal medulla called a  Physiologically, the conversion of angiotensin I to
pheochromocytoma can cause hypertension related to the angiotensin II happens in the lungs as the metabolic cells
release of large amounts of norepinephrine from tumor of the alveoli use angiotensin-converting enzyme (ACE) to
cells, which was resolved after the tumor is removed. convert angiotensin I to angiotensin II.
 Thus, ACEIs act in the lungs to prevent ACE from
HYPOTENSION converting angiotensin I to angiotensin II, ultimately
 Occurs when blood pressure is too low reducing the production of angiotensin II.
 A condition that can progress to shock causing waste  Note that, angiotensin II is a substance that is known to be
products to accumulate and cell death due to the lack of a powerful vasoconstrictor and stimulator of aldosterone
oxygen release.
 Hypotension occurs in the following situations:  If aldosterone is released, it promotes sodium and water
o Inability of heart to pump effectively due to heart retention which causes fluid volume increase that elevates
muscle damage. blood pressure and forces the heart to work harder.
o Blood volume drops due to severe blood loss.  As the conversion of angiotensin I to angiotensin II is
o Inability of the body to respond to stimuli when inhibited by this drug, thus vasoconstriction and
blood pressure drops due to norepinephrine aldosterone released are blocked, which leads to a
depletion and extreme stress. decrease in blood pressure, excretion of water and sodium,
and potassium retention.
ANTIHYPERTENSIVE AGENTS
INTRODUCTION INDICATIONS
 Because an underlying cause of hypertension is usually  Indicated for the treatment of hypertension, alone or in
unknown, altering the body’s regulatory mechanisms is the combination with other drugs.
best treatment currently available and drugs used to treat  However, they can also be used in conjunction with digoxin
hypertension work to alter the normal reflexes that control and diuretics for the treatment of left ventricular dysfunction.
blood pressure.
 Treatment for essential hypertension does not cure the CONTRAINDICATIONS AND CAUTIONS
disease but is aimed at maintaining the blood pressure  Patients with allergy to any of the ACE inhibitors and with
within normal limits to prevent the damage that impaired renal function, which could be exacerbated by the
hypertension can cause. effects of this drug in decreasing renal blood flow.
 Note that, not all patients respond in the same way to  Patients with heart failure because the change in
antihypertensive drugs because different factors may hemodynamics could be detrimental in some cases and in
contribute to each person’s hypertension. those with salt/volume depletion, which could be
 Antihypertensive agents include angiotensin-converting exacerbated by the drug effects.
enzyme inhibitors (ACEIs), angiotensin II–receptor blockers  Women of childbearing age who choose to use one of these
(ARBs), calcium channel blockers, vasodilators, and other drugs should be encouraged to use barrier contraceptives
antihypertensive agents, including diuretic agents, to avoid pregnancy while taking the drug.
ganglionic receptors, renin inhibitors, and sympathetic  Pregnant women due to potential for serious adverse
nervous system drugs. effects on the fetus and during lactation because of
potential decrease in milk production and effects on the
neonate.
 This group of drugs should not be taken with potassium-
sparing diuretics such as spironolactone (Aldactone) or salt
 substitutes that contain potassium, because of the risk of  Pregnant women as it is associated with serious fetal
hyperkalemia (serum potassium excess). abnormalities and even death.
 Lactating women, even though it is not known whether the
DRUGS UNDER ACE INHIBITORS ARBs enter breast milk during lactation, these drugs should
 benazepril (Lotensin) not be used during lactation because of the potential for
 captopril (Capoten) serious adverse effects in the neonate.
 enalapril (Vasotec)
DRUGS UNDER ANGIOTENSIN II
 enalaprilat (Vasotec IV)
 fosinopril (Monopril)  candesartan (Atacand)
 lisinopril (Prinivil, Zestril)  eprosartan (Teveten)
 moexipril (Univasc)  irbesartan (Avapro)
 perindopril (Aceon)  losartan (Cozaar)
 quinapril (Accupril)  olmesartan (Benicar)
 ramipril (Altace)  telmisartan (Micardis)
 trandolapril (Mavik)  valsartan (Diovan)

ANGIOTENSIN II RECEPTOR BLOCKER (ARB) CALCIUM CHANNEL BLOCKERS

THERAPEUTIC ACTION THERAPEUTIC ACTIONS
 Angiotensin II-Receptor Blockers (ARBs) are medications  Decrease blood pressure, cardiac workload, and
that block the action of angiotensin II by preventing myocardial oxygen consumption.
angiotensin II from binding to angiotensin II receptors on the  May also manage chronic stable angina.
muscles surrounding blood vessels and adrenal cortex  Inhibit the movement of calcium ions across myocardial
causing vasodilation and decrease peripheral resistance. membranes and arterial muscle cells = alteration of action
potential and blocking muscle cell contraction
 Note that,
o Myocardial contractility depression
o The hormone angiotensin II has a powerful
o Slows cardiac impulse formation in the conductive
constricting effect on blood vessels, increasing
tissue
blood pressure.
o Relaxation and dilation of arteries = dec. BP and
o Angiotensin II also stimulates salt and water
dec. venous return
retention in the body, due to the stimulation of
aldosterone release, which further increases blood
INDICATIONS
pressure.
 So, ARBs work by blocking receptors or by selectively  Extended-release forms treat hypertension in adults
binding with the angiotensin II receptors in vascular smooth o May be used as monotherapy or as part of
muscle and in the adrenal cortex that the hormone acts on, combination therapy
specifically AT1 receptors, which are also found in the  IV forms for short-term use only when oral route is not
heart, blood vessels and kidneys. feasible
 Blocking the action of angiotensin II helps to lower blood  Other preparations are used for angina and treating various
pressure brought by effects of RAA system and prevent arrhythmias in adults
damage to the heart and kidneys and help widen blood  Coronary spasm
vessels to allow blood to flow more easily.  Supraventricular dysrhythmias
 ARBs are generally prescribed for people who cannot  Hypertrophic cardiomyopathy
tolerate ACE inhibitors.  Pulmonary Hypertension
Other indications:
 Angiotensin II receptor blockers (ARBs) have similar effects
o Raynaud phenomenon
as ACE inhibitors, but work by a different mechanism.
o Subarachnoid hemorrhage
ARBs block the effect of angiotensin II while ACEIs
o Migraine headaches
reduce the production of angiotensin II.
CONTRAINDICATIONS AND CAUTIONS
INDICATIONS
 Presence of allergy – cause hypersensitivity reactions
 ARBs are indicated to be used alone or in combination
 Heart failure with reduced ejection fraction / blockage / sick
therapy for the treatment of hypertension and for the
sinus syndrome – worsens through the conduction-slowing
treatment of heart failure in patients who are intolerant to
effects of the drug
ACE inhibitors.
 Renal or hepatic dysfunction – alter metabolism and
 Recently, they also were found to slow the progression of excretion of the drug
renal disease in patients with hypertension and type 2
 Pregnancy (unless benefit outweighs potential risk) – pose
diabetes.
potential serious adverse effects on the fetus
o During neonatal period, another method of feeding
CONTRAINDICATIONS AND CAUTIONS
must be utilized if CCB is taken by the mother
 Patients with allergies to any of these drugs to prevent
hypersensitivity reactions. DRUGS UNDER CCB
 Caution should be used in the presence of hepatic or renal IMMEDIATE-RELEASE AND SUSTAINED RELEASE FORMS:
dysfunction, which could alter the metabolism and excretion  amlodipine (Norvasc)
of these drugs, and with hypovolemia, because of the
 felodipine (Plendil)
blocking of potentially life-saving compensatory
 isradipine (DynaCirc, DynaCirc CR)
mechanisms.
 nicardipine (Cardene, Cardene SR)
SUSTAINED-RELEASE OR EXTENDED-RELEASE FORMS: INDICATIONS
 diltiazem (Cardizem Dilacor CR)  This drug is commonly either used alone or as a part of
 nifedipine (Procardia XL) combination therapy for hypertensive treatment in adults.
 nisoldipine (Sular)  If proven the benefit outweighs risk, this drug can be taken
 verapamil (Calan SR) by pregnant women only until the end of their first trimester.
 Women of childbearing age using this drug should apply
VASODILATORS contraceptive measures while on this drug.
THERAPEUTIC ACTIONS CONTRAINDICATIONS
 These drugs act directly on vascular smooth muscles to  For pregnant women, this drug crosses the placenta and
yield muscle relaxation, which can cause vasodilation and enters the breast milk – therefore, it should be avoided if
drop the blood pressure, and they do not inhibit the reflex women are in their second and third trimesters of
tachycardia that occurs afterwards. pregnancy.
 Usually, these drugs are administered when a patient has  Breastfeeding women should find other methods of feeding
severe hypertension and has not responded to other the baby if the drug is gravely needed.
therapy.
SYMPATHETIC NERVOUS SYSTEM BLOCKERS
INDICATIONS  Drugs that block the effects of the sympathetic nervous
 Treatment of hypertensive crisis in hospitalized or non- system are useful in blocking many of the compensatory
hospitalized adults effects of the sympathetic nervous system and includes
o May also be used for patients who are Beta Adrenergic Blockers/Antagonists (BBs), Alpha1 (ᾀ1)
unresponsive to other therapy Adrenergic Blockers/Antagonists, and Alpha2 (ᾀ2)
 Maintain controlled hypotension during surgery Adrenergic Agonists.

CONTRAINDICATIONS AND CAUTIONS BETA BLOCKERS

 Presence of allergy – cause hypersensitivity reactions and  Beta-adrenergic receptors (β-ARs) are adrenergic
could worsen into a sudden fall of blood pressure (cerebral receptors (which means it binds both norepinephrine and
insufficiency) epinephrine) in the sympathetic nervous system.
 Patients with peripheral vascular disease, CAD, heart  These receptors are further classified into subtypes— β1,
failure, and tachycardia – drug could worsen the following β2, β3—based on the specific responses they elicit and by
conditions by the drop in blood pressure their selective binding of drugs that activate or block them.
 Functional hypoglycemia – Diazoxide can antagonize  β-ARs belong to the superfamily of G protein-coupled
insulin by increasing glucose levels receptors (GPCRs) and their signaling pathway is
 Pregnancy (unless benefit outweighs risk) – pose potential stimulated by the endogenous catecholamines,
serious adverse effects on the fetus epinephrine and norepinephrine (Brodde, 2008).
o During neonatal period, another method of feeding
must be utilized if the drug is taken by the mother β-ARs MAJOR LOCATION EFFECTS UPON
ACTIVATION
DRUGS UNDER VASODILATORS
 nitroprusside (Nitropress) Cardiac muscle fibers Increased force and rate of
 hydralazine (Apresoline) contraction
 minoxidil (Lonten)
 nitroprusside (Nitropress) Juxtaglomerular cells of Renin secretion.
kidneys
OTHER DRUGS
DIURETICS Posterior pituitary Antidiuretic hormone (ADH)
secretion
 Diuretics are drugs that increase the excretion of sodium
and water from the kidney and are very important for the
treatment of hypertension. Adipose cells Breakdown of triglycerides
→ release of fatty acids into
 These drugs are often the first agents tried in mild
blood
hypertension as they affect blood sodium levels and blood
volume.
Smooth muscle in walls Inhibition → relaxation,
 Although these drugs increase urination and can disturb
of airways; in blood which causes dilation of
electrolyte and acid–base balances, they are usually
vessels that serve heart, airways, vasodilation, and
tolerated well by most patients.
skeletal muscle, adipose relaxation of organ walls.
tissue, and liver; and in
RENIN INHIBITORS
walls of visceral organs,
THERAPEUTIC ACTIONS such as urinary bladder.
 Directly inhibits renin which leads to decreased plasma
renin activity, and therefore, inhibits the conversion of
angiotensinogen to angiotensin I. Ciliary muscle in eye. Inhibition → relaxation.
 The inhibition of the enzyme conversion leads to the
general inhibition of the renin-angiotensin-aldosterone
system, decreasing blood pressure, aldosterone release,
as well as sodium reabsorption.
 The GI tract slowly absorbs this, is then metabolized in the
liver, and then excreted in the urine.
 bisoprolol, and metoprolol were only
Hepatocytes in liver Glycogenolysis (breakdown partially effective. Studies also show that
of glycogen into glucose). at the upper end of the dosage range,
cardioselectivity is less effective.
 The real value of beta selectivity is in
Brown adipose tissue Thermogenesis (heat maintaining renal blood flow and
β3 production) minimizing the hypoglycemic effects of
beta blockade.
Table 2. Beta blockers’ major location and effects.
 Beta-adrenergic blockers, frequently called beta blockers, Indications
are used as antihypertensive drugs or in combination with  Beta adrenergic blockers are indicated to be used alone or
a diuretic. However, these drugs have many adverse in combination therapy with diuretics for the treatment of
effects and are not recommended for all people. They are hypertension and myocardial infarction, antidysrhtymic, and
often used as monotherapy in step 2 treatment, and in some anti-anginals.
patients they control blood pressure adequately.  β-Blockers are equally effective at reducing blood pressure
but are associated with a higher incidence of stroke than
Therapeutic Action other drugs. They are no longer preferred for uncomplicated
 Beta-adrenergic blockers block vasoconstriction, decrease hypertension but may be used if there are additional
heart rate, lowers blood pressure, decrease cardiac muscle indications, e.g. patients with angina, heart failure, or
contraction, and tend to increase blood flow to the kidneys, following myocardial infarction.
leading to a decrease in the release of renin.
 Beta blockers work by blocking the effects of the hormone Contraindications
epinephrine, also known as adrenaline, resulting in the  Hypersensitivity to the drug.
inhibition of chronotropic and inotropic effects on the heart  Bronchospastic lung disease as beta blockade can induce
causing the heart to beat more slowly and with less force, bronchospasm in patients with bronchospastic lung
which lowers blood pressure. disease. For this reason, these agents should be avoided
 In addition to this, beta-blockers also decrease blood in patients with severe lung disease.
pressure via several mechanisms, including decreased  Second-degree and complete heart block, sick sinus
renin and reduced cardiac output. syndrome, or symptomatic bradycardia from any cause as
o Note that, generally, activation of beta-receptors in patients with high grade heart block or symptomatic
a fight or flight response increases heart rate and bradycardia can develop severe bradycardia and
stimulates cardiac contraction (thereby increasing hypotension with administration of beta-blocking agents. In
cardiac output), dilates the bronchi (thereby some cases, pacemaker therapy may be considered to
increasing air flow into and out of the lungs), allow such patients to derive the benefits of beta-blocker
dilates the blood vessels to improve blood flow, therapy.
and relaxes the uterus. But since BBs block these,  Cardiogenic shock or severe decompensated heart failure.
it causes the heart to work less and slowly, Although long-term benefit can be derived from blockade of
ultimately lowering the blood pressure. sympathetic and catecholamine beta adrenergic
 There are many types of beta blockers some of which stimulation, these mechanisms provide important short-
includes: term circulatory and ventricular contractile support in acute
o Nonselective beta blockers are BBs which bind exacerbations of heart failure. Therefore, beta-blockers
to all types of beta receptors and prevents their should not be initiated in these settings.
activation by epinephrine and norepinephrine. It  Caution should be exhibited to patients with hepatic, renal,
inhibits beta1 (heart) and beta2 (bronchial) or thyroid dysfunction, asthma, peripheral vascular disease
receptors from activating and eliciting their effects. and diabetes mellitus type 1.
Since the activation is blocked, this results in
decreased heart rate and force of contraction and Drugs under Beta-Adrenergic Blockers
a consequent decrease in blood pressure. Non-selective Beta-Blockers
However, undesired effects due to blockade of  propranolol (Inderal)
beta2 receptors may include hypoglycemia (low
blood glucose), resulting from decreased glycogen  sotalol
breakdown and decreased gluconeogenesis (the  labetalol
conversion of a non-carbohydrate into glucose in  carvedilol (Coreg)
the liver), and mild bronchoconstriction (narrowing
of the airways). Cardioselective Beta-Blockers
o Cardioselective beta blockers act mainly on the  acebutolol (Sectral)
beta1 rather than the beta2 receptors which  atenolol (Tenormin)
reduces the possibility of bronchoconstriction to  betaxolol (Kerlone)
occur – the main reason why it is more preferred
 bisoprolol (Zebeta)
than the non-selective ones.
 However, cardioselectivity does not  metoprolol (Lopressor)
confer absolute protection from
bronchoconstriction. In tests measuring ALPHA1-BLOCKERS
forced expiratory volume in 1 second Therapeutic Action
(FEV1) as a measure of β− reactivity,  Has the ability to block postsynaptic alpha1-receptor sites,
only atenolol demonstrated true and is therefore used to treat hypertension.
protection. Other cardioselective beta o Decreases vascular tone and promotes
blockers, such as acebutolol, betaxolol, vasodilation, yielding low blood pressure
  They do not block the presynaptic alpha2-receptor sites,
and therefore decreases blood pressure due to the non- Drugs under Alpha2-Agonists
occurrence of reflex tachycardia.  clonidine
 methyldopa
Drugs under Alpha1-blockers  guanabenz
 doxazosin (Cardura)  guanfacine
 prazosin (Minipress)  lofexidine
 terazosin (Hytrin)
NURSING CONSIDERATIONS
ALPHA2-AGONISTS ASSESSMENT
Therapeutic Action  Note for patient’s history of allergies to antihypertensive
 Centrally acting alpha2 agonists stimulate the alpha2 - medications or its components
receptors in the CNS and inhibit the cardiovascular centers,  Pregnancy or lactation
leading to a decrease in sympathetic outflow from the CNS  CV: Blood pressure, pulse, perfusion, baseline ECG
and a resultant drop in blood pressure.  CNS: Orientation, affect
 Specifically, alpha2 agonists decrease the sympathetic  Skin: Color, lesions, texture, temperature
response from the brainstem to the peripheral vessels.
 Respi: Respiration, adventitious breath sounds
 They stimulate the alpha2 receptors, which in turn
 GI: Abdominal examination, bowel sounds
decreases sympathetic activity, increases vagus activity,
 Lab Tests: Renal and liver function tests, CBC, electrolyte
decreases cardiac output, and decreases serum
levels, blood glucose levels
epinephrine, norepinephrine, and renin release.
 Baseline status including weight.
 Centrally acting alpha2 agonists treat hypertension by
relaxing the blood vessels which lowers blood pressure and
DIAGNOSIS
heart rate, and when the blood pressure is lowered, the
amount of blood and oxygen going to the heart is increased.  Ineffective tissue perfusion (total body) r/t changes in
 In other words, it allows blood to flow more easily through cardiac output
the body. All of these actions result in reduced peripheral  Impaired skin integrity r/t dermatological effects
vascular resistance and increased vasodilation. Thus, this  Acute pain r/t GI distress, skin effects, or headache
medicine will not cure high blood pressure, but it does help  Deficient knowledge regarding drug therapy
control it.
 However, these drugs are associated with many adverse IMPLEMENTATION
CNS and GI effects, as well as cardiac dysrhythmias.  Encourage lifestyle changes to increase drug effectiveness
 Do not cut, crush, or chew tablet, and give with food if GI
Indications upset occurs
 Centrally acting alpha2 agonists are indicated to be used to  Reduce dosage if pt has renal failure
treat hypertension and ADHD.  Monitor for any situation that might lead to a drop in BP
 Monitor blood glucose and serum electrolytes.
Contraindications  Monitor any situation that mays lead to a drop in fluid
 The alpha-specific adrenergic agonists are contraindicated volume.
in the presence of:  Provide comfort measures, support, and reassurance to
o Allergy to the specific drug to avoid deal with drug effects
hypersensitivity reactions.  Provide thorough pt teaching regarding drug, dosage,
o Severe hypertension or tachycardia because of adverse effects, s/sx of problems to report, and safety
possible additive effects. precautions.
o Narrow-angle glaucoma, which could be
exacerbated by arterial constriction EVALUATION
 They should be used with caution in the presence of:
o Cardiovascular disease or vasomotor spasm  Evaluate drug effects: maintenance of BP w/in normal limits
because these conditions could be aggravated by  Monitor for adverse effects: nausea, dizziness;
the vascular effects of the drug. hypotension, congestive heart failure, skin reactions
o Thyrotoxicosis or diabetes because of the thyroid-  Monitor for drug-drug interactions as listed
stimulating and glucose-elevating effects of  Evaluate effectiveness of pt teaching program and comfort
sympathetic stimulation. and safety measures
o Renal or hepatic impairment, which could interfere
with metabolism and excretion of the drug.
 DRUG CLASSES
CAPTOPRIL (CAPOTEN)
ACE INHIBITOR

GENERIC NAME captopril

TRADE NAME Capoten

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Treatment of hypertension, adjunct therapy for heart failure, treatment of left ventricular dysfunction after myocardial
INDICATIONS
infarction (MI), and diabetic nephropathy.
Captopril comes as a tablet to take orally. It is usually taken two or three times a day on an empty stomach, 1 hour before
a meal.
DOSAGE &  25 mg PO b.i.d. to t.i.d. for hypertension
FORMS  50–100 mg PO t.i.d. for heart failure (HF)
 50 mg PO t.i.d. for ventricular dysfunction
 25 mg PO t.i.d. for diabetic nephropathy
PHARMACOKINETICS
GI Tract
Absorption  60-75% in fasting individuals
 Food decreases absorption by 25-40% (however, some evidence indicates that this is not clinically significant)
Distribution Well-distributed
 25-30% bound to plasma proteins (primarily albumin)
Metabolism Liver

Excretion Urine

Half-life 2 hours

PHARMACODYNAMICS

Duration Varies

Onset 15 minutes

Peak
30-90 minutes
Effects

Mechanism Captopril blocks ACE from converting angiotensin I to angiotensin II, leading to a decrease in blood pressure, a decrease
of Action in aldosterone production, and a small increase in serum potassium levels, along with sodium and fluid loss.

Captopril have been detected in breast milk and are known to cross the placenta, and have been associated with serious
OTHERS
fetal abnormalities, and so they should not be used during pregnancy. (Pregnancy Category C and D)

The adverse effects most commonly to captopril are related to the effects of vasodilation and alterations in blood flow which
ADVERSE
includes tachycardia, myocardial infarction, rash, pruritus, gastric irritation, dysgeusia, proteinuria, irritated cough,
EFFECTS
unpleasant GI distress
CLINICALLY
IMPORTANT  Allopurinol - the risk of hypersensitivity reactions increases if these drugs are taken antihypertensive drugs.
DRUG-DRUG  Non-steroidal anti-inflammatory drugs – if antihypertensive drugs are taken with these kinds of drugs, there is a
INTERACTIONS risk of decreased anti-hypertensive effects

LOSARTAN (COZAAR)
ANGIOTENSIN II

GENERIC NAME losartan

TRADE NAME Cozaar

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Treatment of hypertension in adults and children 6 yrs and older. Used alone or as part of combination therapy for treatment
of hypertension in adults, slowing progression of diabetic nephropathy with elevated serum creatinine and proteinuria in
INDICATIONS
patients with hypertension and type 2 diabetes, and prevention of stroke in patients with hypertension and left ventricular
hypertrophy.
Losartan comes as a tablet to take by mouth and is usually taken once a day.
 For hypertension:
o Adults/Elderly: 25–100 mg/d PO (May increase as needed to 100 mg/day in 1–2 divided doses)
o Children (6–16 YRS): Initially, 0.7 mg/kg (maximum: 50 mg) once daily. Adjust dose to BP response.
DOSAGE & Maximum: 1.4 mg/kg or 100 mg/day
FORMS  For diabetic nephropathy:
o Adults/Elderly: Initially, 50 mg/ day. May increase to 100 mg/day based on B/P response.
 For Stroke Prevention:
o Adults/Elderly: Initially, 50 mg/ day. Maximum: 100 mg/day based on BP response. Should be used in
combination with a thiazide diuretic.
PHARMACOKINETICS

Absorption Well-absorbed in the GI Tract

Well-distributed
Distribution  Losartan is 98.6-98.8% protein bound.
 Losartan’s active metabolite (E-3174) is 99.7% protein bound in serum.
Metabolism Liver by the cytochrome P450 system.

Excretion Urine and Feces

Half-life 2 hours, then its active metabolite has a half-life of 6 – 9 hours

PHARMACODYNAMICS

Duration 24 hours

Onset Varies

Peak
1-3 hours
Effects

Mechanism Selectively and competitively blocks the binding of angiotensin II to specific tissue receptors, such as the AT1 receptors
of Action found in the vascular smooth muscle and adrenal glands. Losartan and its active metabolite bind the AT1 receptor with
1000 times more affinity than they bind to the AT2 receptor. The active metabolite of losartan is 10-40 times more potent
 by weight than unmetabolized losartan as an inhibitor of AT1 and is a non-competitive inhibitor. Together, these block the
vasoconstriction and release of aldosterone which causes vascular smooth muscle relaxation, lowering blood pressure.
 Blocks vasoconstrictor, aldosterone secreting effects of angiotensin II, inhibiting binding of angiotensin II to AT1
receptors and causes vasodilation, decreases peripheral resistance, decreases blood pressure.
Losartan can cross the placenta, has caused fetal/neonatal morbidity, mortality. However it is not known whether they enter
OTHERS
breast milk during lactation but has a high potential for adverse effects on breastfed infant.

ADVERSE Dizziness, headache, diarrhea, abdominal pain, symptoms of upper respiratory tract infection, cough, back pain, fever,
EFFECTS muscle weakness, hypotension

CLINICALLY
IMPORTANT  Phenobarbital, Indomethacin, or Rifamycin - risk of decreased serum levels and loss of effectiveness increases.
DRUG-DRUG  Ketoconazole, Fluconazole, Or Diltiazem - there may be a decrease in anticipated antihypertensive effects
INTERACTIONS

DILTIAZEM (CARDIZEM DILACOR CR)

CALCIUM CHANNEL BLOCKERS

GENERIC NAME diltiazem

TRADE NAME Cardizem Dilacor CR

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INDICATIONS Cardizem is indicated for the management of chronic stable angina as well as angina due to coronary artery spasm.

DOSAGE & Extended-release tablets: Adjusted to each of the patient’s needs, starting with 30 mg PO for QID, AC, and HS. This will
FORMS be increased gradually at 1-2-day intervals until optimum response is obtained.

PHARMACOKINETICS

Calcium channel blockers are usually taken P.O. or by mouth, and are well-absorbed in the liver. Its bioavailability is
Absorption approx. 40% with values ranging from 24-74% due to the high inter-individual variation in the first pass effect. Moreover,
the bioavailability may increase in patients with hepatic impairment.

Distribution The volume of distribution is about 7.6 ± 1.1 L/kg as most of the drug – approximately 70%, is protein bound.

Metabolism Extensively metabolized by the liver

Excretion Excreted by the kidneys and in bile

Half-life Various studies have debated over whether it is 2.3 hours or 4.2 hours.

PHARMACODYNAMICS

Duration 12 hours

Onset 30-60 minutes

Peak
6-11 hours
Effects

This drug mainly inhibits the transfer of calcium ions across the membranes of both the cardiac and arterial muscle cells,
Mechanism
which lowers the rate of influx. This then results to slowed conduction of the heart, decreased myocardial contractility, as
of Action
well as dilation of arterioles – yielding the lowering of blood pressure and decreasing myocardial oxygen consumption.
OTHERS

This is related to the drug’s effect on the smooth muscle and cardiac output of the heart. This include:

ADVERSE  Integ: Skin flushing and rashes

EFFECTS  CNS: Dizziness, Light-headedness, Headache, Fatigue
 GI: Nausea, and Hepatic injury r/t direct toxic effects on hepatic cells
 CV: Hypotension, Bradycardia, Peripheral edema, and Heart blockage

CLINICALLY
IMPORTANT This varies with each of the calcium channel blockers used to treat hypertension. One thing we must take note of is the
DRUG-DRUG increase in serum levels and the possible toxic effects of cyclosporine if it is taken with diltiazem
INTERACTIONS

NITROPRUSSIDE (NITROPRESS)
VASODILATOR

GENERIC NAME nitroprusside

TRADE NAME Nitropress

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 Sodium nitroprusside is indicated for the immediate reduction of blood pressure of adult and pediatric patients in
hypertensive crises. Concomitant longer-acting antihypertensive medication should be administered so that the
INDICATIONS duration of treatment with sodium nitroprusside can be minimized.
 Sodium nitroprusside is also indicated for producing controlled hypotension in order to reduce bleeding during
surgery.
 Sodium nitroprusside is also indicated for the treatment of acute congestive heart failure.
DOSAGE &
IV Infusion: 3 mcg/kg per minute – do not exceed 10 mcg/kg per minute. (IV)
FORMS

PHARMACOKINETICS

Absorption Not available

Distribution Not available

Metabolism Metabolized in the liver

Excretion Excreted through urination

Half-life Approximately 2 minutes

PHARMACODYNAMICS
 Duration 1-10 minutes

Onset 1-2 minutes

Peak
Rapid
Effects

Mechanism It acts directly on vascular smooth muscle to cause vasodilation and drop of blood pressure. Renin release will occur as
of Action this drug does not inhibit cardiovascular reflexes, as well as tachycardia.

OTHERS

These effects are related to changes in blood pressure such as:

 CNS: Dizziness, Anxiety, Headache
ADVERSE  CV: Reflex tachycardia, Heart failure, Chest pain, Edema
EFFECTS  Integ: Skin rash and lesions (abnormal hair growth with minoxidil)
 GI: GI upset, Nausea, and Vomitting
 Cyanide toxicity: Dyspnea, Headache, Vomiting, Dizziness, Ataxia, Loss of consciousness, Imperceptible pulse,
Absent reflexes, Dilated pupils, Pink color, Distant heart sounds, and shallow breathin

CLINICALLY
IMPORTANT Generally, each drug under this subclass work differently in the body – and therefore must be thoroughly checked before
DRUG-DRUG administering.
INTERACTIONS

ALISKIREN (TEKTURNA)
RENIN INHIBITOR

GENERIC NAME aliskiren

TRADE NAME Tekturna

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This drug is indicated for treatment of hypertension in pediatric patients weighing 50 kg or greater, who are at least 6 years
INDICATIONS of age to lower blood pressure – as lowering blood pressure reduces the risk of both fatal and nonfatal cardiovascular
circumstances like stroke and/or myocardial infarction.

DOSAGE & Tablet: 150 mg PO once a day PC, depending on blood pressure response. If blood pressure remains uncontrolled,
FORMS proceed with a higher dosage (300 mg).

PHARMACOKINETICS

Slowly absorbed in the GIT with a bioavailability between 2.0-2.5%. Meanwhile, peak plasma concentrations are successful
Absorption at 1-3 hours-time post-administration. Moreover, the steady-state concentration of the drug is achieved within 7-8 days of
regular administration

Distribution Unchanged aliskiren accounts for about 80% of the drug found in plasma contents.

PO – 80% of the drug in the plasma remains unchanged as two major metabolites account for about 1-3% of the drug in
Metabolism
the plasma.

Hepatobiliary route is the excretion site of the drug wherein approx. one-quarter of the absorbed dose is shown in the urine
Excretion
as an unchanged parent drug.

Half-life 24 hours.
PHARMACODYNAMICS

Duration 30-40 hours

Onset Within 2 weeks

Peak
3 hours
Effects

Mechanism This directly inhibits renin which decreases plasma renin activity, therefore inhibiting the conversion of angiotensinogen to
of Action angiotensin I.

This drug crosses the placenta and enters the breast milk, and should be avoided in the second and third trimesters of
OTHERS
pregnancy.

ADVERSE
Diarrhea
EFFECTS

CLINICALLY
 Cyclosporine or Itraconazole: Avoid concomitant use
IMPORTANT
DRUG-DRUG  Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Increased risk of renal impairment and loss of antihypertensive
INTERACTIONS effect.

METOPROLOL (DUTOPROL, LOPRESSOR)

BETA BLOCKER

GENERIC NAME metoprolol

TRADE NAME Dutoprol, Kapspargo, Lopressor, Lopressor Hct, Toprol

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INDICATIONS Treatment of hypertension and myocardial infarction.
Metoprolol is available in tablets for oral administration and solution form for intravenous administration.
 For hypertension (Oral):
DOSAGE & o Adults/Elderly: 50-100 mg/d PO in 1-2 divided doses (Maintenance dose is 100 – 450 mg in divided
FORMS doses)
o Children (older than 6 years old): 1 mg/kg/d
 For Myocardial Infarction (Intravenous):
o Adults/Elderly: 5 mg q2min × 3 doses; then 25-50 mg q6h for 48 h (maint: PO: 50-100 mg b.i.d)
PHARMACOKINETICS

Absorption When metoprolol is administered orally, it is almost completely absorbed in the gastrointestinal tract.
 95% is absorbed in the GI Tract
Distribution Protein binding is 12%

Metabolism Liver

Excretion Urine

Half-life 3-7 hours

PHARMACODYNAMICS

Duration PO: 10 – 19 hours; IV: 4 – 10 hours

Onset PO: 15 minutes; IV: Immediate

Peak
PO: 1.5 hours; IV: 20 minutes
Effects
 Metoprolol is a beta1-adrenergic receptor inhibitor specific to cardiac cells as it promotes blood pressure reduction via beta 1-
Mechanism blocking effect with negligible effect on beta2 receptors. This inhibition decreases cardiac output by producing negative
of Action chronotropic and inotropic effects without presenting activity towards membrane stabilization nor intrinsic
sympathomimetics.

OTHERS Beta blockers cross the placental barrier and are excreted in breast milk.

Fatigue, weakness, dizziness, nausea, vomiting, diarrhea, mental changes, drowsiness, headache, blurred vision,
ADVERSE
photosensitivity, nasal stuffiness, impotence, decreased libido, depression, insomnia (Beta-blockers lower the secretion of
EFFECTS
melatonin).

CLINICALLY
IMPORTANT  Digitalis - increase bradycardia
DRUG-DRUG  Other antihypertensives, alcohol, and anesthetics - increase hypotensive effect
INTERACTIONS  NSAIDs - decrease effect of beta blockers
PRAZOSIN (MINIPRESS)
ALPHA 1

GENERIC NAME prazosin

TRADE NAME Minipress

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This drug is indicated for treatment of hypertension, as lowering blood pressure reduces the risk of both fatal and nonfatal
INDICATIONS
cardiovascular circumstances like stroke and/or myocardial infarction.

Should be adjusted according to the patient’s individual blood pressure response. The initial dose is usually 1 mg for BID
DOSAGE &
or TID, and may be slowly increased to a total daily dose of 20 mg given in divided doses depending on the physician’s
FORMS
order – but the optimum therapeutic doses is most commonly reached from 6-15 mg daily given in divided doses.

PHARMACOKINETICS

Bioavailability studies have shown that the total absorption correlated with the drug in a 20% alcoholic solution is 90%,
Absorption
yielding peak levels of approximately 65% of the drug in the solution – making its absorption on a moderate pace.

Distribution Approx. 0.6 L/kg.

Metabolism The drug is metabolized through liver demethylation and conjugation.

Excretion Mainly excreted in bile and feces

Half-life 2-3 hours

PHARMACODYNAMICS

Duration 10-24 hours

Onset Within 2 hours

Peak
3-4 hours after oral administration
Effects

Mechanism The inhibition of the postsynaptic alpha-1 adrenoceptors brought by the drug yields the narrowing effect or
of Action vasoconstriction of catecholamines on the vessels, leading to peripheral blood vessel dilation.
 Minipress is shown to be excreted in small amounts of human milk, and should therefore be taken with caution, especially
OTHERS
by nursing or lactating women.
 Gastrointestinal: vomiting, diarrhea, constipation.
 Cardiovascular: edema, orthostatic hypotension, dyspnea, syncope.
 Central Nervous System: vertigo, depression, nervousness.
 Dermatologic: rash.
 Genitourinary: urinary frequency.
 EENT: blurred vision, reddened sclera, epistaxis, dry mouth, nasal congestion.
 In addition, fewer than 1% of patients have reported the following (in some instances, exact causal relationships
ADVERSE have not been established):
EFFECTS  Gastrointestinal: abdominal discomfort and/or pain, liver function abnormalities, pancreatitis.
 Cardiovascular: tachycardia.
 Central Nervous System: paresthesia, hallucinations.
 Dermatologic: pruritus, alopecia, lichen planus.
 Genitourinary: incontinence, impotence, priapism.
 EENT: tinnitus.
 Other: diaphoresis, fever, positive ANA titer, arthralgia.

CLINICALLY The drug’s dosage should be reduced to 1-2 mg TID and re-titrated if it is meant to be taken with a diuretic or other
IMPORTANT antihypertensive agents. Concomitant administration of the said drug with a PDE-5 inhibitor can result in additive blood
DRUG-DRUG pressure lowering effects and symptomatic hypotension – and should therefore be initiated at the lowest dose possible
INTERACTIONS when taken with Minipress.

CLONIDINE (CATAPRES)
ALPHA 2

GENERIC NAME clonidine

TRADE NAME Catapres

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INDICATIONS Treatment of hypertension alone or in combination with other medications.
Clonidine is available in tablets and transdermal preparation that provides a 7-day duration of action
For oral administration:
DOSAGE &  Adults/Elderly: Initially: 0.1 mg – 0.8 mg b.i.d. or t.i.d. and maximum dosage is 2.4 mg/d
FORMS For topical administration:
 Adults/Elderly: Transdermal patch: 0.1 mg/24 h q7d

PHARMACOKINETICS

Absorption  Well-absorbed in the GI Tract

 Transdermal patch is best absorbed from chest and upper arm and is least absorbed from thigh.
Distribution Protein-binding is 20%-40%

Metabolism Liver

Excretion Urine

Half-life 6-20 hours

 PHARMACODYNAMICS

Duration 6-10 hours

Onset 0.5-1 hour

Peak
2-4 hours
Effects

Clonidine stimulates the alpha2-adrenergic receptors and imidazoline receptor agonists in the brainstem, reducing
Mechanism
sympathetic outflow from the CNS, resulting in vasodilation and decreased blood pressure, thus decreasing peripheral
of Action
resistance, increased blood flow to the kidneys, and decreased afterload.

OTHERS Under pregnancy category C

ADVERSE
Sedation, dry mouth, heart block, rebound hypertension, contact dermatitis with patch, bradycardia, drowsiness
EFFECTS

CLINICALLY
 CNS depressants (e.g., alcohol, morphine, oxyCODONE, zolpidem) - may increase CNS depression.
IMPORTANT  Beta blockers (e.g., atenolol, carvedilol, metoprolol) - ay increase AV blocking effect.
DRUG-DRUG  Tricyclic antidepressants (e.g., amitriptyline, doxepin, nortriptyline) - may decrease effect and may require
INTERACTIONS increased dose of clonidine.
 Digoxin, diltiazem, metoprolol, verapamil - may increase risk of serious bradycardia

sinoatrial (SA) node and are conveyed via a specialized

ANTIDYSRHYTHMIC AGENTS
conducting system to activate all sections of the heart
muscle almost simultaneously.
 This feature allows the heart to continue to beat as long as
ANTIDYSRHYTHMIC AGENTS it has enough nutrition and oxygen to survive, regardless of
 These are a group of drugs that are used to suppress the rest of the body's condition.
abnormal rhythms of the heart, such as atrial fibrillation,
atrial flutter, ventricular tachycardia, and ventricular AUTOMATICITY
fibrillation.  All cardiac cells have some degree of automaticity, in which
they depolarize spontaneously during diastole or rest as the
PHYSIOLOGY flow of potassium ions out of the cell decreases and sodium
CARDIAC OUTPUT leaks into the cell, resulting in an action potential.
 volume of blood pumped by the heart per minute; it is also  The cardiac muscle cell's action potential is divided into five
the method by which blood circulates throughout the body, phases:
particularly to the brain and other essential organs o Phase 0: occurs when the cell reaches a point of
 When the body's demand for oxygen changes, such as stimulation.
during exercise, both heart rate (HR) and stroke volume are  Sodium gates open along the cell
modulated to adjust the cardiac output (SV). membrane, and sodium rushes into the
o As a result, a complicated mechanism combining cell; this positive flow of electrons into the
the autonomic nervous system, endocrine, and cell results in an electrical potential
paracrine signaling pathways regulates cardiac (depolarization).
output. o Phase 1: is a very short period during which the
 Changes in cardiac output compared to baseline are sodium ion concentration equalizes inside and
proportional to changes in total body oxygen requirements. outside of the cell.
Cardiac output will rise during periods of physiologic stress o Phase 2: or the plateau stage, occurs as the cell
to provide appropriate tissue perfusion. membrane becomes less permeable to sodium.
 The product of heart rate (HR) and stroke volume (SV) is  Calcium slowly enters the cell, and
cardiac output, which is measured in liters per minute. The potassium begins to leave the cell. The
number of times the heart beats in one minute is the cell membrane is trying to return to its
most popular definition of HR. The volume of blood resting state, a process called
evacuated during ventricular contraction or during each repolarization.
cardiac stroke is referred to as SV. During systole, not all of o Phase 3: is a time of rapid repolarization as the
the blood that fills the heart at the conclusion of diastole sodium gates are closed and potassium flows out
(end-diastolic volume or EDV) can be evacuated. of the cell.
o As a result, the end-systolic volume is the volume o Phase 4: occurs when the cell comes to rest
left in the heart at the end of systole (ESV). As a  The sodium-potassium pump returns the
result, the stroke volume is equal to the EDV- ESV, membrane to its resting membrane
not the end-diastolic volume. Several factors potential, and spontaneous
influence HR and VS at the same time. depolarization begins again.
 Cardiac output in humans ranges from 5-6 L/min at rest to  Each region of the heart has a somewhat varied action
more than 35 L/min during exercise in elite athletes. potential, which reflects the complexity of the cells in that
region. Each part of the heart has a slightly varying rate of
CONDUCTIVITY rhythmicity as a result of these changes in the action
potential.
 Each cycle of cardiac contraction and relaxation is
governed by impulses that arise spontaneously in the
 o The SA node generates roughly 60 to 100  The atria of the heart pulse very quickly
impulses per minute, the AV node about 40 to 50, but at a regular rhythm in atrial flutter.
and the complex ventricular muscle cells about 10 The rapid rate causes atria contractions
to 20. to be feeble.
 The abnormal wiring within the atria
ARRHYTHMIAS causes atrial flutter.
 Changes in the automaticity or conductivity of the cardiac
cells are involved. o Supraventricular tachycardia (SVT)
 Examples:  SVT is defined by an abnormally fast
o Electrolyte imbalances that modify the action heartbeat that originates above the lower
potential chambers of the heart (ventricles).
o Decreased oxygen delivery to cells that alters the  It's caused by a loop of overlapping
action potential signals in the heart caused by defective
o Structural injury that alters the conduction pathway circuitry that's present from birth.
o Acidosis or waste product accumulation that
influences the action potential o Ventricular tachycardia
 Drugs that modify the action potential or cardiac conduction  Ventricular tachycardia is a fast heart
can sometimes cause changes in the heart's automaticity rate caused by aberrant electrical signals
or conductivity. in the heart's lower chambers
(ventricles).
BRADYCARDIA  The ventricles are unable to fill and
contract efficiently enough to pump
 A heart rate that is slower than normal. Adults' hearts beat enough blood to the body due to the fast
between 60 and 100 times per minute while they are at rest. heart rate.
Your heart beats less than 60 times per minute if you have
bradycardia. o Ventricular fibrillation
 It is a dangerous condition in which the heart beats too  Ventricular fibrillation occurs when the
slowly and cannot pump enough oxygen-rich blood to the lower heart chambers (ventricles) quiver
body. You may feel dizzy, very fatigued or weak, and short instead of pumping vital blood to the body
of breath if this happens. Bradycardia can occur without due to rapid, uncontrolled electrical
causing any symptoms or problems. impulses. If the heart is not returned to a
 Slow heartbeats aren't necessarily a cause for concern. normal beat within minutes with an
During sleep, for example, a resting heart rate of 40 to 60 electric shock to the heart, this can be
beats per minute is relatively normal in some people, fatal (defibrillation).
especially healthy young adults and trained athletes.
 If bradycardia is severe, a pacemaker inserted in the heart DRUG CLASSES
may be required to keep the heart beating at a normal CLASS I (SODIUM CHANNEL BLOCKERS)
rhythm.
 During an action potential, medicines in the class I
TACHYCARDIA antiarrhythmics block sodium channels in the cell
membrane.
 A heart rate of more than 100 beats per minute is known as
tachycardia. Tachycardia can be caused by a variety of THERAPEUTIC ACTION
heart rhythm problems (arrhythmias).
 It's common to have a quick heartbeat from time to time. It's  By binding to sodium channels, class I antiarrhythmics
normal for your heart rate to increase during activity or in stabilize the cell membrane by depressing phase 0 of the
response to stress, trauma, or disease, for example. The action potential and modifying the duration of the action
heart beats quicker than normal in tachycardia due to potential.
o Class Ia medicines lengthen the duration of the
situations unrelated to normal physiological stress.
action potential by suppressing phase 0 of the
 Tachycardia if left untreated, can disturb normal cardiac
action potential.
function and lead to serious problems, such as:
o Class Ib medicines suppress phase 0 and
o Heart failure
actually shorten the action potential's length.
o Stroke
o Class Ic medicines significantly impede
o Sudden cardiac arrest or death
conduction by depressing phase 0, but have
 Tachycardia comes in a variety of forms. They're organized
no influence on the length of the action
by the area of the heart that causes the abnormally fast
potential.
heartbeat and the source of the fast heart rate. The
 Local anesthetics or membrane-stabilizing agents are the
following are examples of tachycardia:
medications in question. They attach more readily to open
o Atrial Fibrillation
or inactive sodium channels—those that have been
 Characterized by a fast heart rate
activated but have not yet repolarized. This property makes
generated by chaotic, irregular electrical
these medications desirable in conditions when the sodium
impulses in the heart's upper chambers
gates are frequently opened, such as tachycardia.
(atria).
 The atria contract rapidly, uncoordinated,
INDICATIONS
and weakly as a response of these
signals.  Because of the possibility of a proarrhythmic impact, these
 Most common type of tachycardia medications should only be used to treat potentially life-
threatening ventricular arrhythmias. They should not be
o Atrial Flutter used to treat other arrhythmias.
 CONTRAINDICATIONS & CAUTIONS DRUGS UNDER CLASS II
 Class I antiarrhythmics are contraindicated in the following  Beta-adrenergic blockers that are used as
situations: allergy to any of these drugs; bradycardia or antidysarrhythmic include: acebutolol (Sectral), esmolol
heart block unless an artificial pacemaker is in place; heart (Brevibloc), and propranolol (Inderal).
failure (HF), hypotension, or shock, which could be  Prototype of this drug class is propranolol.
exacerbated by effects on the action potential; and
electrolyte disturbances, which could alter the effectiveness
of these drugs. CLASS III (POTASSIUM CHANNEL BLOCKERS)
 Patients with renal or hepatic impairment should be  These includes drugs that block cardiac tissue potassium
cautious since these medications' biotransformation and (K+) channels.
excretion may be hampered.
 Although no specific side effects have been linked to the THERAPEUTIC ACTION
use of these drugs during pregnancy, it is recommended
 Blocks potassium channels and slow the outward
that they be taken only if the advantages to the mother
movement of the potassium during the phase 3 of the action
clearly outweigh the potential dangers to the unborn.
potential, which prolongs it.
 Antiarrhythmics of class I penetrate breast milk and should
not be taken during lactation due to the risk of deleterious INDICATIONS
effects on the newborn. A different way to feed the baby
should be chosen.  FDA approved indications for amiodarone are recurrent
ventricular fibrillation (VF) and recurrent hemodynamically
unstable ventricular tachycardia (VT).
DRUGS UNDER CLASS I  They also emphasize that this drug should only be given
when these conditions do not respond to normal therapeutic
 These medications are further classified into three
doses of other antiarrhythmic agents, or if the case of the
subclasses based on how they alter the action potential by
patient is not tolerating the drug that was administered or
blocking sodium channels. The following are examples of
given.
subclasses:
o Class Ia antiarrhythmics: disopyramide
CONTRAINDICATIONS & CAUTIONS
(Norpace), procainamide (Pronestyl), and
quinidine  When their drugs are being used to treat life-threatening
o Class Ib antiarrhythmics: lidocaine (Xylocaine) arrhythmias, it has no contradictions.
and mexiletine (Mexitil)
o Class Ic antiarrhythmics: flecainide (Tambocor) DRUGS UNDER CLASS III
and propafenone (Rythmol)  Potassium channel blockers that are considered as
antidysrhythmics include: amiodarone, dronedarone,
sotalol, ibutilide, dofetilide, and bretylium.
CLASS II (BETA BLOCKERS)  The prototype drug for this class is amiodarone.
 The class II antiarrhythmics are beta-adrenergic blockers
that block beta-receptors, causing a depression of phase
4 of the action potential. CLASS IV (CALCIUM CHANNEL BLOCKERS)
 Class of medications that inhibit voltage-dependent L-type
THERAPEUTIC ACTION calcium channels of cardiac and vascular smooth muscle
 The class II antiarrhythmics competitively block beta- cells.
receptor sites in the heart and kidneys. The result is a
decrease in heart rate, cardiac excitability, and cardiac THERAPEUTIC ACTION
output, a slowing of conduction through the AV node, and a  Blocks the movement of calcium ions across the cell
decrease in the release of renin. membrane, depressing the generation of the action
 These effects stabilize excitable cardiac tissue and potentials and delaying the phases 1 and 2 of
decrease blood pressure, which decreases the heart’s repolarization, which slows automaticity and conduction.
workload and may further stabilize hypoxic cardiac tissue. CONTRAINDICATIONS & CAUTIONS
These drugs are indicated for the treatment of  These types of drugs are contraindicated with any known
supraventricular tachycardia and PVCs. allergy that are related to any calcium channel blockers
which is to avoid possible hypersensitivity reactions.
CONTRAINDICATION & CAUTIONS
 These drugs should not be used if you have sinus DRUGS UNDER CLASS IV
bradycardia (rate less than 45 beats/min) or AV block,  Calcium channel blockers that are used as antidysrhythmic
which could be exacerbated by their effects; if you have include diltiazem and verapamil.
cardiogenic shock, HF, asthma, or respiratory depression,  The prototype drug is diltiazem.
which could worsen due to beta receptor blockage; or if you
are pregnant or lactating because of the risk of harm to the CARDIOTONIC AGENTS
fetus or newborn.
 Affects the intracellular calcium levels in the heart muscle,
 Patients with diabetes and thyroid dysfunction, which could
leading to increased contractility. This increase in
be affected by beta-receptor blockage, and patients with
contraction strength leads to increased cardiac output,
renal and hepatic dysfunction, which could affect the
which causes increased renal blood flow and increased
metabolism and excretion of these medicines, should be
urine production.
cautious.
 Increased renal blood flow decreases renin release,
interfering with the effects of the renin–angiotensin–
aldosterone system, and increases urine output, leading to
 decreased blood volume. The result is a decrease in the heart muscle overstretches from the increased workload,
heart’s workload and relief of HF. and the chambers of the heart dilate secondary to the
 Two types of cardiotonic drugs are used: the classic cardiac increased blood volume that they have had to handle. This
glycosides, which have been used for hundreds of years, hypertrophy (enlargement) of the heart muscle, called
and the newer phosphodiesterase inhibitors. cardiomegaly, leads to inefficient pumping and eventually
to increased HF.
PHYSIOLOGY
HEART FAILURE CELLULAR CHANGES
 Prolonged heart failure causes changes to the myocardial
 Affects the intracellular calcium levels in the heart muscle,
cells. Cells of a failing heart lack the ability of producing the
leading to increased contractility. This increase in
required energy needed for effective contractions.
contraction strength leads to increased cardiac output,
which causes increased renal blood flow and increased
CLINICAL MANIFESTATIONS
urine production.
 Patients with heart failure present a predictable clinical
 Increased renal blood flow decreases renin release,
picture that reflects not only the problems with heart
interfering with the effects of the renin–angiotensin–
pumping, but also with the compensatory mechanisms that
aldosterone system, and increases urine output, leading to
are working to balance the problem.
decreased blood volume. The result is a decrease in the
heart’s workload and relief of HF.  Radiography, electrocardiography (ECG), and direct
o Coronary artery disease (CAD) percussion and palpation helps to detect any changes that
 the leading cause of HF, accounting for are seen in the heart muscle and its function.
approximately 95% of the cases  The heart rate will be a rapid secondary to sympathetic
diagnosed. This is a results of insufficient stimulation, and the patient may develop atrial flutter or
supply of blood to meet the oxygen fibrillation as atrial cells are stretched and damaged.
demands of the myocardium. Examples such as experiencing anxiety often occurs as the
o Cardiomyopathy body stimulates the sympathetic stress reaction. Heart
 is a disease of the heart muscle that murmurs may also develop when the muscle is no longer
leads to an enlarged heart and eventually able to support the papillary muscles that support the valve
to complete muscle failure and death as leaflets or the annuli that anchor the heart valves.
a result of a viral infection, alcoholism,
anabolic steroid abuse, or a collagen LEFT-SIDED HEART FAILURE
disorder. It causes muscle alterations  Reflects engorgement of the pulmonary veins, which will
and ineffective contraction and pumping. eventually lead to difficulty in breathing.
o Hypertension  Patients often complain experiencing tachypnea (rapid,
 It eventually leads to an enlarged cardiac shallow respirations), dyspnea (discomfort with breathing,
muscle because the heart must work often accompanied by a panicked feeling of being unable to
harder than normal to pump against the breathe), and orthopnea (increased difficulty breathing
high pressure in the arteries. when lying down).
o Valvular heart disease o Orthopnea occurs in the supine position when the
 leads to an overload of the ventricles pattern of blood flow changes because of the
because the valves do not close tightly, effects of gravity, which increases pressure and
which allows blood to leak backward into perfusion in the lungs.
the ventricles. This overloading leads to o It is usually relieved when the patient sits up,
muscle stretching and increased demand therefore reducing the blood flow through the
for oxygen and energy as the heart lungs.
muscle must constantly contract harder. o The degree of HF is often calculated by the
 The end result of these conditions is that the heart muscle number of pillows required to get relief (e.g., one-
does not function or cannot pump blood effectively pillow, two-pillow, or three-pillow orthopnea).
throughout the whole vascular system. An example such as  Patients with left-sided HF may also experience coughing
pulmonary edema in which any of the sides of the heart has and hemoptysis (coughing of blood).
a problem in pumping blood, this may lead to heart failures.  In severe cases, the patient may develop pulmonary
edema, which is life-threatening as spaces in the lungs may
COMPENSATORY MECHANISMS fill up with fluid as there are no place for gas exchange to
 The body has several compensatory mechanisms that occur.
function if the heart muscle begins to fail.
 Decreased cardiac output stimulates the baroreceptors in RIGHT-SIDED HEART FAILURE
the aortic arch and the carotid arteries, causing a  Right-sided HF occurs as a result of chronic obstructive
sympathetic stimulation in which this sympathetic pulmonary disease (COPD) or any other lung-related
stimulation causes an increase in heart rate, blood diseases that concerns in the elevation of pulmonary
pressure, and rate and depth of respirations, as well as a pressure.
positive inotropic effect (increased force of contraction) on  This results when the right side of the heart must generate
the heart and an increase in blood volume (through the more and more force to move the blood into the lungs. This
release of aldosterone). commonly occurs with aging, when the venous system fails
 The decrease in cardiac output also stimulates the release to deliver blood to the heart effectively and the hydrostatic
of renin from the kidneys and activates the renin– pressure in the venous end of the capillary increases, which
angiotensin–aldosterone system, which further increases leads to a loss of fluid in the tissues and changes in the
blood pressure and blood volume. overall efficiency of the vascular system.
 Over time, these effects increase the workload of the heart,  In the right-side of the HF, venous return to the heart is
contributing to further development of HF. Eventually, the decreased due to the increased pressure in the right side of
 the heart in which it causes congestion and backup of blood o electrolyte abnormalities, which could alter the
in the systemic system. action potential and change the effects of the drug.
 Jugular venous pressure (JVP) rises and it can be observed  Digoxin should be used cautiously in patients who are
in distended neck veins reflecting increased central venous pregnant or lactating because of the potential for adverse
pressure (CVP). effects on the fetus or neonate. It is not known whether
o Liver enlarges and becomes congested with digoxin causes fetal toxicity though we should take note that
blood, which initially leads to pain and tenderness it should be given during pregnancy only if the benefit to the
and eventually to liver dysfunction and jaundice. mother clearly outweighs the risk to the fetus.
 Dependent areas may develop edema or swelling of the  The drug does enter breast milk, but it has not been shown
tissues as fluid leaves the congested blood vessels and to cause problems for the neonate. Caution should be used,
pools into the tissues. Pitting edema in the legs is a however, during lactation. Pediatric and geriatric patients
common finding, as it reflects fluid pooling in the tissues. also are at higher risk.
When the patient with right-sided HF changes position and
the legs are no longer dependent, the fluid moves back into
circulation to be returned to the heart. The increase in PHOSPHODIESTERASE INHIBITOR
cardiovascular volume increases blood flow to the kidneys,  Belongs to a second class of drugs that act as cardiotonic
causing increased urine output. agents.This includes inamrinone and milrinone.
o This is often seen as nocturia (excessive voiding
during the night), when a person is awake at day THERAPEUTIC ACTION
and being in a supine position at night. The patient
 The phosphodiesterase inhibitors block the enzyme
may need to get up during the night to excrete all
phosphodiesterase. This blocking effect leads to an
of the urine that has been produced during the
increase in myocardial cell cyclic adenosine
fluid shift.
monophosphate (cAMP), which increases calcium levels in
the cell.
CARDIAC GLYCOSIDES  Increased in cellular calcium causes a stronger contraction
and prolongs the effects of sympathetic stimulation, which
 Used to be derived from the fox-glove or digitalis plant. can lead to vasodilation, increased oxygen consumption,
 Digoxin (Lanoxin) is the drug often used to treat HF. and arrhythmias. These drugs are indicated for the short-
term treatment of HF that has not responded to digoxin or
diuretics alone or that has had a poor response to digoxin,
THERAPEUTIC ACTION diuretics, and vasodilators.
 Digoxin increases intracellular calcium and allows more
calcium to enter the myocardial cells during depolarization CONTRAINDICATIONS & CAUTIONS
which causes the following effects:  Phosphodiesterase inhibitors are contraindicated in the
o Increased force of myocardial contraction. presence of allergy to either of these drugs or to bisulfites.
o Increased cardiac output and renal perfusion.  They also are contraindicated in the following conditions
o Slowed heart rate, owing to slowing of the rate of such as severe aortic or pulmonic valvular disease, which
cellular repolarization. could be exacerbated by increased contraction; acute MI,
o Decreased conduction velocity through the which could be exacerbated by increased oxygen
atrioventricular node. The overall effect is a consumption and increased force of contraction; fluid
decrease in the myocardial workload and relief of volume deficit, which could be made worse by increased
HF. renal perfusion; and ventricular arrhythmias, which could be
exacerbated by these drugs.
INDICATION  Caution should be used in the elderly, as they are more
 Digoxin is indicated for the treatment of HF, atrial flutter, prone to adverse effects of the drug.
atrial fibrillation, and paroxysmal atrial tachycardia.  There are no adequate studies about the effects of these
 Digoxin has a very narrow margin of safety, so extreme care drugs during pregnancy. It is not yet known whether these
must be taken when using this drug. drugs enter breast milk, so precautions should be used if a
patient is breast-feeding.
CONTRAINDICATIONS & CAUTIONS
 Cardiac glycosides are contraindicated in the presence of
allergy to any component of the digitalis preparation. OTHER ANTIDYSRHYTHMIC AGENTS
 Digoxin is contraindicated in the following conditions: MAGNESIUM SULFATE.
o Ventricular tachycardia or fibrillation, which are THERAPEUTIC ACTION
potentially fatal arrhythmias and should be treated
with other drugs.  Magnesium is the second most plentiful cation of the
o heart block or sick sinus syndrome, which intracellular fluids, and it is essential for the activity of many
could be made worse by slowing of conduction enzyme systems and plays an important role in
through the atrioventricular node neurochemical transmission and muscular excitability.
o idiopathic hypertrophic sub-aortic stenosis  It also reduces striated muscle contractions and blocks
(IHSS), which the increase in force of contraction peripheral neuromuscular transmission by reducing
could obstruct the outflow tract to the aorta and acetylcholine release at the myoneural junction.
cause severe problems
o acute MI, because the increase in force of INDICATION
contraction could cause more muscle damage and  It is used to treat convulsions during pregnancy, nephritis in
infarct children, magnesium deficiency, and tetany.
o renal insufficiency, because the drug is excreted
through the kidneys and toxic levels could develop
 CONTRAINDICATIONS & CAUTIONS  Evaluate the skin for any changes such as in coloration,
 Cardiac disease in the form of myocardial damage is lesions that are currently present, and temperature to detect
generally considered a contraindication of magnesium adverse reactions and to assess cardiac output.
salts; however, magnesium sulfate has been used in acute  Obtain a baseline ECG to evaluate heart rate and rhythm,
myocardial infarction patients to reduce reperfusion injury, monitor the results of laboratory tests which includes
decrease infarct size, and to prevent arrhythmias. complete blood count. This is to identify if there are possible
 Magnesium salts should also be used with caution in bone marrow suppression, and renal and liver function
patients with electrolyte imbalance. In addition, do not use tests, which is to determine if there is any need for possible
magnesium salts in patients with preexisting changes in the dose and identify any toxic effects.
hypermagnesemia.
DIAGNOSIS
 Decreased cardiac output related to cardiac effects of the
ADENOSINE drug
THERAPEUTIC ACTION  Ineffective tissue perfusion related to decreased blood flow
 The agonism of adenosine receptors A1 and A2 reduces to different parts of the body
conduction time in the atrioventricular node of the heart.  Altered sensory perception related to CNS drug effects
 Conduction time is decreased by inducing potassium efflux  Higher risk of injury related to weakness and dizziness
and inhibiting calcium influx through channels in nerve cells,
which leads to hyperpolarization and the increased IMPLEMENTATION
threshold for calcium dependent action potentials.  Titrate the dose to the smallest amount that is manageable
 The decreased conduction time leads to an antiarrhythmic enough for arrhythmia to decrease the risk of drug toxicity.
effect. Inhibition of calcium influx reduces the activity of  Monitor cardiac rhythm closely to detect potential serious
adenylate cyclase, relaxing vascular smooth muscle. The adverse effects and to evaluate the drug effectiveness.
then relaxed vascular smooth muscle leads to increased  Provide comfort and safety measures such as raising side
blood flow through normal coronary arteries but not stenotic rails, adequate room lighting, noise control. This will help
arteries, allowing thallium-201 to be more readily up taken the patient to tolerate drug effects.
in normal coronary arteries.  Ensure readiness such as maintenance of emergency
drugs and equipment at bedside to promote prompt
INDICATION treatment in case of severe toxicity.
 Medication used in myocardial perfusion scintigraphy and  Educate the patient on drug therapy including the drug
to treat supraventricular tachycardia. name, its indication, and adverse effects to watch out for to
promote proper drug awareness to the patient and proper
understanding of drug therapy and thereby promote
CONTRAINDICATIONS & CAUTIONS adherence to drug regimen.
 Adenosine is contraindicated in patients with known
adenosine hypersensitivity. Dyspnea, throat tightness, EVALUATION
flushing, erythema, rash, and chest discomfort have  Closely monitor the patient for any response to the drug
occurred after adenosine administration. such as the stabilization of cardiac rhythm and output.
 Symptomatic treatment may be required. Have medical  Monitor for any adverse effects that will show such as
personnel ready and appropriate treatment available. sedation, respiratory depression, and CNS effects.
Resuscitative measures may be necessary if symptoms  Evaluate patient understanding about drug therapy by
progress asking questions related to the drug itself such as the name
of the drug, its indication, and any adverse effect that they
should watch out for.
 Monitor patient compliance to drug therapy.
NURSING CONSIDERATIONS
ASSESSMENT
 When receiving antiarrhythmic drugs, they should assess
for any contradictions or cautions such as allergies to these
types of drugs, impaired liver or kidney function, conditions
that could be exacerbated by the depressive effects of the
drugs, and lactation for pregnant women.
 Perform physical assessment and assess the patient’s
neurological statues, which includes their level of alertness,
speech and vision, and their reflexes.
 Assess the patient’s cardiac status closely such as their
pulse, blood, pressure, heart rate, rhythm, auscultate heart
sounds, and noting any evidence of abnormal sounds.
 Anticipate cardiac monitoring and evaluate any heart rate
and rhythm and aid in identifying arrhythmia.
 Closely monitor the respiratory rate and depth and
auscultate the lungs for any evidence of adventitious
sounds to identify respiratory depression and detect
changes associated with heart failure.
 Inspect abdomen for evidence of distention; auscultate
bowel sounds to evaluate GI motility.
 ANTIDYSRHYTHMIC AGENTS

LIDOCAINE
CLASS I – SODIUM CHANNEL BLOCKERS

GENERIC Lidocaine
NAME

TRADE NAME Dilocaine, Solarcaine, Xylocaine, Lidoderm, Octocaine

IMAGE

Image from: https://dailymed.nlm.nih.gov/dailymed/image.cfm?name=51662-1505-

1+50+mL+Serialized+Vial+Labeling.jpg&id=457374

INDICATIONS Lidocaine is an anesthetic of the amide group indicated for production of local or regional anesthesia by infiltration techniques
such as percutaneous injection and intravenous regional anesthesia by peripheral nerve block techniques such as brachial
plexus and intercostal and by central neural techniques such as lumbar and caudal epidural blocks.

DOSAGE & Lidocaine is available in infusion solution, injectable solutions, and for topical administration.
FORMS
For ventricular arrhythmias or ventricular tachycardia:
 1-1.5 mg/kg slow IV bolus over 2-3 minutes
 May repeat doses of 0.5-0.75 mg/kg in 5-10 minutes up to 3 mg/kg total if refractory VF or pulseless VT
 Continuous infusion: 1-4 mg/min IV after return of perfusion
 Administer 0.5 mg/kg bolus and reassess infusion if arrhythmia reappears during constant infusion
 If IV not feasible may use IO/ET
 Endotracheal (loading dose): 2-3.75 mg/kg (2 to 2.5 recommended IV dose); dilute in 5-10 mL 0.9% saline or sterile
water

PHARMACOKINETICS

Absorption In general, lidocaine is readily absorbed across mucous membranes and damaged skin but poorly through intact skin. The
agent is quickly absorbed from the upper airway, tracheobronchial tree, and alveoli into the bloodstream.

Distribution The volume of distribution determined for lidocaine is 0.7 to 1.5 L/kg

Metabolism Lidocaine is metabolized predominantly and rapidly by the liver, and metabolites and unchanged drug are excreted by the
kidneys

Excretion Urine

Half-life 1-2 hours

PHARMACODYNAMICS

Duration IM: 2 h
IV: 10–20 min
 Onset IM: 5–10 min
IV: Immediate

Peak Effects IM: 5–15 min

IV: Immediate

Mechanism  Lidocaine is a local anesthetic of the amide type. It is used to provide local anesthesia by nerve blockade at various
of Action sites in the body. It does so by stabilizing the neuronal membrane by inhibiting the ionic fluxes required for the
initiation and conduction of impulses, thereby affecting local anesthetic action.
 In particular, the lidocaine agent acts on sodium ion channels located on the internal surface of nerve cell
membranes. At these channels, neutral uncharged lidocaine molecules diffuse through neural sheaths into the
axoplasm where they are subsequently ionized by joining with hydrogen ions. The resultant lidocaine cations are
then capable of reversibly binding the sodium channels from the inside, keeping them locked in an open state that
prevents nerve depolarization.
 As a result, with sufficient blockage, the membrane of the postsynaptic neuron will ultimately not depolarize and
will thus fail to transmit an action potential. This facilitates an anesthetic effect by not merely preventing pain signals
from propagating to the brain but by aborting their generation in the first place

OTHERS Intravenous lidocaine infusions are also used to treat chronic pain and acute surgical pain as an opiate sparing technique.
The quality of evidence for this use is poor so it is difficult to compare it to placebo or an epidura

ADVERSE Dizziness, light-headedness, fatigue, arrhythmias, cardiac arrest, nausea, vomiting, anaphylactoid reactions, hypotension,
EFFECTS vasodilation.

CLINICALLY  The risk for arrhythmia increases if these agents are combined with other drugs that are known to cause
IMPORTANT arrhythmias, such as digoxin and the beta-blockers.
DRUG-DRUG  The risk of bleeding effects of these drugs increases if they are combined with oral anticoagulants; patients
INTERACTION receiving this combination should be monitored closely and have their anticoagulant dose reduced as needed.
S  Check individual drug monographs for specific interactions associated with each drug.

PROPANOLOL
CLASS II – BETA BLOCKERS

GENERIC Propanolol
NAME

TRADE NAME Inderal

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988.jpg

INDICATIONS Treatment of supraventricular tachycardia caused by digoxin or catecholamine in adults; also used as an antihypertensive,
antianginal, and anti-migraine headache drug.

DOSAGE & For hypertension:

FORMS
 Immediate release: 40 mg PO q12hr initially, increasing every 3-7 days; maintenance: 80-240 mg PO q8-12hr; not
to exceed 640 mg/day
 Inderal LA: 80 mg/day PO initially; maintenance: 120-160 mg/day; not to exceed 640 mg/day
 For supraventricular arrhythmia:
 PO: 10-30 mg q6-8hr
 IV: 1-3 mg at 1 mg/min initially; repeat q2-5min to total of 5 mg
 Once response or maximum dose achieved, do not give additional dose for at least 4 hours

PHARMACOKINETICS

Absorption Completely absorbed.

Distribution Approximately 4L/kg or 320L.

Metabolism Extensively metabolized with most metabolites appearing in the urine

Excretion Urine

Half-life 8 hours

PHARMACODYNAMICS

Duration Oral: 6–12 h

IV: 4–6 h

Onset Oral: 20–30 min

IV: Immediate

Peak Effects Oral: 60–90 min

IV: 1 min

Mechanism Propranolol undergoes side chain oxidation to α-naphthoxylactic acid, ring oxidation to 4’-hydroxypropranolol, or
of Action glucuronidation to propranolol glucuronide. It can also be N-desisopropylated to become N-desisopropyl propranolol. 17%
of a dose undergoes glucuronidation and 42% undergoes ring oxidation

ADVERSE The adverse effects associated with class II antiarrhythmics are related to the effects of blocking beta-receptors in the
EFFECTS sympathetic nervous system. CNS effects include dizziness, insomnia, dreams, and fatigue. Cardiovascular symptoms can
include hypotension, bradycardia, AV block, arrhythmias, and alterations in peripheral perfusion. Respiratory effects can
include bronchospasm and dyspnea. GI problems frequently include nausea, vomiting, anorexia, constipation, and diarrhea.
Other effects to anticipate include a loss of libido, decreased exercise tolerance, and alterations in blood glucose levels.

CLINICALLY The risk of adverse effects increases if these drugs are taken with verapamil; if this combination is used, dose adjustment
IMPORTANT will be needed. There is a possibility of increased hypoglycemia if these drugs are combined with insulin; patients should be
DRUG-DRUG monitored closely. Other specific drug interactions may occur with each drug; check a drug reference before combining
INTERACTION these drugs with any others.
S

AMIODARONE
CLASS III – POTASSIUM CHANNEL BLOCKERS

GENERIC Amiodarone
NAME

TRADE NAME Pacerone

IMAGE

Image from: https://www.drugs.com/pro/pacerone.html

INDICATIONS This drug should only be given when these conditions do not respond to normal therapeutic doses of other antiarrhythmic
agents, or if the case of the patient not tolerating the drug that was administered or given.

DOSAGE & Dosage should be given based on the severity of arrhythmia and the response. Must use the lowest effective dosage.
FORMS Recommended dosage should start on the initial treatment with a loading dose of 800 to 1600 mg/day until the initial
therapeutic response occurs at around 1 to 3 weeks. If side effects becomes prominent, reduce Pacerone doses to 600 to
800 mg/day for one month. Maintenance dose are usually 400 mg/day.
Dosage forms are 400 mg tablets which are light yellow, oval-shaped, scored, uncoated tablets, which are debossed with
“P400” on the unscored side, and “01” to the left and “45” to the right of the score on the reverse side

PHARMACOKINETICS

Absorption The Cmax of amiodarone in the plasma is achieved about 3 – 7 hours after its administration.

Distribution Distributed in the decreasing order from the lung, live, thyroid gland, kidney, heart, adipose tissue, muscle tissue and brain.

Metabolism Main metabolite is desethylamiodarone or DEA by the enzymes CYP3A4 and CYP2C8. The enzyme is found in the liver
and intestines.

Excretion Urine

Half-life 10 days

PHARMACODYNAMICS

Duration 6-8 hours

Onset 2 – 3 days

Peak Effects 3-7 hours after administration

Mechanism Blocks cardiac K channels to prolong repolarization

of Action

OTHERS Used to help keep the heart beating normally in people with life threatening hearth rhythm disorders of the ventricles.

ADVERSE Hypersensitivity pneumonitis, interstitial pneumonitis, pulmonary toxicity, blurred vision, peripheral neuropathy, phototoxicity,
EFFECTS and visual halos around lights.

CLINICALLY These drugs can cause serious toxic effects if they are combined with digoxin or quinidine. There is an increased risk of
IMPORTANT proarrhythmias if they are combined with antihistamines, phenothiazines, or tricyclic antidepressants. There is an increased
DRUG-DRUG risk of serious adverse effects if dofetilide is combined with ketoconazole, cimetidine, or verapamil, and so these
INTERACTION combinations should be avoided. Sotalol may have a loss of effectiveness if it is combined with nonsteroidal antiinflammatory
S drugs, aspirin, or antacids

DILTIAZEM
CLASS IV – CALCIUM CHANNEL BLOCKERS

GENERIC Diltiazem
NAME

TRADE NAME Cardizem

IMAGE

Image from: https://www.mdsupplies.com/medical-supplies-Cardizem-DILTIAZEM-Diltiazem-HCL-5mgmL-25-mL-

IZESBY8PSC.html
INDICATIONS  Oral: Management of hypertension, lowering of blood pressure, alone or can be combined with other hypertensive
agents.
 Intravenous: Short-term management of atrial fibrillation or atrial flutter for the temporary control of rapid
ventricular rate.
 Off-label: Uses in anal fissures, migraine prophylaxis, cramps in lower leg related to rest, pulmonary hypertension,
idiopathic dilated cardiomyopathy, and proteinuria associated with diabetic nephropathy.

DOSAGE &  Must be adjusted in accordance with the patient’s needs. Starting dosage would be 30 mg four times daily, in before
FORMS meals and bedtime, and dosage should be increased gradually at 1-to-2-day intervals until optimum response is
obtained.
 30 mg – CARDIZEM tablets may be swallowed whole, crushed, or chewed. Do not split CARDIZEM tablets.
 60 mg, 90 mg, and 120 mg – CARDIZEM tablets may be swallowed whole, crushed, or chewed.

PHARMACOKINETICS

Absorption Readily absorbed in the gastrointestinal tract.

Distribution The apparent volume of distribution of diltiazem was approximately 305 L following a single intravenous injection

Metabolism Metabolized in the liver.

Excretion Urine

Half-life 3.5 – 6 hours

PHARMACODYNAMICS

Duration 6 – 8 hours

Onset 30 – 60 minutes

Peak Effects 2 -3 hours

Mechanism Blocks the movement of calcium ions across the cell membrane, depressing the generation of action potentials, delaying
of Action phases 1 and 2 of repolarization, and slowing conduction through the AV node.

OTHERS Class IV antiarrhythmics are calcium channel blockers that shorten the action potential, disrupting ineffective rhythms and
rates

ADVERSE Dizziness, light-headedness, headache, asthenia, peripheral edema, bradycardia, AV block, flushing, nausea, hepatic injury.
EFFECTS

CLINICALLY Potentially serious effects to keep in mind include increased serum levels and toxicity of cyclosporine ifthey are taken with
IMPORTANT diltiazem and increased risk of heart block and digoxin toxicity if they are combined with verapamil (because verapamil
DRUG-DRUG increases digoxin serum levels). Both verapamil and digoxin depress myocardial conduction. If any combinations of these
INTERACTION drugs must be used, the patient should be monitored very closely and appropriate dose adjustments made. Verapamil has
S also been associated with serious respiratory depression when given with general anesthetics or as an adjunct to anesthesia.

DIGOXIN
CARDIAC GLYCOSIDES

GENERIC Digoxin
NAME

TRADE NAME Digitek, Digox, Lanoxin, Toloxin

IMAGE

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INDICATIONS Treatment of HF, atrial flutter, atrial fibrillation, and paroxysmal atrial tachycardia

DOSAGE & Digoxin is available in tablet form, oral solution, and injectable solution.
FORMS
For emergency treatment of heart failure (IV):
 Adult: For patients who have not received cardiac glycosides in the previous 2 weeks. Dosage is individualised
according to age, lean body weight and renal status. Loading dose of 500-1,000 mcg (0.5-1 mg) by IV infusion over
a period of 10-20 minutes in divided doses with approx half of the dose given as first dose and further fractions of
the total dose given every 4-8 hours.
 Child: Loading dose: Preterm neonates <1.5 kg: 25 mcg/kg/day; 1.5-2.5 kg: 30 mcg/kg/day. Term neonates-2
years 45 mcg/kg/day; >2-5 years 35 mcg/kg/day; >5-10 years 25 mcg/kg/day. Maintenance: Preterm neonates
20% of 24-hour loading dose; Term neonates and children up to 10 years 25% of 24-hour loading dose.
 Elderly: Dosage reductions may be needed.
For heart failure and supraventricular arrhythmias:
 Adult: Dosage is individualised according to age, lean body weight and renal status. Rapid digitalisation: Loading
dose of 750-1,500 mcg (0.75-1.5 mg) during the first 24-hour period as a single dose; or in divided doses every 6
hours for less urgent or greater risk cases. For mild heart failure (loading dose may not be required): 250-750 mcg
(0.25-0.75 mg) daily for 1 week. Maintenance: Individualised based on the percentage of the peak body stores lost
each day. Usual maintenance: 125-250 mcg daily but may range from 62.5-500 mcg daily.
 Child: Loading dose: Preterm neonates <1.5 kg: 25 mcg/kg/day; 1.5-2.5 kg: 30 mcg/kg/day. Term neonates to 2
years 45 mcg/kg/day; >2-5 years 35 mcg/kg/day; >5-10 years 25 mcg/kg/day. Loading dose is given in divided
doses with approx half the total dose given as the 1st dose and further fractions of the total dose given at intervals
of 4-8 hours. Maintenance: Preterm neonates 20% of 24-hour loading dose; Term neonates and children up to 10
years 25% of 24-hour loading dose.
 Elderly: Dosage reductions may be needed.

PHARMACOKINETICS

Absorption Approximately 70-80% absorbed in the first part of the small bowel

Distribution Distributed in the skeletal muscle followed by the heart and kidneys

Metabolism Several urinary metabolites of digoxin exist, including dihydrodigoxin and digoxigenin bisdigitoxoside

Excretion Urine

Half-life 30-40 hours

PHARMACODYNAMICS

Duration 6-8 days

Onset 30-120 minutes

Peak Effects 2-6 hours

Mechanism Increases intracellular calcium and allows more calcium to enter the myocardial cell during depolarization; this causes a
of Action positive inotropic effect which is an increased force of contraction, increased renal perfusion with a diuretic effect and
decrease in renin release, a negative chronotropic effect which is a slower heart rate, and slowed conduction through the
atrioventricular (AV) node.

OTHERS Also used to treat atrial fibrillation, a heart rhythm disorder of the atria, which is the upper chambers of the heart that allow
blood to flow into the heart.

ADVERSE Headache, weakness, drowsiness, visual disturbances, arrhythmias, GI upset

EFFECTS

CLINICALLY There is a risk of increased therapeutic effects and toxic effects of digoxin if it is taken with verapamil, amiodarone, quinidine,
IMPORTANT quinine, erythromycin, tetracycline, or cyclosporine. If digoxin is combined with any of these drugs, it may be necessary to
DRUG-DRUG decrease the digoxin dose to prevent toxicity. If one of these drugs has been part of a medical regimen with digoxin and is
INTERACTION discontinued, the digoxin dose may need to be increased. The risk of cardiac arrhythmias could increase if these drugs are
S taken with potassium-losing diuretics. If this combination is used, the patient’s potassium levels should be checked regularly
and appropriate replacement done. Digoxin may be less effective if it is combined with thyroid hormones, metoclopramide,
or penicillamine, and increased digoxin dose may be needed. Absorption of oral digoxin may be decreased if it is taken with
cholestyramine, charcoal, colestipol, antacids, bleomycin, cyclophosphamide, or methotrexate. If it is used in combination
with any of these agents, the drugs should not be taken at the same time but should be administered 2 to 4 hours apart.
 INAMRINONE
PHOSPHODIESTERASE INHIBITORS

GENERIC Inamrinone
NAME

TRADE NAME Inocor

IMAGE

Image from https://www.drugs.com/pro/inamrinone.html

INDICATIONS Used in the treatment of congestive heart failure.

DOSAGE &  For congestive heart failure: Load: 0.75 mg/kg IV bolus over 2-3 minutes, then 5-10 mcg/kg/min IV. Total daily
FORMS dose (including loading dose) should not exceed 10 mg/kg/day. Therapeutic dosage range: 0.5-7 mcg/mL
 For renal impairment: CrCl <10 mL/min: Administer 50-75% of the dose. CrCl ≥10 mL/min: Dosage adjustment not
required.

PHARMACOKINETICS

Absorption Not available.

Distribution 1.2 L/kg

Metabolism Liver

Excretion Urine and Feces

Half-life 3.6 hours to 5.8 hours

PHARMACODYNAMICS

Duration 2 hours

Onset Immediate

Peak Effects 10 minutes

Mechanism Blocks the enzyme phosphodiesterase, which leads to an increase in myocardial cell cAMP, which increases calcium levels
of Action in the cell, causing a stronger contraction and prolonged response to sympathetic stimulation; directly relaxes vascular
smooth muscle

OTHERS The drug should be used only in patients who can be closely monitored and who have not responded adequately to digitalis,
diuretics, and/or vasodilators.

ADVERSE Arrhythmias, hypotension, nausea, vomiting, thrombocytopenia, pericarditis, pleuritis, fever, chest pain, burning at injection
EFFECTS site.

CLINICALLY Precipitates form when these drugs are given in solution with furosemide. Avoid this combination in solution. Use alternate
IMPORTANT lines if both of these drugs are being given intravenously.
DRUG-DRUG
INTERACTION
S
 OTHER ANTIDYSRHYTHMIC AGENTS

MAGNESIUM SULFATE

GENERIC Magnesium sulfate

NAME

TRADE NAME Concept OB

IMAGE

Image from: https://www.drugs.com/pro/concept-ob-capsules.html

INDICATIONS This is used for immediate control of life-threatening convulsions in the treatment of severe toxemias (pre-eclampsia and
eclampsia) of pregnancy and in the treatment of acute nephritis in children.

DOSAGE & For severe pre-eclampsia or eclampsia:

FORMS
 Initial dose: 4 to 5 grams IV in 250 mL of appropriate diluent, with simultaneous IM administration of up to 5 grams
(10 mL undiluted solution) in EACH buttock; total dose: 10 to 14 grams
 Initial IV dose of 4 grams may also be diluted to a 10% or 20% solution and injected IV over 3 to 4 minutes
 Maintenance dose: 4 to 5 grams IM into alternate buttocks every 4 hours as needed or maintenance dose: 1 to 2
grams/hour IV by constant infusion.
 Maximum dose: 30-40 g/day

PHARMACOKINETICS

Absorption Slow and poor

Distribution Bone (50% to 60%); extracellular fluid (1% to 2%)

Metabolism Not available

Excretion Urine and Feces

Half-life 43.2 hours (newborns)

PHARMACODYNAMICS

Duration Anticonvulsant activity: IM: 3 to 4 hours; IV: 30 minutes

Onset Anticonvulsant: IM: 1 hour; Anticonvulsant: IV: Immediate; Laxative: Oral: 0.5 to 6 hours

Peak Effects Not available.

Mechanism It reduces striated muscle contractions and blocks peripheral neuromuscular transmission by reducing acetylcholine release
of Action at the myoneural junction

OTHERS It is also being used for pediatric acute nephritis and to prevent seizures in severe pre-eclampsia, eclampsia, or toxemia of
pregnancy.

ADVERSE Circulatory collapse, respiratory paralysis, low core body temperature (hypothermia), excess fluid in the lungs (pulmonary
EFFECTS edema), depressed/poor reflexes, low blood pressure (hypotension)

ADENOSINE

GENERIC Adenosine
NAME

TRADE NAME Adenocard

IMAGE

Image from: https://www.buyemp.com/product/adenosine-adenocard-injection-vials/group000095

INDICATIONS This drug is indicated as an adjunct to thallium-201 in myocardial perfusion scintigraphy in patients that are unable to receive
adequate exercise.

DOSAGE & Injectable solution:

FORMS
 6mg/2mL prefilled syringe
 12mg/4mL prefilled syringe

PHARMACOKINETICS

Absorption Readily absorbed as it is administered through I.V

Distribution It is rapidly taken up by erythrocytes and vascular endothelial cells.

Metabolism  Through blood and tissue

 It is deaminated to inosine and subsequently to hypoxanthine; also undergoes phosphorylation to adenosine
monophosphate (AMP) within blood cells

Excretion Not available

Half-life <10 sec.

PHARMACODYNAMICS

Duration <10 sec.

Onset 20-30 sec.

Peak Effects Immediate

Mechanism Slows conduction through AV node and interrupts AV reentry pathways, which restore normal sinus symptoms
of Action

OTHERS Treatment of supraventricular tachycardias, including (Adenocard) may repeat with 12-mg IV bolus after those caused by
the use of alternate conduction 1–2 min if needed, may be repeated a pathways in adults

ADVERSE chest pain, facial flushing, hypotension, palpitations

EFFECTS
 ANTIANGINAL AGENTS
delivery to the heart muscle fibers through division and
subdivision.
 Antianginals are drugs or chemical agents used primarily to  The heart muscle receives its blood supply during diastole,
restore the balance between the supply and demand ratios while it is at rest.
in oxygen delivery to the myocardium when the rest is not  It is unable to receive blood during systole when the heart
sufficient. muscle contracts and it becomes tight and clamps the blood
 These drugs can also help in improve blood delivery to the vessels shut. It is the same time when all other tissues
heart muscle in two ways: receive fresh blood.
o By dilating blood vessels through increasing  While the heart is at rest, the openings in the sinuses of
supply of oxygen Valsalva are positioned so that they can be filled when the
o By decreasing the workload of the heart so that the blood flows back against the aortic valve.
heart would have less oxygen demand.  Pulse pressure is the pressure that fills the vessels and the
 These drugs are utilized to prevent myocardial cell death pressure of the column of blood falling back onto the closed
when the coronary vessels are currently seriously harmed aortic valve.
and are experiencing difficulty keeping up with the blood
flow to the heart muscle. CORONARY ARTERY DISEASE (CAD)
 The imbalance in the supply and demand ratio in oxygen  Is characterized by progressive narrowing of coronary
delivery to the myocardium is manifested by pain and is arteries which leads to decreased oxygen delivery to
most commonly due to coronary artery diseases (CAD). cardiac muscle cells which is due to the imbalance in the
 All antianginal agents are effective and may be used in supply and demand ratio in oxygen delivery to the
combination to achieve good pain control. The type of drug myocardium and is manifested by pain.
that is best for a patient is determined by tolerance of  It has been the leading cause of death in the United States
adverse effects and response to the drug. and most Western nations.
 Antianginal agents are classified into nitrates, beta-  In coronary artery disease, the lumens of the blood vessels
blockers, calcium channel blockers, and angiotensin- become narrowed due to the development of atheromas or
receptor neprilysin inhibitors. the fatty tumors in the intima of the vessels in a process
called atherosclerosis, where blood is no longer able to flow
PHYSIOLOGY freely to the muscle cells. These deposits cause harm to the
ANGINA intimal lining of the vessels, attracting platelets and immune
 The body’s response to a lack of oxygen in the heart muscle factors and causing the swelling and development of a
is pain. larger deposit.
 Even though the heart muscle does not have any pain  The vessel size is severely decreased because of the
fibers, a substance called factor P is released from ischemic deposits overtime. It is also losing its natural elasticity and
myocardial cells and pain is felt wherever substance P becomes unable to respond to normal stimuli to dilate or
reacts with a pain receptor. constrict to meet the needs of the tissues.
 Stable angina is the condition that occurs when the heart  The heart muscle becomes hypoxic due to inability of
muscle is perfused adequately except during exertion or narrowed vessels to respond to the supply of the blood
increased demand. needed by the heart that normally stimulates the vessels to
 Unstable or preinfarction angina is a condition where the deliver more blood. Thus, having an imbalance between
narrowing of the coronary arteries becomes more oxygen supply and demand manifested by pain.
pronounced so that the heart may experience episodes of
ischemia even when the patient is at rest. The person is still ACUTE MYOCARDIAL INFARCTION
at an increased risk of a complete blockage of blood supply  This occurs when a coronary vessel becomes completely
to the heart muscle if the oxygen demand increases and the blocked and is unable to deliver blood to the cardiac
heart needs to work harder. muscle, the area of muscle that is dependent on the vessel
 Prinzmetal angina is the spasm of a coronary vessel, not for oxygen becomes ischemic and the necrotic. It can heal
just by vessel narrowing, which decreases the flow of blood through scar tissue replacement of the dead cells.
through the narrowed lumen.  The pain can be excruciating, with nausea and severe
sympathetic stress reaction possible.
ANGINA PECTORIS  One of the possible dangers of myocardial infarction is that
 Suffocation of the chest that occurs when the narrowed arrhythmias can develop in nearby tissue that is ischemic
vessels cannot accommodate the myocardial demand for and very irritable. Most of the deaths caused by myocardial
oxygen. infarction occur as a result of fatal arrhythmias.
 It is the pain or discomfort caused when heart muscles do  Within 6 to 10 weeks, scar tissue will form the necrotic area
not receive enough oxygen or the imbalance between and muscle will compensate for the injury only if the heart
oxygen being supplied to the heart muscle and demand for muscle has a chance to heal. However, if the area of the
oxygen by the heart muscle. muscle is severely damaged, the muscle may not be able
to compensate for the loss and heart failure or even
MYOCARDIUM cardiogenic shock may occur.
 It is the muscular middle layer which makes up the bulk of
the heart. It is composed of involuntary, striated, branched DRUG CLASSES
and contracting fibers which allow the heart to contract. NITRATES
 Constant blood supply is needed for the oxygen and THERAPEUTIC ACTION
nutrients to maintain a constant pumping action.  It relaxes and dilates veins, arteries, and capillaries,
 The myocardium receives all of its blood from two coronary allowing increased blood flow through the vessels and
arteries that exit the sinuses of Valsalva at the base of the because of a drop in resistance, it lowers systemic blood
aorta and these vessels form the capillaries for oxygen pressure.
 Nitrates have a very small impact on increasing blood flow  These drugs are sometimes used in therapy with nitrates
through coronary arteries because of CAD causing due to its reduced adverse effects and increased exercise
stiffening and lack of responsiveness in these arteries. But tolerance.
they still increase blood flow through healthy coronary
arteries, helping the heart to compensate. INDICATIONS
 Its main effect is a drop in systemic blood pressure. The  These drugs are not indicated for the treatment of
vasodilation causes blood to pool in veins and capillaries, prinzmetal angina due to its ability to cause vasospasm due
decreasing preload, while the relaxation of the vessels to blocking of beta-receptor sites.
decreases afterload.  Nadolol (Corgard) are used for long-term management of
angina in adults.
INDICATIONS  Propranolol (Inderal) are used for long-term management
 These drugs are usually taken before chest pain begins in of angina and the prevention of reinfarction in patients 1-4
situations in which exertion or stress can be anticipated for weeks after myocardial infarction in adults.
prevention of angina in adults, it can also be taken daily for
management of chronic angina. It is also the relief of acute CONTRAINDICATIONS AND CAUTIONS
anginal pain in adults.  These drugs are contraindicated in patients with the
 For children, it may be used only for congenital heart following conditions:
defects and cardiac surgery because they can cause o Bradycardia, heart block and cardiogenic shock -
dangerous changes in blood pressure. blocking of the sympathetic response could
 For older adults, they are prone to adverse effects like exacerbate these diseases; and
arrhythmias and hypotension so safety measures should be o Pregnancy and lactation - potential adverse
instituted. They should be given an initial low dose because effects on the fetus or neonate.
of hepatic and renal impairments which can interfere with  Caution should be used in patients with the following
metabolism and excretion of drugs. conditions:
o Diabetes, peripheral vascular diseases, asthma,
CONTRAINDICATIONS AND CAUTIONS chronic obstructive pulmonary diseases (COPD)
 These drugs are contraindicated in the presence of any or thyrotoxicosis - due to the blockade of the
allergy to nitrates. sympathetic response prevents maintaining
 These drugs are also contraindicated in the following homeostatic requirements of these diseases.
conditions: o Patients given these drugs should be monitored
o Severe anemia - the decrease in cardiac output carefully to prevent serious adverse effects.
could be detrimental in a patient who already has DRUGS UNDER BETA-BLOCKERS
a decreased ability to deliver oxygen because of a  Beta-blocker agents include the following: nadolol
low red blood cell count; (Corgard), propranolol (Inderal) and the prototype drug
o Head trauma or cerebral hemorrhage - intracranial metoprolol (Toprol, Toprol XL).
bleeding may possibly happen due to the
relaxation of cerebral vessels; and CALCIUM CHANNEL BLOCKERS
o Pregnancy or lactation - potential adverse effects THERAPEUTIC ACTION
on the neonate and ineffective blood flow to the
fetus.  Drugs that block heart contraction through inhibition of
 Caution should be used in patients with the following movement of calcium ions, altering arterial and cardiac
conditions: muscle action potentials and blocking muscle cell
o Hepatic or renal disease - could alter the contraction.
metabolism and excretion of these drugs; and  Loss of smooth muscle tone, vasodilation and decreased
o Hypotension, hypovolemia and conditions that peripheral resistance occur.
limit cardiac output (tamponade, low ventricular  These drugs relieve coronary artery vasospasm and
filling pressure, low pulmonary capillary wedge increase blood flow to the muscle cells.
pressure) - results in serious adverse effects when
exacerbated. INDICATIONS
 These drugs are indicated for the treatment of Prinzmetal
DRUGS UNDER NITRATES angina, chronic angina, effort-associated angina and
 Nitrate includes the following agents: amyl nitrate hypertension.
(generic), isosorbide dinitrate (Isordil), isosorbide  Verapamil (Calan, Isoptin) is indicated also for the
mononitrate (Imdur, Monoket) and nitroglycerin (Nitro- treatment of tachyarrhythmias.
bid, Nitrostat, others) is the prototype drug.
CONTRAINDICATIONS AND CAUTIONS
BETA-BLOCKERS  Calcium channel blockers are contraindicated in the
THERAPEUTIC ACTION presence of the following conditions:
o Allergy to any of these drugs - to avoid
 They are also called sympatholytics.
hypersensitivity reactions; and
 These drugs block beta-adrenergic receptors in the heart
o Pregnancy or lactation - potential adverse effects
and juxtaglomerular apparatus, decreasing the stimulatory
on the fetus or neonate.
effects of the sympathetic nervous system on these tissues,
 Caution should be used on patients with the following
resulting in a decrease in excitability of the heart, a
conditions:
decrease in cardiac output, a decrease in cardiac oxygen
consumption and a lowering blood pressure. o Heart block or sick sinus syndrome - could be
exacerbated by the conduction-slowing effects of
these drugs;
 o Renal or hepatic dysfunction - alters the DRUGS UNDER ANGIOTENSIN-RECEPTOR NEPRILYSIN
metabolism and excretion of these drugs; and INHIBITORS (ARNIS)
o Heart failure - could be exacerbated by the  The angiotensin-receptor neprilysin inhibitors (ARNIs)
decrease in cardiac output that could occur. include Entresto.
DRUGS UNDER CALCIUM CHANNEL BLOCKERS
 Calcium channel blockers include the following agents:
amlodipine (Norvasc), nicardipine (Cardene), nifedipine NURSING CONSIDERATIONS
(Adalat, Procardia), verapamil (Calan, Isoptin) and the ASSESSMENT
prototype drug diltiazem (Cardizem, Cardizem SR). Focus
 Assess for contraindications or cautions: any known
drug information can be found on page 44 of this written
allergies to antianginals to avoid hypersensitivity reactions;
report.
impaired liver or kidney function that could alter the
metabolism and excretion of the drug; and any condition
ANGIOTENSIN-RECEPTOR NEPRILYSIN INHIBITORS (ARNIS)
that could be exacerbated by the hypotension and change
THERAPEUTIC ACTION in blood flow caused by these drugs such as early
 This drug is the result of combining two anti-hypertensive myocardial infarction, head trauma, cerebral hemorrhage,
drugs (sacubitril and valsartan) that reduce blood pressure. hypotension, hypovolemia, anemia, or low-cardiac output
 Commonly used for the treatment of heart failure and may states and current status of pregnancy or lactation.
improve length of life more than ACE-inhibitors.  Perform physical assessment to establish baseline status
 Valsartan blocks the receptors to which angiotensin II before beginning therapy and during therapy to determine
attaches, which is a hormone from the kidney that can be effectiveness and to evaluate for any potential adverse
harmful in patients with heart failure. This action stops the effects.
hormone’s harmful effects on the heart and allows the blood  Auscultate lungs to evaluate changes in cardiac output.
vessels to dilate or widen.  Inspect the skin for color, intactness and any signs of
 Sacubitril blocks the breakdown of natriuretic peptides redness, irritation or breakdown, especially if the patient is
which are produced in the body, it causes sodium and water using the transdermal or topical form of the drug to prevent
to pass into the urine. This action reduces the heart’s work possible skin reaction and ensure adequate surface for
and blood pressure through relaxation of blood vessels. application and absorption of transdermal or topical drug.
 The combined effect of the two drugs reduces the strain of  Measure capillary refill to evaluate presence of
the failing heart. insufficiencies in the peripheral vascular system.
 Assess the patient’s complaint of pain, including onset,
INDICATIONS duration, intensity, location and measures used to relieve it.
 This drug is currently used for the treatment of patients with  Assess the patient’s neurologic status including level of
heart failure with reduced function of the main pumping alertness, affect, reflexes for evaluation of CNS effects.
chamber or ejection fraction improvement.  Assess cardiopulmonary status including pulse rate, blood
 Used in place of an ACEI or angiotensin II receptor blocker pressure, heart rate and rhythm to determine effects of
(ARB) and together with other standard, heart-failure therapy and identify any adverse effects.
treatments.  Obtain an ECG as ordered for evaluation of heart rate and
 Patients must be able to tolerate ACEI or ARB before rhythm.
starting on sacubitril/valsartan.  Monitor laboratory test results to determine the need for
possible dose adjustment.
CONTRAINDICATIONS AND CAUTIONS
 This drug is contraindicated in patients with the following DIAGNOSIS
conditions:
 Decreased cardiac output related to vasodilation and
o Hypersensitivity to any component of the product.
hypotensive effects of the drug.
o Prior history of angioedema due to an ACEI or
 Risk for injury related to adverse effects on neurological
ARB, especially black patients and patients may
and cardiovascular status.
be at increased risk of angioedema with sacubitril
and valsartan.  Risk for injury related to possible alterations in CNS while
o Hypotension, hypovolemia, patients who are on drug therapy.
volume and salt depleted are at an increased risk  Ineffective Tissue Perfusion (Total Body) related to low
of developing hypotension. oxygen supply to myocardial cells, hypotension or change
o Diabetic patients receiving renin inhibitor, in cardiac output.
aliskiren, specifically, the valsartan component  Deficient knowledge regarding drug therapy.
and any ARB is contraindicated with aliskiren due
to an increased risk of hypotension, hyperkalemia IMPLEMENTATION
and renal impairment.
o Those who have received an ACE within 36 hours  Give the drug as ordered following safe and appropriate
due to increased risk of angioedema. administration to ensure therapeutic effects.
o Hepatic diseases because no studies have been  Monitor blood pressure, heart rate and rhythm to detect
conducted in patients who have severe hepatic possible development of adverse effects.
diseases so it is not recommended.  Give sublingual preparations under the tongue or in the
o Pregnancy and lactation because drugs that act buccal pouch, and encourage the patient not to swallow to
directly on the renin-angiotensin system can ensure that therapeutic effectiveness is achieved.
cause injury and death to the fetus or neonate.  Ask for the presence of a burning sensation to ensure
drug potency.
 Maintain drug potency through protecting the drug from
sunlight.
  Take drugs with water and do not crush for sustained  Offer support and encouragement to help the patient deal
release forms for these preparations to reach the GI tract with the diagnosis and drug regimen. Provide thorough
intact. patient teaching.
 Rotate injection sites and provide skin care as appropriate
EVALUATION
to prevent skin abrasion and breakdown.
 Avoid abrupt stop of long-term therapy because abrupt  Monitor the patient’s response to the drug/therapy.
withdrawal could cause a severe reaction, tapering the  Monitor for presence of adverse effects.
dose gradually over 4 to 6 weeks.  Evaluate the effectiveness of the teaching plan.
 Provide comfort measures through small frequent meals,  Monitor for compliance with the regimen and the
appropriate room temperature and lights, noise reduction, effectiveness of comfort measures.
ambulation assistance, reorientation, and skin care to help  Monitor laboratory tests.
the patient tolerate drug effects.

ANTIANGINAL AGENTS

NITROGLYCERIN
NITRATES

GENERIC NAME nitroglycerin

TRADE NAME Nitro-Bid, Nitrostat, others

IMAGE

Images from: https://www.boundtree.com/pharmaceuticals/non-narcotic-drugs/nitrostat/p/group001720,

https://www.goodrx.com/nitro-bid/what-is, https://www.medline.com/product/Nitroglycerin-Injection/Cardiac-
Medications/Z05-PF87067;ecomsessionid=EMZSAIfRMMIgs9z7h0-YzOIQ9RYWfOb_FeoMxo92.OC13-
b2b?_requestid=2639476, https://www.empr.com/drug/nitromist/, and
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=e98a2692-1cb9-4994-98d8-
1d8d9ef1a256&type=display

Indicated to prevent and treat angina or chest pain due to cardiovascular diseases as well as to treat perioperative
INDICATIONS hypertension or induce intraoperative hypotension. It is also indicated to treat acute heart failure in patients with
myocardial infarction.

 5 mcg/min via IV infusion pump every 3-5 min; one tablet SL every 5 min for acute attacks, up to three
tablets in 15 min
 0.4-mg metered dose translingual, up to three doses in 15 min for acute attacks
PREVENTION:
DOSAGE & FORMS  One tablet (0.3-0.6 mg) sublingually 5-10 min. Before activities that might precipitate an attack: 2.5-9mg
PO of SR tablet q8-12h;
 doses as high as 26 mg PO qid have been used;
 0.5 inches q8h for topical application, up to 4-5 inches (1inch=15mg) have been used;
 one pad (60-75 mg) have been used;
 one pad transdermal system per day, 1mg q3-5h while awake for the transmucosal system.

PHARMACOKINETICS

Rapidly absorbed through IV, sublingual, translingual, transmucosal, oral, topical, transdermal and is often used in
Absorption
emergency situations.

Distribution Volume of distribution is 3 L/kg.

Metabolism In the liver

Excretion Urine

Half-life 1 to 4 minutes
PHARMACODYNAMICS

 IV: 3-5 min

 Sublingual tablet: 30-60 min
 Translingual spray: 30-60 min
Duration  Transmucosal tablet: 3-5 min
 Oral, SR tablet: 8-12 h
 Topical ointment: 4-8 h
 Transdermal: 24 h

 IV: 1-2 min.

 Sublingual tablet: 1-3 min
 Translingual spray: 2 min
Onset  Transmucosal tablet: 1-2 min
 Oral, SR tablet: 20-45 min
 Topical ointment: 30-60 min
 Transdermal:30-60 min

Peak Effects Relaxation of vascular smooth muscle

The mitochondrial aldehyde dehydrogenase (mtALDH) converts nitroglycerin to nitric oxide, which is an active
substance that activates the enzymes guanylate cyclase. After the activation of the enzyme, it is followed by the
synthesis of cyclic guanosine 3’,5’-monophosphate (cGMP) which activates a cascade of protein kinase-dependent
Mechanism of
phosphorylation events in smooth muscles which leads to the dephosphorylation of the myosin light chain of smooth
Action
muscles that causes relaxations and increased blood flow in veins, arteries and cardiac tissue, resulting into
decreased work of the heart decreased blood pressure, relief of anginal symptoms and increased blood flow to the
myocardium.

ADVERSE EFFECTS Hypotension, headache, dizziness, tachycardia, rash, flushing, nausea, vomiting, sweating, chest pain.

 Ergot derivatives - risk for hypertension and decreased antianginal effects.

CLINICALLY  Heparin - risk of decreased therapeutic effects of heparin if these drugs are given together. Patients should
IMPORTANT DRUG- be monitored if this combination is used.
DRUG INTERACTIONS  Sildenafil, tadalafil, or vardenafil - drugs that are used to treat erectile dysfunction should not be combined
with nitrates because serious hypotension and cardiovascular events could occur.

METOPROLOL
BETA BLOCKERS

GENERIC NAME metoprolol

TRADE NAME Toprol, Toprol XL, Dutoprol, Kapspargo, Lopressor, Lopressor Hct

IMAGE

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Indicated to treat stable angina pectoris, hypertension, prevention of reinfarction in MI patients and treatment of
INDICATIONS
stable and symptomatic HF.

Usual Adult Dose for Hypertension:

 Metoprolol Tartrate Immediate Release Tablets:
DOSAGE & FORMS
 Initial dose: 100 mg orally per day in single or divided doses
 Maintenance dose: 100 to 450 mg orally per day
 Metoprolol Succinate Extended Release Tablets:
  Initial dose: 25 to 100 mg orally once a day
 Maintenance dose: 100 to 400 mg orally once a day
Usual Adult Dose for Angina Pectoris:
 Metoprolol tartrate immediate release tablets:
 Initial dose: 50 mg orally twice a day
 Maintenance dose: 100 to 400 mg per day
 Metoprolol succinate extended release tablets:
 Initial dose: 100 mg orally once a day
 Maintenance dose: 100 to 400 mg per day
Usual Adult Dose for Myocardial Infarction:
 Early Treatment:
 Initial dose: 5 mg IV every 2 minutes as tolerated for 3 doses.
 Patients tolerant of full IV dose (15 mg): 50 mg orally every 6 hours starting 15 minutes after the last IV
dose and continued for 48 hours.
 Patients intolerant of full IV dose (15 mg): 25 or 50 mg orally every 6 hours depending on the degree of
intolerance starting 15 minutes after the last IV dose or as soon as their clinical condition allows.
 Late Treatment:
 Maintenance dose: 100 mg orally twice a day
Usual Adult Dose for Congestive Heart Failure:
 Metoprolol succinate extended release tablets: 25 mg orally once a day (12.5 mg orally once a day in
patients with more severe heart failure); double dose every 2 weeks to highest tolerated dose or up to
200 mg orally once a day.
 Usual Pediatric Dose for Hypertension:
 Metoprolol succinate extended release tablets for 6 years or older:
 Initial dose: 1 mg/kg orally once a day (not to exceed 50 mg orally once a day)
 Maximum doseL 2 mg/kg (200 mg) orally once a day

PHARMACOKINETICS

Absorption When orally administered, is it almost completely absorbed in the gastrointestinal tract.

Distribution The reported volume of distribution of metoprolol is 4.2 L/kg

Metabolism In the liver

Excretion Urine

Half-life 3 – 4 hours

PHARMACODYNAMICS

Oral: 15-19 h
Duration
IV: 15-19 h

Oral: 15 min.
Onset
IV: Immediate

Oral: 90 min
Peak Effects
IV: 60-90 min

It competitively blocks beta-adrenergic receptors in the heart and kidneys that decreases the influence of the
Mechanism of
sympathetic nervous system on the tissues and the excitability of the heart. It also decreases cardiac output
Action
resulting in a lowered blood pressure and decreased cardiac workload.

Dizziness, vertigo, HF, arrhythmias, gastric pain, flatulence, diarrhea, vomiting, impotence, decreased exercise
ADVERSE EFFECTS
tolerance.

 Clonidine - a paradoxical hypertension occurs and an increased rebound hypertension with clonidine
CLINICALLY withdrawal may occur.
IMPORTANT DRUG-  Nonsteroidal anti-inflammatory drugs - a decreased antihypertensive effect can occur and the patient
DRUG INTERACTIONS should be monitored closely and given a dose adjustment if this combination is used.
 Epinephrine - an initial hypertensive episode followed by bradycardia will occur if combined with this.
 Ergot alkaloids - a possible peripheral ischemia will exist if combined with beta-blockers.
  Insulin or antidiabetic agents - there is a potential change in blood glucose levels and the patient will not
have the usual signs and symptoms of hypoglycemia or hyperglycemia to alert them to potential
problems.

Sacubitril and valsartan

ANGIOTENSIN RECEPTOR NEPRILYSIN INHIBITORS

GENERIC NAME Sacubitril and valsartan

TRADE NAME Entresto

IMAGE

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Indicated to reduce risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic
INDICATIONS
heart failure.

sacubitril/valsartan film-coated tablet:

DOSAGE & FORMS  24 mg/ 26 mg (low starting dose)

 49 mg/ 51 mg (recommended starting dose)
 97 mg/ 103 mg (target dose)

PHARMACOKINETICS

Absorption Administered orally and are highly bound to plasma proteins.

Distribution 103 and 75 L

Metabolism Metabolized by esterases to the active metabolite LBQ657

Excretion Through urine and feces

 Sacubitril: 1.4 hr
Half-life
 Valsartan: 9.9 hr

PHARMACODYNAMICS

Duration Varies

Onset Varies

Significant non-sustained increase in natriuresis, increased urine cGMP, and decreased plasma MR-proANP and
Peak Effects
NT-proBNP compared to valsartan

The sacubitril is a neprilysin inhibitor, neprilysin is responsible for the degradation of atrial and brain natriuretic
peptide; the cardiovascular and renal effects of sacubitril’s active metabolite in heart failure are attributed to the
Mechanism of
increased levels of peptides that are degraded by neprilysin. While valsartan is an angiotensin II receptor type I
Action
inhibitor which decreases blood pressure and blocks vasoconstrictor and aldosterone-secreting effects of
angiotensin II.

Greater than 10%:

 Hypotension (18%)
ADVERSE EFFECTS
 Hyperkalemia (12%)
 1-10%:
 Cough (9%)
  Dizziness (6%)
 Orthostasis (2.1%)
 Falls (1.9%)
Less than 1%
 Angioedema (0.5%), in black patients (2.4%)
 Hypersensitivity (rash, pruritus, anaphylaxis)

CLINICALLY
Coadministration of furosemide, warfarin, digoxin, carvedilol, amlodipine, omeprazole, hydrochlorothiazide,
IMPORTANT DRUG-
metformin, atorvastatin and sildenafil does not slater the systemic exposure to sacubitril, LBQ657 or valsartan.
DRUG INTERACTIONS

 HDLs enter the circulation as loosely packed lipids. It is

ANTILIPIDEMIC AGENTS either used for energy or for picking up remnants of fats and
cholesterol from LDL breakdown.
 Antilipidemics (antihyperlipidemics, lipid-lowering agents)  HDLs serve a protective role of cleaning up remnants in
are drugs or chemical agents used to treat hyperlipidemia, blood vessels.
which is a condition wherein the lipid levels in the blood is
increased. CHOLESTEROL
 Lipid-lowering agents vary depending on what type of lipid  Important for normal functioning of the body, but can be
has excessive levels in the blood. For example, fibrates act disease-causing
on high triglyceride levels by slowing down its production.  It is the base unit for the formation of steroid hormones and
 Antilipidemic drugs are classified into bile-acid for the formation and maintenance of cell membranes.
sequestrants, HMG-CoA reductase inhibitors, cholesterol  Also a precursor to bile acids, which is essential for fat
absorption inhibitors, and other lipid-lowering agents absorption
including fibrates and niacin.
 Every cell in the body has the metabolic capability of
producing cholesterol.
PHYSIOLOGY
 Hydroxymethylglutaryl-coenzyme A (HMG-CoA)
LIPIDS reductase is an important enzyme that regulates the early
 Lipids make up 18-25% of the body lean mass in adults. steps in the synthesis of cholesterol.
 It is also one of the important macromolecules and
macronutrients in the body. METABOLISM OF LIPIDS
 There are different types of lipids in the body, including: 1. Fats that are ingested are taken into the body as dietary
o Fatty Acids fats, and then broken down into different kinds of lipids (e.g.
o Triglycerides cholesterol, lipoproteins).
o Phospholipids 2. The presence of lipids in the duodenum stimulates
o Steroids contraction of the gallbladder which releases bile containing
o Eicosanoids bile acids and cholesterol among other complex
o Lipoproteins components.
 It serves a variety of functions, such as:  Bile acids have its equivalent bile salts which are
o Protection sodium and potassium salts.
o insulation 3. These components (bile acids and cholesterol) play a major
o energy reserve role in emulsification of fats, wherein it acts as a detergent
o important cell components that breaks up the fats into small components called
o precursor of hormones micelles.
o aids in digestion.  Micelles are the broken down form of fats that is
 Most common lipids involved in cardiovascular diseases absorbed by the walls of the small intestine.
and complications are lipoproteins and cholesterol. 4. After performing its function, bile is then reabsorbed and
recycled to the gallbladder and liver where it remains until it
LIPOPROTEINS is needed again for fat absorption.
 Produced in the liver; main function is to transport lipids 5. Since the plasma is mostly made up of water, fats in the
 Aggregate of lipids and proteins; different types of form of micelles cannot be directly and readily be absorbed
lipoproteins vary depending on its lipid-protein ratio by the small intestines. Instead, the brush enzymes of the
 Lipoprotein types that have well-known clinical implications small intestine packages micelles into a chylomicron that
are low-density lipoproteins (LDL) and high-density is absorbed by the small intestine and transported into the
lipoprotein (HDL). lymphatic system through lacteals and into the blood
 Other types include chylomicrons, very low-density circulation.
lipoproteins (VLDL), and intermediate-density lipoprotein  Chylomicrons are globules of lipids that are coated
(IDL). with proteins, which are hydrophilic, enabling them
 LDLs enter the circulation as a tightly packed globule of to pass through the plasma and be transported
different types of lipids (e.g. cholesterol, triglycerides) into the circulation.
surrounded by a protein. When it is broken down, its 6. The outermost, exposed layer of protein surrounding the
contents or remnants should be returned to the liver for chylomicron, called apoproteins, determines the fate of the
recycling. However, in some cases, these contents (such lipids being carried. Some are broken down into tissues to
as cholesterol) stays on the blood vessel causing be used for energy, some are stored in fat deposits, and
complications like formation of plaque (atherogenesis). some continue to be transported in the liver where they are
 further processed into other types of lipids such as containing LDL segments in the blood to replenish the cell’s
lipoprotein and cholesterol. cholesterol. This results in the decrease of LDL and
cholesterol levels in the blood.

INDICATION
 These drugs are used in patients with primary
hypercholesterolemia that is manifested by high
cholesterol and high LDL levels.
 It is used in adjunct therapy along with diet modifications
and exercise.

CONTRAINICATIONS & CAUTIONS

 These drugs are contraindicated to those who have allergy
to any bile acid sequestrant.
 It is also contraindicated in the following conditions:
o Complete biliary obstruction - prevents bile from
beings secreted into the intestine
o Abnormal intestinal function - can be
Figure. 2. Metabolism of lipids (Karch, 2011). aggravated or exacerbated by the presence of
these drugs
HYPERLIPIDEMIA o Pregnancy or lactation - potential decrease of
 It is characterized by increased concentration of lipids in the the absorption of fat and fat-soluble vitamins can
blood. be fatal to fetus
 An abnormal increase of lipids in the blood can cause
DRUGS UNDER BILE ACID SEQUESTRANTS
different complications (e.g. heart attack, stroke) and lead
to cardiovascular diseases such as hypertension,  Available bile acid sequestrant drugs include
atherosclerosis, coronary artery disease, carotid artery cholestyramine (Questran, Prevalite), colestipol
disease, sudden cardiac arrest, peripheral artery disease, (Colestid), and colesevelam (Welchol).
and microvascular disease.  The prototype drug of bile acid sequestrants is
 Hyperlipidemia is a prevalent condition across all countries cholestyramine.
and it also contributes to the leading cause of death which
is heart attack, as well as stroke (5th leading cause of HMG-COA REDUCTASE INHIBITORS
death).  This drug group is frequently referred to as “statins”; hence,
 It takes on different forms and its occurrence are caused all drugs under this group has a suffix of —statin to their
by: name. For example, atorvastatin and rosuvastatin.
o Excess levels of cholesterol  Most of these drugs are chemical modifications of
(hypercholesterolemia) compounds produced by fungi.
o Excess levels of triglycerides  Several of these statin drugs have been formulated as
(hypertriglyceridemia) combination therapy with other drugs. Simcor, for example,
o alterations in low-density lipoprotein (LDL) and is a combination of simvastatin and niacin.
high-density lipoprotein (HDL) levels.
 May be a result from excessive dietary intake of fats or THERAPEUTIC ACTION
genetic alterations in fat metabolism.
 The way these drugs work involves an important enzyme
 Hyperlipidemia as a result of excessive dietary intake can
needed for the synthesis of cellular cholesterol—
sometimes be treated solely by diet modifications, but those hydroxymethylglutaryl-coenzyme A (HMG-CoA)
that persist even after dieting and those that are genetically reductase.
linked are treated using drug therapy.
 Statin drugs inhibit or block the actions of this enzyme,
resulting in a shortage of cholesterol in the cell. The body
DRUG CLASSES compensates for this by increasing the absorption of
cholesterol and LDL from the blood. Thus, the total serum
BILE ACID SEQUESTRANTS
levels of cholesterol and LDL decreases.
THERAPEUTIC ACTION  At the same time, HDL levels increase slightly due to the
 It lowers LDL and cholesterol levels in the blood and usually alteration in fat metabolism. This also helps in the
used in conjunction with diet modification elimination or “clean up” of LDL remnants and cholesterol
 These bile acid sequestrants bind with bile acids in the in the blood.
intestine to form an insoluble complex that is then excreted  Since most concentrations of the statin drug undergo first-
in the feces. Thus, it increases the excretion of bile acids in pass (hepatic) metabolism, the effects of the drug are
the stool and decreases the concentration of bile acids in mostly observed in the liver.
the body.  These drugs are also believed to have an effect on
 Bile acids contain high levels of cholesterol, therefore atherogenesis, but its exact mechanism is still unknown.
cholesterol is also lost due to the increased excretion of bile
acids. INDICATION
 However, bile acids are essential for fat absorption so the  These drugs are used as adjuncts with diet and exercise for
liver compensates by using more cholesterol to create bile the treatment of hypercholesterolemia that is unresponsive
acids. Due to this, the hepatic intracellular cholesterol level to dietary restrictions alone.
falls, leading to an increased absorption of cholesterol-
 Pravastatin, lovastatin, and simvastatin may be used for  Used in combination therapy along with atorvastatin or
patients with coronary artery disease (CAD) to slow its simvastatin as treatment for familial hypercholesterolemia.
progression.
 Pravastatin, lovastatin, simvastatin, and atorvastatin may CONTRAINDICATIONS & CAUTIONS
also be used to prevent a first myocardial infarction (MI) in  Ezetimibe is contraindicated in patients with known allergy
patients who have multiple risk factors for developing CAD. to any components of the drug to avoid hypersensitivity
reactions.
CONTRAINDICATIONS & CAUTIONS  If used in combination with statins, it should not be used
 These drugs are contraindicated in the presence of allergy during pregnancy and lactation, or with severe liver
to any statins or to fungal byproducts or compounds. diseases as it may increase the known effects of statins
 It is also contraindicated in patients with active liver disease such as possible liver or renal failure.
or history of alcoholic liver disease as it may exacerbate the  The drug should be used in caution as monotherapy during
conditions which may lead to severe liver failure. pregnancy or lactation as its possible effects to fetus and
 Statin drugs can cross the placental barrier and may be neonate is still not known. Likewise, it should also be used
excreted in breastmilk so it is also contraindicated in in caution for elderly patients or patients with liver disease
pregnant or lactating women. This drug group is also because of its potential adverse effects.
labelled as pregnancy category X.
 Caution should be taken in patients with impaired endocrine
function because of the potential alteration in the formation OTHER LIPID-LOWERING AGENTS
of steroid hormones.  The following drugs do not fall into any of the
aforementioned drug classes but still function as lipid-
lowering agents.
DRUGS UNDER HMG-COA REDUCTASE INHIBITORS  Some of these have many different functions that are not
 The prototype drug of this drug class is atorvastatin centered on reduction of lipid levels.
(Lipitor), while other statins include: fluvastatin (Lescol),
lovastatin (Mevacor), pravastatin (Pravachol), and FIBRATES
simvastatin (Zocor). THERAPEUTIC ACTION
 These stimulate the breakdown of lipoproteins from the
tissues and their removal from the plasma. This results in a
CHOLESTEROL ABSOPRTION INHIBITORS decrease in lipoprotein and triglyceride synthesis and
 It is a new class of drugs to lower cholesterol levels which secretion.
was approved in 2003.
 The first and only drug included in this class is ezetimibe. INDICATION
 Unlike bile acid sequestrants and statins, ezetimibe has a  Used as adjunctive treatment along with diet to reduce
distinct mechanism to lower serum cholesterol levels. It also elevated LDL-C, Total-C, triglycerides, and Apo-B, and to
does not disrupt the absorption of fat-soluble nutrients, such increase HDL-C in adults with primary
as Vitamin A, D, E, and K hypercholesterolemia.
 It is also indicated to treat adults with severe triglyceridemia.
THERAPEUTIC ACTION
 Ezetimibe works by selectively targeting the sterol CONTRAINDICATIONS & CAUTIONS
transporter protein, Niemann-Pick C1-Like 1 (NPC1L1).  Contraindicated in patients with hypersensitivity to fibrates
The function of NPC1L1 protein is to form a complex with or to any chemical compound and derivatives of fibric acid.
cholesterol in the gastrointestinal tract and facilitate its  Highly contraindicated in patients with following conditions:
transport intracellularly. o Active hepatic disease
 The drug acts at the jejunal brush border of the small o Preexisting gallbladder disease
intestine where it blocks NPC1L1 from binding to o Severe renal/hepatic dysfunction
cholesterol; thus, it prevents the transport of dietary o Lactating or breastfeeding women
cholesterol thereby decreasing cholesterol delivery to the o Advanced age
liver and other cells. When this happens, there will be an
increased absorption of cholesterol from the blood and into DRUGS UNDER FIBRATES
the cell. This results in reduced cholesterol levels in the
blood.  Fibrate agents include fenofibrate (TriCor) and gemfibrozil
(Lopid).
 Aside from that, it is also believed that ezetimibe disrupts
the function of other protein complexes that are involved in  There is no prototype drug appointed, but one can
cholesterol absorption, including CAV1–annexin 2 represent the other since both of them are derivatives of
heterocomplex. fibric acid and have very similar mechanisms of action.

INDICATION
NIACIN (NICOTINIC ACID/VITAMIN B3)
 It is used as an adjunct with diet and exercise to reduce
cholesterol levels as either monotherapy or combined with  It is also used to treat hyperlipidemia by inhibiting the
HMG-CoA inhibitor or bile acid sequestrants. release of free fatty acids from adipose tissue.
 Used also as treatment for sitosterolemia in which it  It also increases the rate of triglyceride removal from
reduces elevated sitosterol and campesterol levels. plasma, and generally reduces LDL and triglyceride levels
o Sitosterolemia - a condition in which fatty while increasing HDL levels.
substances from vegetable oils, nuts, and other  It may also decrease the levels of apoproteins needed to
plant-based foods accumulate in the blood. form chylomicrons.
 CHOLESTYRAMINE
BILE ACID SEQUESTRANTS

GENERIC NAME Cholestyramine

TRADE NAME Questran, Prevalite

IMAGE

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75785dd208c8&type=display

It is used to reduce cholesterol levels in the blood as treatment for patients with primary hypercholesterolemia. It
INDICATIONS
can also be used for the relief of pruritus associated with partial biliary obstruction.
Cholestyramine is available in powder form and should be mixed with water or any non-carbonated fluids (e.g. fruit
juice).
 For pruritus:
o Adults/Elderly: 4-8 g daily, PO.
o Children (6–12 YRS): 240 mg/kg daily in 2-3 divided doses or calculated as percentage of the
DOSAGE & FORMS adult (70 kg) dose. Maximum: 8 g daily.
 For hyperlipidemia:
o Adults/Elderly: Initially, 4 g daily increased by 4 g at weekly intervals to 12-24 g daily in 1-4
divided doses, then adjusted as required. Maximum: 36 g daily.
o Children (6–12 YRS): 240 mg/kg daily in 2-3 divided doses or calculated as percentage of the
adult (70 kg) dose. Maximum: 8 g daily.
PHARMACOKINETICS

Absorption It is not absorbed by the body systemically. Its action is limited to their effects while they are present in the intestine.

Distribution Not available.

Metabolism Not available.

Excretion The insoluble complex formed by cholestyramine binding to bile acids is excreted directly in feces.

Half-life Not available.

PHARMACODYNAMICS

Duration Varies

Onset Varies

Peak Effects Varies, but is said to take effect after 21 days of adjunctive therapy.

It binds to bile acids in the intestine, forming an insoluble complex that is directly excreted in feces instead of
Mechanism of
reabsorption. This causes a decrease in bile acids and consequently, in hepatic intracellular cholesterol levels. As
Action
a result, there is an increased uptake of cholesterol-containing LDLs, thereby decreasing serum cholesterol levels.

 Headache, anxiety, fatigue, and drowsiness related to changes in serum cholesterol levels.
 Increased bleeding times related to decreased absorption of vitamin K and decreased production of
ADVERSE EFFECTS clotting factors.
 Vitamin A and D deficiencies related to decreased absorption of fat-soluble vitamins.
 Rash, muscle aches, and pain.
CLINICALLY
IMPORTANT DRUG-  Malabsorption of fat-soluble vitamins may occur.
DRUG INTERACTIONS  It can delay the absorption of thiazide diuretics, digoxin, warfarin, thyroid hormones, and corticosteroids.
NURSING CONSIDERATIONS

 Assess for known allergies to the drug to prevent hypersensitivity reactions.

 Assess for contraindications, especially biliary obstruction which may be exacerbated by the drug.
Assessment  Perform physical assessment to obtain and establish baseline data.
 Assess bowel elimination patterns, including frequency of stool passage and stool characteristics, to
identify possible constipation and fecal impaction.
Nursing diagnosis may include:
 Acute pain related to headache and GI effect
Diagnosis  Constipation related to GI effects
 Risk for injury related to CNS changes and potential bleeding
 Deficient knowledge regarding drug therapy.
 This drug should not be administered in dry (powder) form. It should be mixed with non-carbonated fluids
such as water and fruit juice.
 Give the drug before meals to ensure that the drug is in the GI tract with food.
 Administer other oral medications 1 hour before or 4-6 hours after the bile sequestrant to avoid drug-drug
interactions.
Implementation  Arrange bowel programs and provide comfort measures to help the patient tolerate the side effects of the
drug.
 Offer support and encouragement to help the patient deal with the diagnosis, drug regimen, and lifestyle
changes that may be necessary.
 Provide thorough patient teaching to enhance patient knowledge about drug therapy and promote
compliance.
 Monitor patient’s appropriate response to the drug, such as reduction in serum cholesterol levels.
 Monitor for adverse effects.
Evaluation  Evaluate the effectiveness of the teaching plan.
 Monitor the effectiveness of comfort measures and compliance with the drug regimen.

ATORVASTATIN
HMG-COA REDUCTASE INHIBITORS

GENERIC NAME Atorvastatin

TRADE NAME Lipitor, Adivast, Atorcad, Avamax, Atorwin, Bestatin, Itorvaz, Ator-10/Ator-20, Saatin, Xentor

IMAGE

Image from: https://www.pharmez.ph/product/lipitor-80mg-tablet/

Treatment of hypercholesterolemia in patients that are unresponsive to dietary restrictions alone. It is also used in
INDICATIONS the prevention of CAD in adults with multiple risk factors. It is also approved to lower cholesterol levels in children
ages 10-17 years old with genetic or familial hyperlipidemia.
Atorvastatin is available in film-coated tablets thus it should not be broken, crushed, dissolved, or divided.
DOSAGE & FORMS  Adults/Elderly: 10 mg/day PO with a possible dosage range of 10-80 mg/day.
 Children (10–17 YRS): 10 mg/day PO. Maximum: 20 mg/day.
PHARMACOKINETICS

Absorption It is rapidly absorbed in the GI tract. Due to the first-pass effect, bioavailability becomes 14%.
 Distribution Widely distributed. Its plasma protein binding is greater than 98%.

t is metabolized in the liver and transformed into its active derivatives and inactive metabolites. It also undergoes
Metabolism
extensive first-pass metabolism in the gastrointestinal mucosa and liver.

Excretion Primarily excreted in feces (biliary), but can also be excreted in breastmilk and urine.

Half-life 14 hours

PHARMACODYNAMICS

Duration 20-30 hours

Onset Slow onset, initial effect may take 3-5 days.

Peak Effects Time to reach its peak plasma concentration is 1-2 hours.

Mechanism of Inhibits HMG-CoA reductase enzyme that is essential in cholesterol synthesis. As a result, it causes a decrease in
Action serum cholesterol levels, LDLs, triglycerides, and an increase in HDL levels.

It can cross the placental barrier and be excreted in breastmilk; thus, caution is needed for pregnant and lactating
OTHERS
women. It is labelled as pregnancy category X.

ADVERSE EFFECTS  Headache, flatulence, abdominal pain, cramps, and constipation.

 Potential for cataracts, photosensitivity, myalgia, and rhabdomyolysis with acute renal failure.
 Increased risk of rhabdomyolysis if combined with erythromycin, cyclosporine, gemfibrozil, niacin, or
CLINICALLY antifungal drugs.
IMPORTANT DRUG-  Increased serum levels and resultant toxicity if combined with digoxin and warfarin.
DRUG INTERACTIONS  Increased estrogen levels can occur if this drug is taken along with oral contraceptives.
 Serum levels and risk of toxicity increase if combined with grapefruit juice.
NURSING CONSIDERATIONS

 Assess for allergy to any statins and to fungal byproducts and compounds.
 Assess for conditions that may be contraindicated, especially active liver disease and history of alcoholic
liver disease.
Assessment  Determine current pregnancy and lactation status of women of reproductive age, as it may pose adverse
effects to fetus or neonate.
 Perform physical assessment to obtain and establish baseline data.
 Determine laboratory test results, especially those of liver and renal function tests, to identify possible
toxicity and evaluate effectiveness.
Nursing diagnoses related to drug therapy may include:
 Disturbed sensory perception (visual, kinesthetic, gustatory) related to CNS effects
Diagnosis  Risk for injury related to CNS, liver, and renal effects
 Acute pain related to myalgia, headache, and GI effects
 Deficient knowledge regarding drug therapy
 It may be given at any time of the day but it is best to administer statin drugs at bedtime because the
highest rates of cholesterol synthesis occur between midnight and 5 AM. Thus, the drug should be taken
when it will be most effective.
 Monitor serum cholesterol and LDL levels, liver function, and renal function.
 Arrange for periodic ophthalmic examination to monitor cataract development.
Implementation  Encourage patients to make lifestyle changes to decrease the risk of developing CAD and other related
cardiovascular diseases, as well as to increase the effectiveness of the drug therapy.
 Withhold in any acute, serious medical condition that may suggest myopathy or may serve as a risk factor
for the development of renal failure.
 Provide comfort measures and offer support and encouragement to the patient.
 Provide thorough patient teaching.
 Monitor the patient’s response to the drug that may be indicated by:
o Lowering of serum cholesterol and LDL levels
o Prevention of first MI
o Slowing progression of CAD
Evaluation  Monitor for any adverse effects.
 Evaluate effectiveness of comfort measures and compliance to the drug regimen.
 Evaluate the effectiveness of teaching plan.
 EZETIMIBE
CHOLESTEROL ABSORPTION INHIBITORS

GENERIC NAME Ezetimibe

TRADE NAME Ezetrol, Nexlizet, Roszet, Vytorin, Zetia

IMAGE

Image from: http://www.rassopharma.ch/ezetrol-ezetimibe

Treatment for hypercholesterolemia to reduce cholesterol levels by either monotherapy or combination therapy
INDICATIONS
with other antihyperlipidemics. Also used to treat sitosterolemia by reducing sitosterol and campesterol levels.
Ezetimibe is available in tablet form and is taken orally.
DOSAGE & FORMS  Adults, Elderly, and Children (10 yrs and above): 10mg once daily.
 If taken with bile acid sequestrants, take ezetimibe at least 2 hours before or 4-6 hours after bile acid
sequestrant.
PHARMACOKINETICS

Absorption Well-absorbed following PO administration.

Distribution Widely distributed. Protein binding is greater than 90%.

Metabolism Ezetimibe is rapidly and extensively metabolized by the liver and the small intestine.

Excretion Excreted mainly in feces via bile, but metabolites are excreted in urine.

Half-life 22 hours

PHARMACODYNAMICS

Duration Not available.

Onset Moderate

Peak Effects The time it takes to reach its peak plasma concentration is 4-12 hours.

Ezetimibe works in the brush border of the small intestines to selectively block the sterol transporter protein from
Mechanism of
binding to cholesterol. Hence, it inhibits the absorption of dietary cholesterol, while not disrupting the uptake of fat-
Action
soluble nutrients.

OTHERS Pregnancy Category C

ADVERSE EFFECTS  Most common effects are mild abdominal pain and diarrhea.
 Headache, dizziness, fatigue, upper respiratory infection (URI), back pain, and muscle aches and pain.
 Increased risk of elevated serum levels of ezetimibe if taken with cholestyramine, fenofibrate, gemfibrozil,
CLINICALLY or antacids.
IMPORTANT DRUG-  Risk of toxicity increases if ezetimibe is taken with cyclosporine.
DRUG INTERACTIONS  Increased risk of cholethiasis if taken with any fibrates.
 Warfarin levels increase when taking ezetimibe.
NURSING CONSIDERATIONS

 Assess for allergy to any components of the drug.

 Assess for contraindications or cautions, especially liver dysfunction, advanced age, pregnancy, or
Assessment lactation.
 Perform physical assessment to obtain and establish baseline data.
 Monitor orientation, reflexes, respirations, lung sounds, and bowel patterns.
 Also monitor test results for serum levels of cholesterol and lipid levels, as well as liver function.
Nursing diagnosis may include:
Diagnosis  Disturbed Sensory Perception (Visual, Kinesthetic, Gustatory) related to CNS effects
 Acute Pain related to myalgia, headache, and GI effects
 Deficient knowledge regarding drug therapy
 Monitor serum lipid levels before and periodically during drug therapy.
 Monitor liver functioning to detect toxicity and possible liver damage.
 Encourage the need for lifestyle changes.
Implementation  Suggest the use of barrier contraceptives in women of reproductive age if ezetimibe is used with statins,
as it may cause fetal abnormalities.
 Provide comfort measures and offer support and encouragement.
 Provide thorough patient teaching.
 Evaluate appropriate patient response to drugs.
Evaluation  Monitor for adverse effects.
 Monitor effectiveness of comfort measures and evaluate compliance to regimen.
 Evaluate the effectiveness of the teaching plan.
FENOFIBRATE
FIBRATES

GENERIC NAME Fenofibrate

TRADE NAME Antara, Cholib, Fenoglide, Fenomax, Lipidil Supra, Lipofen, Tricor, Triglide

IMAGE

Image from: https://gamot2go.com/collections/anti-cholesterol/products/fenofibrate-capsule-200mg

Primarily used as treatment for severe hypertriglyceridemia, but can also be used as an adjunct with diet to
INDICATIONS
reduce lipid levels.
Fenofibrate is available in capsules and tablets and is taken orally along with food, as it increases the drug’s
absorption.
DOSAGE & FORMS  For severe hypertriglyceridemia:
o Adults/Elderly: 43-130 mg/day.
 For mixed hyperlipidemia or hypercholesterolemia:
o Adults/Elderly: 130 mg/day.
PHARMACOKINETICS

Absorption Readily absorbed from the GI tract; increased absorption with food. Bioavailability is approximately 81%

Distribution Widely distributed to most tissues. Plasma protein binding is approximately 99% to plasma albumin.

Metabolism Rapidly metabolized by tissues and plasma into its active metabolite and then further metabolized in the liver.

Excretion Mainly via urine (60% as metabolite) and feces (25%).

Half-life 10-35 hours

PHARMACODYNAMICS

Duration Unavailable

Onset Moderate

Peak Effects Peak plasma concentration: 2-8 hours

Mechanism of Stimulates peroxisome proliferator activated receptor alpha (PPARα) which increases lipolysis, especially VLDL
Action catabolism, thereby decreasing triglyceride levels, VLDL levels, and moderately increases HDL levels.

ADVERSE EFFECTS  May increase cholesterol excretion into bile, leading to cholelithiasis.
 Pancreatitis, hepatitis, thrombocytopenia, and agranulocytosis may occur rarely.
CLINICALLY
 May increase the effects of warfarin.
IMPORTANT DRUG-  Bile acid sequestrants may impede absorption.
DRUG INTERACTIONS  Cyclosporine may increase concentration and the risk of nephrotoxicity.
 Colchicine and statins may increase the risk of severe myopathy, rhabdomyolysis, and acute renal failure.
NURSING CONSIDERATIONS

 Assess for hypersensitivity, contraindications, and cautions.

 Obtain diet history, especially fat consumption.
 Determine serum cholesterol, triglycerides, and other laboratory results.
 Monitor for complaints of myopathy if taken with statins.
 Monitor and report for severe diarrhea, constipation, nausea, skin rash/irritation, insomnia, muscle pain, tremors, and dizziness.
NIACIN

GENERIC NAME Niacin, Nicotinic acid

TRADE NAME Advicor, Concept Ob, Irospan 24/6 Kit, Mvc-fluoride, Niacor, Niaspan, Niodan, Simcor, Vitafol-one

IMAGE

Image from: https://www.indiamart.com/proddetail/niaspan-22435924697.html

Used as monotherapy or combination therapy with simvastatin or lovastatin to treat primary hyperlipidemia and
INDICATIONS mixed dyslipidemia. Also used to treat severe triglyceridemia. It is also used as treatment for various conditions
including inflammatory acne, vasodilation, and prophylaxis of nicotinic acid deficiency.
Available in normal and extended-release tablets taken orally, but can also be administered via parenteral
administration.
DOSAGE & FORMS  For hyperlipidemia:
o Adult: Initially, 250 mg once daily in the evening. Maximum: 6 g daily.
o As extended-release tab: Initially, 500 mg at night, gradually increased according to response
to a maintenance of 1-2 g at bedtime.
PHARMACOKINETICS

Absorption Readily absorbed from the GI tract.

Distribution Widely distributed in body tissues and appears in breastmilk.

 Metabolism Metabolized into derivatives but its exact mechanism is not available in literature.

Excretion Excreted via urine.

Half-life 20-45 minutes.

PHARMACODYNAMICS

Duration 2-4 hours

Onset Rapid

Peak Effects  For immediate release: 45 minutes.

 For extended release: 4-5 hours.
Inhibits release of free fatty acids from adipose tissue, increases the rate of triglyceride removal from plasma, and
Mechanism of
generally reduces LDL and triglyceride levels while increasing HDL levels. It may also decrease the levels of
Action
apoproteins needed to form chylomicrons.

ADVERSE EFFECTS  Intense cutaneous flushing, nausea and abdominal pain.

 Increases serum levels of uric acid and may predispose patients to the development of gout.
NURSING CONSIDERATIONS

 Assess for hypersensitivity, contraindications, and cautions.

 Should be given at bedtime to make maximum use of nighttime cholesterol synthesis.
 If taken with bile acid sequestrants, it should be given 4-6 hours after bile acid sequestrant to ensure absorption.
 Monitor and report for any adverse effects and any signs of toxicity.

 May seal off small injuries and breaks in a blood vessel,

DRUGS AFFECTING BLOOD allowing the area to heal

COAGULATION PLATELET AGGREGATION

 Platelets circulating in the blood vessels adhere to the site
 Drugs affecting blood coagulation includes: of injury, due to the exposure to collagen and other
o Antiplatelet agents
substances under the endothelial lining of the vessel.
o Anticoagulants
 Once platelets stick to the site of injury, they release
o Thrombolytic agents
adenosine diphosphate (ADP) and chemicals that causes
o Others:
aggregation of platelets in the site
 Factor XIII
 ADP is a precursor of prostaglandins, from which
 Factor IX
thromboxane A2 is formed.
PHYSIOLOGY  Thromboxane A2 causes local vasoconstriction and further
platelet aggregation or adhesion, which leads to the
BLOOD
formation of a platelet plug in the site of injury
 Liquid connective tissue that consists of cells surrounded
by a liquid extracellular matrix called plasma INTRINSIC PATHWAY
 It functions to transport nutrients and wastes, for  Hageman Factor (factor XII) is activated after blood is
homeostasis regulation, and for protection or immunity such exposed to collagen – activated Hageman factor is also
as clotting. called factor XIIa – and triggers a cascade of reactions of
clot formation process, clot-dissolving process, and
BLOOD COAGULATION inflammatory response
 To clot or to form a solid state, in order to stop blood flow to  Factor XIIa causes the activation of factor XI (plasma
an area of injury in blood vessels thromboplastin antecedent [PTA]) and activates a series of
 Blood changing from a fluid to a solid state that serves to coagulants
plug injuries of vascular system o The cascade of clotting factors leading to clot
 Blood coagulation is a complex process that involves formation is called the intrinsic pathway
vasoconstriction, platelet clumping or aggregation, and a o Prothrombin -> thrombin -> breaks down
cascade of clotting factors produced in the liver that fibrinogen -> fibrin threads -> clot (thrombus)
eventually react to break down fibrinogen  Consists of:
o Clotting factors – substance formed in the liver that o Factor I – fibrinogen
react in a cascading sequence to cause formation o Factor II – prothrombin
of thrombin from prothrombin o Factor IX – Christmas factor
o Thrombin – breaks down fibrin threads from o Factor X – Stuart-Prower factor
fibrinogen to form a clot o Factor XI – plasma thromboplastin
o Factor XII – Hageman factor
VASOCONSTRICTION
 Narrowing or tightening of blood vessels aided by the small
muscles around their walls
 EXTRINSIC PATHWAY DRUG THERAPY ACROSS THE LIFESPAN
 Cascade of clotting factors in blood that has escaped the CHILDREN
vascular system to form a clot outside the injured blood  There is little research on the usage of anticoagulants in
vessel youngsters.
 Along with the intrinsic pathway, the clotting forms from both  If they are administered in children, the patient must be
inside and outside of the injured site of the blood vessel, closely watched to avoid severe bleeding caused by
maintaining the closed nature of the cardiovascular system medication interactions or changes in gastrointestinal or
 Consists of: liver function.
o Factor I – fibrinogen  Everyone who makes contact with the kid must understand
o Factor II – prothrombin the significance of injury prevention and safety procedures,
o Factor VII – stable factor as well as what to do if the child is wounded and starts to
o Factor X – Stuart-Prower factor bleed.
 When Heparin is administered to a child, the weight and
CLOT RESOLUTION AND ANTICLOTTING PROCESS age of the patient should be carefully identified first before
 To prevent any obstruction of blood vessels due to blood preparing the medication dose – it should be doubled
clots, the plasma content of blood in our body consists of checked by another nurse or healthcare provider before
anticlotting substances which stop the clotting reactions giving it to the patient. However, there is no clear research
occurring inside the body. about the safety of low-molecular-weight heparins
 For instance, Antithrombin III is a small protein molecule administered in children.
that inactivates the coagulation process – it stops the  Warfarin is prescribed to children who are about to have
formation of thrombin which consequently prevents the heart surgery. Once again, the dosage must be calculated
breakdown of the fibrin threads. depending on the child's weight and age should be
 There is another component in the plasma which is called constantly checked.
the plasmin or also known as fibrinolysin – plasmin is a  Currently, there are no clear instructions or indications
protein-dissolving agent that dissolves the fibrin structure of when using antiplatelets of thrombolytic drugs on children.
blood clots and allows arteries or vessels to open.
 The precursor cells of plasmin are called the plasminogen ADULTS
which is manufactured in the body’s liver, and it can be  Adult patients who have administered these medications
located in the plasma of the blood. Plasminogen is being should be taught (health teachings) on how to prevent any
transformed or converted into plasmin happens when the injuries just like when utilizing a razor, using a soft-bristled
Hageman Factor is being activated with the help of toothbrush to protect the gums, and avoiding contact
antidiuretic hormone (ADH), epinephrine, pyrogens, sports, as well as what to do if bleeding occurs; it should be
emotional stress, physical activity, and the chemicals applied with constant, firm pressure and contact a health
urokinase and streptokinase. care provider.
 The main role of plasmin located in the plasma of the blood  Before using these medications, the patient should always
is to maintain the blood vessels of the cardiovascular make sure to consult and report to their respective
system open and functional. healthcare provider because many other drugs are known
to interact with these kinds of agents.
 In the evaluation phase, the patient should be well-informed
of the significance of regular and periodic blood tests to
know the effects of the drug on the body.
 These medications are not advised to be prescribed to
pregnant women because there are known risks connected
to blood clotting when pregnant. However, if the benefit
outweighs the risks, the drug can be administered to them.
Additionally, these drugs are not advised when the mother
is breastfeeding.

OLDER ADULTS
 Several underlying medical disorders in older persons may
need the use of medicines that modify blood coagulation
such as coronary artery disease, cerebrovascular accident,
peripheral vascular disease, transient ischemic episodes.
 According to some studies, older adults who are
administered these medications are the ones who are most
likely to experience drug-drug interactions.
 The elderly are also more prone to have decreased liver
and renal function, which can change medication
metabolism and excretion.
 The lungs and uterus of females are found to be the organs  Before beginning therapy, the elderly person should be
with high levels of plasmin: lungs consist several of little, thoroughly examined for liver and renal function, usage of
easily injured capillaries. Uterus maintains pregnancy which other drugs, and capacity to comply with frequent blood
carries on the constant blood flow for the proper tests and medical examinations. Therapy should be begun
development of the fetus. at the lowest feasible dose and then increased based on
 During menstrual flow in women, the clots do not quickly the patient's reaction.
form in the lining of the uterus consequently blood flows  The patient's whole pharmacological prescription must be
slowly in a span of days, and therefore the role of plasmin carefully monitored. Manipulating such as starting,
is very significant in females.
 stopping, or modifying the amount of other medicine may platelet interactions, as well as preventing them to react
change the body's metabolism of the medication being with other clotting materials. These drugs block the receptor
utilized to impact coagulation, increasing the risk of sites found on the membrane of platelets to block the
bleeding, or rendering anticoagulation futile or interactions that may lead to clot formation.
unsuccessful.

DISORDERS AFFECTING BLOOD COAGULATION INDICATIONS

 Hemorrhagic diseases are those that have a direct impact  The antiplatelet agents are utilized in the treatment of
on the coagulation process. These illnesses are classified cardiovascular diseases with an increased risk for occluded
into two parts: thromboembolic disorders, which include the vessels, maintenance of venous and arterial grafts,
overproduction of clots, and situations in which the prevention of cerebrovascular occlusion, and functions as
coagulation mechanism is ineffective, resulting in the adjunction to thrombolytic therapy in the prevention and
danger of excessive bleeding (Karch, 2011). treatment of myocardial infarction (MI)

THROMBOEMBOLIC DISORDERS CONTRAINDICATIONS

 Medical diseases involving the production of thrombi lead  Contraindicated to patients with:
to reduced blood flow or complete occlusion or occlusion of o Presence of allergies – to avoid hypersensitivity
a certain blood vessel in our body. Thromboembolic reactions
diseases are conditions that predispose a person to the o Presence of bleeding disorder – risk of excessive
production of clots and emboli. blood loss
 There are also some cases in the hospital where some little o Recent surgery – risk of increased bleeding in
substances of thrombus (emboli) can break off and cross unhealed vessels
along with the cardiovascular system until such time that it o Closed head injuries – risk of bleeding from the
is trapped in a small blood vessel which blocks it up. injured vessels in the brain
 Due to the damaged endothelial lining of the blood vessels, o (No adequate studies) Pregnancy – potential for
the coronary arteries are being narrowed which leads to the increased bleeding
presence of coronary artery disease or CAD because the o Lactation – potential adverse effects on the fetus
thrombi most likely form in the damaged endothelial lining or neonate
of the vessel.
 The lumens of the vessels get smaller and narrower as the DRUGS UNDER ANTI-PLATELET AGENTS
damage accumulates. The coronary arteries become  Abciximab (Reopro)
restricted to transport sufficient blood to fulfill the demands  Anagrelide (Agrylin)
of the cardiac muscle over a period of time, and this is why  Aspirin
hypoxia occurs.  Cilostazol (Pletal)
 The blood flow to a specific area can be cut off when a blood  Clopidogrel (Plavix)
vessel gets very narrowed – clots occlude the vessel. If this  Dipyridamole (Persantine)
happens, necrosis, infarction, and anorexia can be  Eptifibatide (Integrilin)
observed and seen.  Sulfinpyrazone (Anturane)
 Several of the blood vessels in the body can be  Ticlopidine (Ticlid)
compromised as we age, causing similar difficulties with
 Tirofiban (Aggrastat)
constriction and blood supply. To avoid the creation of clots
in the system, these illnesses are treated with medications
ANTI-COAGULANTS
that interfere with the normal coagulation process.
 The drugs under anticoagulants interfere with the normal
HEMORRHAGIC DISORDERS coagulation by interfering with the cascade of clotting
factors and the formation of thrombin.
 Hemorrhagic diseases, which include excessive bleeding,
are less prevalent than thromboembolic disorders.
THERAPEUTIC ACTION
 Hemophilia, a hereditary absence of clotting factors; liver
illness, in which clotting factors and proteins are not  The anticoagulants interfere with the normal process of
generated; and bone marrow problems, in which platelets coagulation, which may prolong the process, or may inhibit
are not made in sufficient amounts to be functional, are or prevent the formation of clotting factors.
examples of these conditions.
 In these kinds of disorders, clotting factors and various DRUG INDICATIONS
medications are administered to increase the coagulation to  The antiplatelet agents are utilized to maintain a state of
cure and treat patients. anticoagulation in situations in which the patient is
susceptible to potentially dangerous clot formation; acute
treatment and prevention of venous thrombosis and
DRUG CLASSES pulmonary embolism, treatment of atrial fibrillation with
ANTI-PLATELET AGENTS embolization, prevention of clotting in blood samples and in
dialysis and venous tubing, and diagnosis and treatment of
 The drugs under antiplatelet agents decrease the formation disseminated intravascular coagulation (DIC).
of the platelet plugs by decreasing the responsiveness of
platelets to the stimuli that would cause them to aggregate. CONTRAINDICATIONS
THERAPEUTIC ACTION  Contraindicated to patients with:
o Presence of allergies – to avoid hypersensitivity
 The antiplatelet agents function by inhibiting platelet reactions
adhesion and aggregation by preventing the platelet-to-
 o Conditions that could be compromised by  Due to the site and nature of their molecules, they do not
increased bleeding tendencies (hemorrhagic greatly affect thrombin and clotting, and causes a fewer
disorders, GI ulcers, recent trauma, etc.) systemic adverse effect
o Warfarin for pregnant women – fetal injury and  It was also found that these drugs block angiogenesis, a
death have occurred process which allows cancer cells to develop new blood
o Lactation – potential risk to baby vessels, thus, they are being studied for its possibility to
o Renal or hepatic disease – could interfere with adjunct to cancer chemotherapy
metabolism and effectiveness of drug
THERAPEUTIC ACTION
DRUGS UNDER ANTI-COAGULANTS  Low-Molecular-Weight Heparins function to inhibit
 Antithrombin III (Thrombate III) thrombus and clot formation by blocking factors Xa and IIa.
 Argatroban (Acova)
 Bivalirudin (Angiomax) INDICATIONS
 Desirudin (Iprivask)  Indicated for very specific uses in the prevention of clots
 Fondaparinux (Arixtra) and emboli formation after certain surgeries or prolonged
 Heparin (generic) bed rest
 Warfarin (Coumadin)  Prevention and treatment of DVT following hip or knee
replacement or abdominal surgery, unstable angina, acute
THROMBOLYTIC AGENTS coronary syndromes
 Thrombolytic agents perform the process of clot resolution,  The drug is given just before (or just after) the surgery and
wherein the thrombus is broken down by stimulating the then is continued for 7 to 14 days during the postoperative
plasmin system. recovery process

THERAPEUTIC ACTION CONTRAINDICATIONS

 Thrombolytic agents act by activating the natural anti-  Contraindicated to patients with:
clotting system, the conversion of plasminogen into o Presence of allergies – to avoid hypersensitivity
plasmin. Once the plasmin system is activated, fibrin reactions
threads are broken down and formed clots are dissolved. o Presence of bleeding disorder – risk of excessive
blood loss
INDICATIONS o Severe and uncontrolled hypertension
 The thrombolytic agents are utilized for the lysis of o Pregnancy and breastfeeding women
pulmonary emboli, treatment coronary thrombosis, clearing o Liver or renal disease
occluded intravenous catheters, treatment of MI, acute  Caution must be used to avoid combining these drugs with
pulmonary embolism, and acute ischemic stroke; standard heparin therapy; serious bleeding episodes and
restoration of function in occluded central venous access deaths have been reported when this combination was
devices inadvertently used

CONTRAINDICATIONS DRUGS UNDER LOW MOLECULAR WEIGHT HEPARIN

 Contraindicated to patients with:  Dalteparin
o Presence of allergies – to avoid hypersensitivity  Enoxaparin
reactions  Tinzapar
o Conditions that could be worsened by the
dissolution of clots (recent surgery, aneurysm, ANTICOAGULANT ADJUNCTIVE THERAPY
recent major trauma, etc.)  Coagulation treatment used to assist a primary treatment
o Liver disease – could affect normal clotting factors  Agents used include lepirudin, protamine sulfate, and
and the production of plasminogen vitamin K
o Pregnant women – possible adverse effects on the  Lepirudin (Refludan)
fetus or neonate o IV drug developed to treat a rare allergic reaction
o Should not be used during pregnancy unless the to heparin
benefits to the mother clearly outweigh the o In some patients, an allergy to heparin precipitates
potential risks to the fetus a heparin-induced thrombocythemia with
o Lactation – potential risk for bleeding effects in the associated thromboembolic disease.
nursing baby o Lepirudin directly inhibits thrombin, blocking the
thromboembolic effects of this reaction
DRUGS UNDER THROMBOLYTIC AGENTS o It forms a stable non-covalent complex with alpha-
 Alteplase (Activase) thrombin, inhibiting it from cleaving fibrinogen and
 Reteplase (Retavase) starting the clotting cascade
 Streptokinase (Streptase) o Administered IV bolus and IV infusion
 Tenecteplase (TNKase)  Initial: 0.4-mg/kg initial IV bolus
 Urokinase (Abbokinase)  Followed by a continuous infusion of 0.15
mg/kg for 2 to 10 days
OTHER DRUGS AFFECTING CLOT FORMATION o Patient needs to be monitored for bleeding from
any site and for the development of direct hepatic
LOW-MOLECULAR-WEIGHT HEPARINS
injury
 Developed in the late 1900s, these drugs function to inhibit
thrombus and clot formation by blocking factors Xa and IIa
 HEMORRHEOLOGIC AGENT DRUGS USED TO CONTROL BLEEDING
THERAPEUTIC ACTION  Diseases which are involved with bleeding are administered
 The drugs under the hemorheological agents are the kinds with medications with clotting factors and regulates the
of medication that are responsible to improve or enhance process of blood coagulation such as antihemophilic
the arterial blood flow, and they are being utilized to treat agents and hemostatic agents. Bleeding disorders
intermittent claudication which is the cramping that happens include:
in the legs due to the lowered blood supply when doing o Hemophilia - the patient is very vulnerable with
physical activities (Sruthi, 2021). too much bleeding if he/she had any injuries due
to the lack of genetic clotting factors in the blood.
INDICATIONS o Liver Disease - if the liver is damaged due to other
diseases, the proteins and clotting factors of the
 Drugs under this drug class can improve limb function and
blood are not manufactured well.
alleviate illness symptoms.
o Bone marrow Disorders - if the patient has any
 These can increase the amount of oxygen that the
bone marrow related diseases, the platelets
circulation can give when the muscles demand more just
cannot be made adequately for the body to be
like during exercise), resulting in increased walking
functional for blood clotting.
distance and stamina.

CONTRAINDICATIONS
ANTIHEMOPHILIC AGENTS
 Contraindicated to patients with:
 According to Zaiden (2020), antihemophilic agents are
o Bleeding history - retinal bleeding, peptic ulcer,
utilized to manage the bleeding disorders of patients who
and preoperative patients.
have hemophilia B or factor IX deficiency in the blood. Also,
o Creatinine clearance of <30 mL/min
these medications regulate or control the bleeding in
o Allergy to xanthine derivatives such as caffeine,
patients who have hemophilia A and factor VIII inhibitors.
theophylline, and theobromine.
o Acute myocardial infarction or severe coronary
THERAPEUTIC ACTIONS
disease.
o Severe liver disease and cirrhosis.  These agents are utilized to treat hemophilia as they act to
 Caution must be performed tp: replace the factors which are genetically absent or low in a
o Not advised to patients 18 years old and below certain type of hemophilia either hemophilia A or hemophilia
because there are no studies yet about its safety B; the drug of choice under this class solely depends on the
for 18 years old and below. kind of hemophilia. Management and treatments for the
o Older adults are seen to have a higher plasma classic hemophilia such as administering antihemophilic
level which can lead to toxicity. factor and antihemophilic factor recombinant drugs is
o The drug’s metabolites are secreted in milk - this providing a non-permanent or temporary substitute of
drug falls under category C for pregnant women. clotting factors in order to repair or avoid bleeding episodes
or to permit surgery if needed (Karch, 2011).
ACTIVATED PROTEIN C
INDICATION
THERAPEUTIC ACTION
 Coagulation Factor VIIa and Factor IX are being utilized for
 Activated protein C or APC has been shown in previous
individuals with cases of hemophilia A or B. Coagulation
research findings to neutralize or inactivate factors (F) Va
factor VIIa contains preparations coming from the mouse,
and VIIIa, hence decreasing thrombin production. Current
hamsters, and bovine protein which are known to elicit
fundamental and preclinical studies on APC have defined
clotting factors. On the other hand, coagulation factor IX is
the immediate cytoprotective effects of APC, which include
composed of various components of other clotting factors
changes in gene expression data, anti-inflammatory and
which also elevates the blood levels of factors II, VII, IX, and
anti-apoptotic actions, and endothelial barrier preservation
X. the coagulation abnormalities should be established first
or stability (Griffin et al., 2007).
before choosing what kind of drug is being administered to
the patient.
INDICATIONS
 The medications under this class aids in the decrease of CONTRAINDICATION
inflammation and the formation of blood clots in blood
 The contraindications and cautions of the drug class are as
vessels in patients suffering from life-threatening
follows:
pathogenic illnesses. It also hastens blood clot
o The antihemophilic factor is contraindicated if the
disintegration.
patient has presence of allergies to mouse
 These medications are used to reduce the death rate in
proteins because it can cause hypersensitivity
people who have sepsis.
reactions.
o Factor IX is contraindicated if the patient has liver
CONTRAINDICATIONS AND CAUTIONS
disease with fibrinolysis that causes further
 Allergic to any ingredient of drotrecogin alfa. aggravation of the present disease.
 History or present internal bleeding. o Coagulation factor VIIa is contraindicated if the
 Presence of brain tumor or lesions. patient has presence of allergies to mouse
 Experienced stroke for the last 3 months. proteins because it can cause hypersensitivity
 Had brain or spinal cord surgery. reactions.
 Experienced severe head injury.  Caution to use the drugs during pregnancy or lactation
 Using an epidural catheter. because of the possible occurrence of adverse effects for
the baby or fetus; only prescribed to pregnant women when
the benefit outweighs the risks.
 DRUGS ANTIHEMOPHILIC AGENTS arachnoid hemorrhage. For the topical hemostatic agents,
 Antihemophilic factor (Bioclate) its indication to regulate or control the bleeding from the
 Antihemophilic factor, recombinant (Advate) surface injury of the patient.
 Coagulation factor VIIa (NovoSeven)
CONTRAINDICATION
 Factor IX complex (BeneFix)
 For systemic hemostatic agents, it is contraindicated if the
HEMOSTATIC AGENTS patient has an allergy to the drug which can cause
 According to Karch (2011), under certain cases, a hypersensitivity reactions. There is also a risk for
fibrinolytic condition with increased plasminogen activity arrhythmias for patients who have any cardiac diseases.
and the danger of bleeding from clot dissolution occurs. Conditions such as hepatic and renal impairments can alter
Patients having recurrent coronary artery bypass graft the process of elimination of the drug together with its
(CABG) surgery, for instance, are more vulnerable to clotting formation. The safety use of this medication to
severe bleeding and may necessitate blood transfusion. To pregnant women is not yet established which is why this
halt bleeding, hemostatic drugs are utilized. Hemostatic drug is only prescribed if the benefit outweighs the risk of
medications can be administered via systemic or topical. adverse effects to the baby. For topical hemostatic agents,
the drug is contraindicated if the patient has an allergy to
THERAPEUTIC ACTIONS bovine products.
 For systemic hemostatic agents, this kind of medication can DRUGS UNDER HEMOSTATIC AGENTS
be administered to avoid the body-wide or systemic
breakdown of clot in which to prevent the severe blood loss  Under Systemic Hemostatic Agents
if there are cases of systemic bleeding or hyperfibrinolysis. o Aminocaproic acid (Amicar)
However, the systemic hemostatic agents are only used  Under Topical Hemostatic Agents
and available for clinical usage in the United States. o Absorbable gelatin (Gelfoam)
 For topical hemostatic agents, this kind of medication is o Human fibrin sealant (Artiss)
administered in situations when surface injuries are very o Human fibrin sealant (Evicel)
much damaged to the point that the small vessels in the o Microfibrillar collagen (Avitene)
area are not clotting and the blood is constantly lost. o Thrombin (Thrombostat, Thrombonar)
Additionally, topical hemostatic agents are given to patients o Thrombin recombinant (Recothrom)
who are suffering from decubitus ulcers to serve as a care
for the presence of any wounds.

INDICATION
 For systemic hemostatic agents, its indication is to treat an
excessive bleeding in hyperfibrinolytic cases of patients, it
also prevents the exacerbation of bleeding related to

ASPIRIN
ANTI-PLATELET AGENTS

GENERIC NAME Aspirin / Acetylsalicylic acid (ASA)

TRADE NAME Aggrenox, Alka-seltzer, Aspilets, Durlaza

IMAGE

Image from: https://www.unilab.com.ph/products/aspilets

Reduction of risk of recurrent transient ischemic attacks (TIAs) or strokes in men with a history of TIA due to fibrin
INDICATIONS or platelet emboli; reduction of death or nonfatal MI in patients with a history of infarction or unstable angina; MI
prophylaxis; also used for its anti-inflammatory, analgesic, and antipyretic effects

Taken orally; 80 – 325 mg/day for revascularization; 162.5 mg of Durlaza, once daily for myocardial infarction (MI)
DOSAGE & FORMS
and risk reduction of stroke

PHARMACOKINETICS

Absorption Well-absorbed
 Distribution Highly bound to plasma proteins, particularly albumin

Metabolism Liver

Excretion Urine

Half-life 15 – 20 minutes

PHARMACODYNAMICS

Duration 4-6 hours

Onset 1 hour

Peak Effects 2-4 hours

ASA interferes with thromboxane A2 (TXA2), an inducer of platelet aggregation, by inhibiting COX-1. ASA blocks
Mechanism of prostaglandin synthesis. It inhibits COX-1, which results in the inhibition of platelet aggregation for about 7-10
Action days. It prevents the production of prostaglandins, which then halts the conversion of arachidonic acid to
thromboxane A2 (TXA2), a potent inducer of platelet aggregation.

The most common adverse effect of aspirin is bleeding. Nausea, dyspepsia, heartburn, epigastric discomfort, GI
ADVERSE EFFECTS
bleeding, occult blood loss, dizziness, tinnitus, difficulty hearing, anaphylactoid reaction

CLINICALLY  Risk of excessive bleeding increases if aspirin is combined with another drug that affects blood clotting
IMPORTANT DRUG-  NSAIDS may increase GI effects (ulceration)
DRUG INTERACTIONS  Antacids and urinary alkalizers increase excretion

NURSING CONSIDERATIONS

 Assess for conditions which could be cautions or contraindications of using the drug (allergy to aspirin, pregnancy or lactation,
bleeding disorders, recent surgery or closed head injury)
 Suggest safety measures to decrease risk of bleeding
 Report ringing of the ears or persistent abdominal GI pain, bleeding

HEPARIN
ANTI-COAGULANT

GENERIC NAME heparin

TRADE NAME Heparin Leo

IMAGE

Image from: https://dvago.pk/products/heparin_5000i_5ml_1s

Prevention and treatment of venous thrombosis and pulmonary emboli; treatment of atrial fibrillation with
INDICATIONS
embolization; diagnosis and treatment of DIC; prevention of clotting in blood samples and heparin locksets

Heparin has various administrations such as: IV or IV bolus, and SQ (subcutaneous)

 10,000–20,000 units SQ, then 8,000–10,000 units q8h
DOSAGE & FORMS  5,000–10,000 units IV pulmonary embolus, atrial fibrillation with embolization; q4–6h
Pediatric:
 50 units/kg IV bolus, then 100 units/kg IV q4h

PHARMACOKINETICS
 Absorption Given parenterally (IV or SQ) and not well absorbed in the GI tract

Distribution 40-70 mL/min (approximately the same as blood volume); extensively bound by globulins and fibrinogens

Metabolism Liver and reticuloendothelial system

Excretion Urine

Half-life 30 to 180 minutes

PHARMACODYNAMICS

 IV: 2-6 hours

Duration
 SQ: 8-12 hours

 IV: Immediate
Onset
 SQ: 20-60 minutes

 IV: Minutes
Peak Effects
 SQ: 2-4 hours

Heparin inhibits reactions that lead to the blood clotting and formation of fibrin clots, and inhibit thrombosis
through inactivation of factor Xa and thrombin. Heparin binds to antithrombin III (ATIII), which leads to inactivation
Mechanism of
of thrombin (factor IIa) and factor Xa, and can also inactivate factors IX, XI, XII and plasmin. It accelerates the
Action
rate of neutralization of certain activated coagulation factors by antithrombin. It prevents progression of existing
clots by inhibiting further clotting.

ADVERSE EFFECTS Loss of hair, bruising, chills, fever, osteoporosis, suppression of renal function (with long-term use)

CLINICALLY  Increased bleeding can occur if heparin is combined with oral anticoagulants, salicylates, penicillin, or
IMPORTANT DRUG- cephalosporins.
DRUG INTERACTIONS  Decreased anticoagulation can occur if heparin is combined with nitroglycerin

NURSING CONSIDERATIONS

 Assess for conditions that could be exacerbated by increased bleeding tendencies

 Evaluate for therapeutic effects of heparin—whole blood clotting time (WBCT) 2.5 to 3 times control or activated partial
thromboplastin time (APTT) 1.5 to 3 times the control value—to evaluate the effectiveness of the drug dose

UROKINASE
THROMBOLYTIC AGENTS

GENERIC NAME urokinase

TRADE NAME Kinlytic

IMAGE

Image from: http://pharmacistconnection.com/images/ch/imarx/full_printable.pdf

Lysis of pulmonary emboli or pulmonary emboli with unstable hemodynamics in adults, acute thrombi obstructing
INDICATIONS coronary arteries, occlusive thromboemboli in peripheral arteries and grafts, and restoration of patency to
intravenous catheters.

DOSAGE & FORMS Administered IV; 4400–10,000 units/min for up to 2 hours, based on clinical response

PHARMACOKINETICS

Absorption IV route; high bioavailability

 Distribution It has a volume of distribution of 11.5L

Metabolism Metabolized in the plasma by proteases to smaller proteins and amino acids

Excretion Bile and urine

Half-life Approximately 20 minutes

PHARMACODYNAMICS

Duration N/A

Onset Immediate

Peak Effects End of injection

Mechanism of Urokinase is a serine protease that functions by converting plasminogen to the active fibrinolytic protease,
Action plasmin.

Headache, angioneurotic edema, hypotension, skin rash, bleeding, breathing difficulties, bronchospasm, pain,
ADVERSE EFFECTS
fever, anaphylactic shock

CLINICALLY
IMPORTANT DRUG- The risk of hemorrhage increases if thrombolytic agents are used with any anticoagulant or antiplatelet drugs.
DRUG INTERACTIONS

NURSING CONSIDERATIONS

 Assess for conditions that could be worsened by the dissolution of clots

 Discontinue heparin if it is being given before administration of a thrombolytic agent, unless specifically ordered for coronary
artery infusion

ENOXAPARIN
LOW MOLECULAR WEIGHT HEPARINS

GENERIC NAME enoxaparin

TRADE NAME Lovenox

IMAGE

Image from: https://allmedtech.com/lo12bprsy10b.html.

 Prevention of DVT that may lead to PE after hip replacement or abdominal surgery
 With warfarin to treat acute DVT or PE
INDICATIONS
 Prevention of ischemic complications of unstable angina or non–Q-wave MI
 Prevention of DVT in patients with severely restricted mobility due to illness

Administered SQ
 Hip surgery: 30 mg SQ q12h for 7–10 days
DOSAGE & FORMS  Abdominal surgery: 40 mg/d SQ for 7–10 days
 DVT or PE: 1 mg/kg SQ q12h
 Angina: 1 mg/kg SQ q12h
 Prevention of DVT in high-risk patients: 40 mg/d SQ for 6–14 days

PHARMACOKINETICS
 Absorption Well absorbed

Distribution It has a volume of distribution of approximately 4-5L

Metabolism Liver

Excretion Urine

Half-life 4.5-7 hours

PHARMACODYNAMICS

Duration 12 hours

Onset N/A

Peak Effects 3-5 hours

Enoxaparin binds to antithrombin III to form a complex that inactivates factor Xa. After Xa inactivation, enoxaparin
Mechanism of
is released and binds to other anti-thrombin molecules. The cascade of effects from enoxaparin binding causes
Action
the thrombin to lose ability to convert fibrinogen to fibrin which forms the clot.

OTHERS

ADVERSE EFFECTS Allergic reactions (rash, urticaria), arthralgia, pain and inflammation at injection site, peripheral edema, fever

CLINICALLY Aspirin, NSAIDs, warfarin can increase risk of hemorrhage

IMPORTANT DRUG-
DRUG INTERACTIONS

NURSING CONSIDERATIONS

 Assess for conditions that could be worsened by the dissolution of clots

 Discontinue heparin if it is being given before administration of a thrombolytic agent, unless specifically ordered for coronary artery
infusion

PENTOXIFYLLINE
HEMORRHEOLAGI AGENT

GENERIC NAME pentoxifylline

TRADE NAME Trental

IMAGE

Photo Reference: https://www.drugs.com/pro/trental.html

 The drug Pentoxifylline is being utilized to treat intermittent claudication which is a pain that affects the
lower extremities (usually the calves but not common in the thighs and buttocks) with patients who are
suffering from chronic occlusive vascular disease.
 This drug can enhance limb function and relieve symptoms of the disease.
INDICATIONS
 This improves the quantity of oxygen that the circulation can provide when the muscles require more (for
example, during exercise), hence boosting walking distance and endurance.
 Take note that this medication is not a substitute for other treatments just like surgical bypass or vascular
blockage removal.

 400 mg; three times a day for at least 8 weeks.

DOSAGE & FORMS  Oral administration
 Administered with meals
PHARMACOKINETICS

 Because of substantial first-pass metabolism, oral pentoxifylline (PTX) has a poor bioavailability of 20-
30%.
Absorption
 Three of the seven known metabolites, M1, M4, and M5, are detectable in plasma and show immediately
after dosage.

Distribution An estimated 45% of the medication is bound to the erythrocyte membranes.

Metabolite l (1-[5-hydroxyhexyl]-3,7-dimethylxanthine) and Metabolite V (1-[3-carboxypropyl]-3,7-

Metabolism dimethylxanthine) are the primary metabolites, and plasma concentrations of such metabolites are 5 and 8 times
higher, correspondingly, with pentoxifylline.

 The medication is eradicated in the body mostly in the urine which is about 57% and 65% of the
Excretion administered dose to the patient.
 On the other hand, about 4% of the administered medication is being eliminated as feces.

Half-life Between 0.39 and 0.84 hours.

PHARMACODYNAMICS

Even though patients may feel the effects of this medicine in 2-4 weeks, it may take up to 8 weeks for the entire
Duration
impact of pentoxifylline to be felt.

Onset After oral treatment, pentoxifylline is virtually entirely absorbed.

Plasma levels of the parent substance and its metabolites reach a peak in 2 to 4 hours and then remain steady for
Peak Effects
a lengthy period of time.

 Pentoxifylline or PTX is a known synthetic dimethylxantine derivative in which regulates the rheological
components of the blood.
 This medication has anti-oxidant properties and anti-inflammatory properties.
 This drug was initially made as a treatment for intermittent claudication, recent studies have shown that
this drug was also observed to have a probable use in cases of diabetic kidney disease,
osteoradionecrosis, and conditions connected with fibrosis.
Mechanism of  With regards to the recent studies, PTX was also regarded and suggested as a probable medication for
Action pulmonary complications due to COVID-19 because the drug was seen to have the capacity to control
the manufacturing of inflammatory cytokines.
 PTX has the ability to decrease the blood viscosity through elevation of erythrocyte flexibility, lessen the
plasma fibrinogen formation, and suppress platelet aggregation.
 However, the exact and accurate mechanism of this drug is still not known.
 This drug has been regarded as one of the few medications which are effective in curing intermittent
claudication which is a very painful vascular disease occurring in the legs or lower extremities.

OTHERS

Nausea and vomiting, dizziness, headache, easy bruising or bleeding, rapid or irregular heart rate, abdominal
ADVERSE EFFECTS pain, loss of appetite, chest pain, low neutrophil count (neutropenia), low RBC count (anemia), inflammation of the
brain, hepatitis, increase in liver enzymes, blurred vision, anaphylaxis.

 Other medicines that might induce bleeding/bruising (including antiplatelet pharmaceuticals like
CLINICALLY
clopidogrel, NSAIDs like ibuprofen / ketorolac / naproxen, and "blood thinners" like warfarin / dabigatran)
IMPORTANT DRUG-
may react with this drug.
DRUG INTERACTIONS
 If utilized with this drug, aspirin can raise the danger of bleeding.

NURSING CONSIDERATIONS

 Patients with comorbidities such as cardiovascular complications should be monitored from time to time.
 Assess for symptoms such as headache, dizziness, nausea, and upset stomach.
 Administer the drug three times a day for 8 weeks to properly evaluate its effectiveness.

DROTRECOGIN ALFA
ACTIVATED PROTEIN C

GENERIC NAME drotrecogin alfa

TRADE NAME Xigris

IMAGE

Photo Reference: http://wakehealthse3.adam.com/content.aspx?productId=50&pid=50&gid=1722

 Drotrecogin alfa helps in the reduction of inflammation and the development of blood clots in blood
vessels in individuals with critical, deadly pathogenic infections. It also hastens the dissolution of blood
INDICATIONS
clots.
 This drug is being utilized in lowering the mortality rate in patients who experienced sepsis.

 The medication is only approved for adults who are suffering from severe sepsis which can lead to
DOSAGE & FORMS death.
 Usual dosage is 24 mcg/kg per hour in IV infusion for 96 hours.

PHARMACOKINETICS

Absorption

Distribution

Metabolism

Excretion

Half-life 5.5 hours in mammalian reticulocytes (in vitro)

PHARMACODYNAMICS

Duration IV infusion for 96 hours.

This medication is a kind of activated human protein C produced by recombinant DNA technology. It is a
glycoprotein with a molecular weight of around 55 kilodaltons that consists of a heavy chain and a light chain
joined through a disulfide bond.
Mechanism of
Action  Drotrecogin alfa suppresses factor Va and VIIIa which results in lowering blood coagulability.
 Acts as an inflammatory drug through indirect inhibition of TNF-a; it limits the thrombin-induced
inflammatory response and prevents the TNF-a production of monocytes.
 Also acts as a pro-fibrinolytic drug for it stops the plasminogen activation inhibitor or PAI-1.

OTHERS

 According to Karch (2011), there are no common side effects being reported when the medication is
ADVERSE EFFECTS properly administered.
 The most common adverse effect from the drug is the higher risk for bleeding.

CLINICALLY
IMPORTANT DRUG- Heparin for venous thromboembolism (VTE) prophylaxis may be coadministered with Xigris.
DRUG INTERACTIONS

NURSING CONSIDERATIONS

 The patient should be monitored very closely to take note of any sign of increased bleeding because there is no currently
available antidote for this drug.
 The medication should only be administered if the benefit outweighs the risks for the patient.

ANTIHEMOPHILIC FACTOR
ANTIHEMOPHILIC AGENTS
GENERIC NAME Antihemophilic factor

TRADE NAME Bioclate

IMAGE

Photo Reference: http://www.medicalook.com/reviews/Bioclate.html

This drug is a recombinant coagulation Factor VIII that is used to cure patients with hemophilia A, von Willebrand
INDICATIONS
disease, and Factor XIII deficiency.

DOSAGE & FORMS IV dose depending on the level of antihemophilic factor, weight, and patient response.

PHARMACOKINETICS

Absorption

Distribution

Metabolism

Excretion

 24 to 36 hours (Karch, 2011)

Half-life
 18.4 to 19.3 hours (DrugBank, 2021)

PHARMACODYNAMICS

Duration Unknown

Onset Immediate after administration

Peak Effects Unknown

 Antihemophilic agents have a protein present in plasma that is required for the development of clots.
Injected medication raises AHF plasma levels and can temporarily cure the coagulation deficiency in
Mechanism of
people with hemophilia A or also known as the classical hemophilia.
Action
 The Antihemophilic Factor combines and interacts with factor IXa, as well as calcium and phospholipid.
This compound transforms factor X to factor Xa, facilitating the clotting to occur.

Adverse effects of the drugs occur when the drug is associated with the use of blood products such as hepatitis
ADVERSE EFFECTS and AIDS. Adverse effects also include headache, flushing, lethargy, nausea and vomiting, stinging, itching, and
burning sensation at the injection site.

 Taking carfilzomib can result in a critical and serious blood clots on rare occasions, and taking it
alongside antihemophilic factors would enhance the risk. Age, cigarette smoking, high blood pressure,
and high cholesterol all raise the risk.
CLINICALLY  When emicizumab is administered together with an antihemophilic factor, the danger of blood clots
IMPORTANT DRUG- increases, which might lead to significant problems just like stroke, pulmonary embolism or pulmonary
DRUG INTERACTIONS artery blockage, heart attack, heart failure, collapse, and renal failure.
 Pegvaliase may cause severe allergic reactions when used with antihemophilic factors.

NURSING CONSIDERATIONS

 Assess of cautions and contraindications such as allergies to the drug and if the patient has any liver
disease.
 Assess the baseline profile and status of the patient before starting the treatment.
Assessment
 Assess the overall condition of the patient such as blood pressure, pulse rate, orientation and reflexes,
body temperature, akin color and presence of any skin lesions, respirations, clotting lab results, and
hepatic function examinations.
  Ineffective tissue perfusion related to coagulation.
 Acute pain related to gastrointestinal, central nervous system, or skin effects.
Diagnosis
 Anxiety or fear related to the diagnosis and use of blood related products.
 Deficient knowledge regarding the drug therapy.

 Make sure to administer the medication only via IV to guarantee effectiveness.

 Observe any clinical reaction or response such as clotting factor levels regularly to arrange and adjust
dosage.
 Observe for any signs of thrombosis.
 Lower the rate of infusion if the patient experiences side effects to avoid any severe drug reaction.
Implementation
 Prepare and arrange type and crossmatch blood for blood transfusions.
 Mark the chart of the patient to alert other medical staff that the patient is a potential risk for increased
bleeding.
 Provide health teachings to the patient.
 Offer support and encouragement to the patient.

 Observe the response of the patient to the medication.

 Closely monitor for any adverse effects.
Evaluation
 Evaluate the effectiveness of the teaching plan.
 Watch and monitor for the effectiveness of comfort measures and compliance with the drug therapy.

AMINOCAPROIC ACID
HEMOSTATIC AGENTS

GENERIC NAME aminocaproic acid

TRADE NAME Amicar

IMAGE

References:https://americanregent.com/our-products/aminocaproic-acid-injection-usp/ and
https://allmedtech.com/ambanagamacb.html

 Medication to treat excessive bleeding caused by hyperfibrinolysis and even utilized to avoid repetition of
INDICATIONS subarachnoid hemorrhage, to control megakaryocytic thrombocytopenia, to reduce the requirement for
platelet administration, and to prevent and cure hereditary angioneurotic edema episodes.

 IV and oral forms

DOSAGE & FORMS  5 mg either orally or intravenously, then 1-1.25 g/h
 Should not exceed 30 g in 24 hours.

PHARMACOKINETICS (Karch, 2011)

Absorption Rapidly absorbed in the body after administration.

Distribution Widely distributed throughout the body.

Metabolism 11% of the dose appears to be the metabolite adipic acid.

Excretion Excreted largely in urine (65%).

Half-life Has a half-life of 2 hours.

PHARMACODYNAMICS

 Oral: unknown
Duration
 IV: 2-3 hours

Onset  Oral: rapid

  IV: immediate

 Oral: 2 hours
Peak Effects
 IV: in a span of minutes

 Works as an antifibrinolytic; derivative of the amino acid lysine.

Mechanism of
Action  It suppresses plasminogen activator molecules and has antiplasmin action, which prevents fibrinolysis
and keeps clots from breaking down.

 The most known adverse effect of this systemic hemostatic agent is the possibility of having excessive
bleeding.
 CNS effects such as hallucinations, drowsiness, dizziness, headache, and psychotic states.
ADVERSE EFFECTS
 GI effects such as nausea, diarrhea, and cramps.
 Other bodily effects such as fatigue, malaise, and muscle pain.
 Intrarenal obstruction and renal dysfunction.

CLINICALLY
 Hypercoagulation can occur when this medication is combined with oral contraceptives or estrogen.
IMPORTANT DRUG-
DRUG INTERACTIONS  There is an elevated risk for bleeding if this medication is administered with heparin.

NURSING CONSIDERATIONS

 Assess if there are allergies to any components of the drug.

 Assess for acute DIC
Assessment  Assess if the patient has renal or hepatic dysfunction
 Assess for the baseline status of the patient such as body temperature, skin color, lesions, orientation
and reflexes, blood pressure, etc., and monitor for adverse effects.

 Disturbed sensory perception related to CNS effects.

 Acute pain related to GI, CNS, or muscle effects.
Diagnosis
 Risk for injury related to CNS or blood-clotting effects.
 Deficient knowledge regarding drug therapy.

 Observe the clinical response and clotting factor levels of the patient regularly.
 Observe if there are any signs of thrombosis.
 Enlighten the patient regarding the support and safety measures when adverse effects occur such as
Implementation
hallucinations.
 Provide family and patient health teaching regarding the drug therapy.
 Offer support and encouragement.

 Watch or monitor the response of the patient to the drug.

 Observe for any signs of adverse effects.
Evaluation
 Evaluate the effectiveness of the drug therapy.
 Observe the effectiveness of comfort provided to the patient.
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