Cardiovascular Drugs

Functional Components
of the Heart
Myocardium: cardiac muscle fibers are arranged into
four chambers, 2 atria and 2 ventricles
Conduction system: specialized tissue that conducts
nerve impulses throughout the heart, SA and AV
node, bundle of His, bundle branches, and Purkinje
fibers
Nerve supply: nerve branches from both the
sympathetic and parasympathetic divisions of the
autonomic nervous system, regulate heart rate and
force of contraction
Structure of the Heart
Normal electrocardiogram at rest
Main Diseases of the
Cardiovascular System
Hypertension
Congestive heart failure
Coronary artery disease
Myocardial infarction
Cardiac arrhythmias
Congestive Heart Failure
Contractile function is reduced below normal by
disease or life style
Cardiac output unable to maintain normal blood
pressure
Blood accumulates in heart (dilatation), lungs
(pulmonary congestion), abdomen (ascites), and
lower extremities (peripheral edema)
Patient is weak and has difficulty breathing
Coronary Artery Disease
Due to arterio- and atherosclerosis of the
coronary arteries
Fatty plaques cause blockage and decreased
blood flow to the myocardium
Main symptom is angina pectoris or chest
pain, caused by lack of blood and oxygen
Myocardial infarction (MI) occurs when an
artery is totally blocked

Myocardial Infarction
Caused by complete blockage of one of the
coronary arteries
Heart cells deprived of blood/oxygen become
ischemic, die, and form an infarct
MI may result in sudden death, or the infarct
undergoes a healing process and is replaced with
connective tissue
After an MI the heart may be weakened and
develop congestive failure or cardiac arrhythmias


Cardiac Arrhythmias
Arrhythmias are disturbances in the normal
electrical activity of conduction system
The electrical disturbance interferes with
the ability of the heart to pump blood, and
may cause angina pectoris or congestive
heart failure
Severe arrhythmias can cause ventricular
fibrillation and sudden death
Use of ECG for Diagnosis (ST
depression)
Hypertension
Hypertension is the leading cause of
cardiovascular disease and mortality
Disease symptoms and organ damage
caused by hypertension are not evident until
1015 years after the disease has started
Proper medication and patient compliance
will control most cases of hypertension
Causes of Hypertension
Most people have essential hypertension where the
exact cause is not known
Increased sympathetic activity and sodium
overload increase blood pressure (BP)
Renal disease and increased renin-angiotensin-
aldosterone activity raise BP and cause sodium
and fluid retention
Smoking, body overweight, and increased sodium
consumption contribute to hypertension
Drug Classes Used to Treat
Hypertension
Diuretics
Sympatholytic drugs
Vasodilator drugs
Calcium antagonist drugs
Angiotensin-converting enzyme inhibitor and
angiotensin receptor blocking drugs
Diuretic Therapy
Diuretics increase sodium excretion and relax
arterial blood vessels (vasodilation)
Thiazides are preferred in patients with adequate
renal function
Organic acid diuretics (loop diuretics) are used in
patients with reduced renal function
Diuretics can be used alone or in combination with
other antihypertensive drugs
Excessive loss of fluid, sodium, and potassium are
common adverse effects
Sympathetic Blocking Drugs
Alpha blockers lower BP by vasodilation
Beta blockers lower BP by decreasing heart
rate and cardiac output
Centrally acting sympatholytic drugs
decrease the activity of the cardiovascular
centers in the medulla oblongata
Vasodilator Drugs
Vasodilators decrease the muscular tone and
contractile function of blood vessels
Hydralazine and minoxidil are potent
vasodilators that must be used with diuretics
and sympathetic blocking drugs
Minoxidil causes hirsutism and is sold
topically for treatment of baldness

Calcium Antagonists
Block the influx of calcium into the heart
and arterial blood vessels
Verapamil and diltiazem act on both the
heart and blood vessels to lower BP
Nifedipine and other calcium blockers
lower BP only by vasodilation
Calcium antagonists are also used to treat
angina pectoris and cardiac arrhythmias

Angiotensin-Converting Enzyme
Inhibitors (ACEIs)
ACEIs inhibit the formation of angiotensin which is a
potent vasoconstrictor
ACEIs decrease the release of aldosterone which
retains sodium and water
The ACEIs can be used with thiazide and organic
acid diuretics, but not potassium-sparing diuretics
These drugs produce a low incidence of adverse
effects and do not interfere with mental activity or
renal function
Angiotensin Receptor Blockers
These drugs block angiotensin receptors on
blood vessels and adrenal cortex
Like the ACEIs, these drugs produce
vasodilation and decrease the activity of
aldosterone
The angiotensin receptor blockers generally
produce a lower incidence of adverse
effects than the ACEIs

Treatment of
Hypertensive Crisis
Severe hypertension is a medical emergency
that can lead to stroke and sudden death
Immediate parenteral administration of
antihypertensive drugs can avoid severe
complications and irreversible damage
Diazoxide and nitroprusside are potent
vasodilators used in hypertensive crisis
Angina Pectoris
Chest pain due to coronary artery disease
(CAD) and myocardial ischemia
Exertional angina (pain) usually occurs
during physical exertion or stress
Vasospastic angina may occur at any time
and is due to coronary artery vasospasm
Untreated CAD and angina pectoris may
lead to myocardial infarction and death
Drugs Used to Treat CAD
Nitrites and nitrates
Beta adrenergic blocking drugs
Calcium antagonists, also referred
to as calcium channel blockers
Nitrites and Nitrates
Drugs stimulate the formation of nitric oxide, a
potent vasodilator of blood vessels
Vasodilation of veins and arteries decreases
cardiac work and cardiac oxygen consumption to
relieve the pain of myocardial ischemia
Nitrites and nitrates may cause a drop in blood
pressure and reflex tachycardia
These drugs can be used to treat acute attacks of
angina or to prevent anginal attacks
Drugs Used to Relieve Acute
Attacks of Angina
Amyl nitrite is administered by inhalation from
a glass ampule, it has a sudden onset and
duration of action of 510 minutes
Nitroglycerin is administered as sublingual
tablets which require a few minutes for onset
and may last 3045 minutes
Nitroglycerin may also be administered
intravenously in more severe cases
Drugs Used Prophylactically to
Prevent Angina Pectoris
Nitroglycerin can be administered as an
ointment, as extended release tablets or
capsules, or by transdermal patch
Isosorbide and pentaerythritol nitrates are
usually administered orally 34 times/day
depending on the frequency of anginal attacks
Adverse Effects of Nitrites and
Nitrates
Vasomotor flushing, dizziness, and
headache are common due to vasodilation
When administered for acute angina, the
sudden onset of vasodilation may cause
hypotension, fainting, and tachycardia
Patients should be seated when inhaling or
taking these drugs sublingually

Beta Adrenergic Blockers
Sympathetic beta receptor stimulation of the heart
increases heart rate, force of contraction, and
oxygen consumption
Blockade of beta receptors decreases cardiac work
and cardiac oxygen demand
Beta blockers are used prophylactically to prevent
angina and can be combined with other
antianginal drugs
Calcium Antagonists
Drugs block influx of calcium ions into the heart and
blood vessels to vasodilate and lower blood pressure,
cardiac work, and oxygen demand
Verapamil and diltiazem act on both the heart and
blood vessels
Nifedipine and other calcium antagonists act mainly
to dilate arterial blood vessels
Calcium antagonists are used prophylactically to
prevent angina
Adverse effects include excessive vasodilation,
hypotension, cutaneous flushing, and headache
Congestive Heart Failure (CHF)
CHF due to weakening of the contractile function
of the heart
Blood and fluid accumulate in the heart, lungs,
abdomen, and lower extremities
Decreased cardiac output and blood pressure are
unable to meet body requirements
Cardiovascular reflexes cause vasoconstriction,
tachycardia, and sodium and fluid retention which
try to maintain blood pressure, but usually fail
Cardiac Glycosides
Drugs originally obtained from plant source,
Digitalis purpurea and Digitalis lanata
Digoxin and digitoxin are the only cardiac
glycosides currently available
Main pharmacologic effect of cardiac glycosides
is to increase the contractile force of myocardial
contraction
Cardiac glycosides also decrease heart rate and
atrioventricular conduction

Mechanism of Action
Cardiac glycosides inhibit Na/K adenosine
triphosphatase, the sodium pump which causes
more Na to remain inside myocardial cells
Increased intracellular Na stimulates Na/Ca
exchange that brings more Ca inside heart cells to
increase the force of contraction
Cardiac glycosides also stimulate the vagus nerve
which decreases heart rate
Pharmacokinetics and Dosing
Digoxin is water soluble and eliminated mostly
unmetabolized by the urinary tract
Digitoxin is more lipid soluble, requires
metabolism, and has a longer half-life
In acute CHF, initial digitalization doses are
administered to rapidly attain effective therapeutic
concentration
Lower daily maintenance doses are then given to
maintain desired therapeutic concentrations

Electrolyte and Cardiac
Glycoside Interactions
Low serum potassium (K) levels hypokalemia
increase drug toxicity and can cause cardiac
arrhythmias
High serum potassium levels hyperkalemia
decrease the actions of the cardiac glycosides
Increased serum calcium levels hypercalcemia
can increase the actions and toxicity of the cardiac
glycosides
Adverse Effects
Common complaints include headache,
dizziness, nausea, and vomiting
Visual disturbances halo effect around
lights often signals overdosage
Bradycardia, ectopic beats, and a variety of
other cardiac arrhythmias can occur and can
be life-threatening
Diuretic Therapy of CHF
Diuretic drugs are used to eliminate excess
sodium and fluid retention
Elimination of excess fluid allows the heart
to function more efficiently
Diuretics can be administered with cardiac
glycosides and other drugs used to treat
CHF

Vasodilator Therapy of CHF
Vasodilator drugs relax and dilate blood
vessels
Vasodilation decreases peripheral
resistance, allows more efficient blood flow,
and usually increases cardiac output
Angiotensin-converting enzyme inhibitors
and angiotensin receptor blocking drugs are
particularly useful in CHF
Cardiac Arrhythmias
Arrhythmias are disturbances in the normal
electrical activity of the heart
Arrhythmias can be detected on a recording of the
electrocardiogram (ECG)
Supraventricular arrhythmias occur above the
ventricles in the atria, SA node, and AV node
Ventricular arrhythmias occur in the ventricles and
Purkinje fibers and are usually more serious and
life-threatening
Electrophysiological Properties
of the Heart
Excitability associated with membrane
depolarization and the influx of Na ions
Refractory period associated with repolarization
and the efflux of K ions
Automaticity ability of the SA and AV nodes to
initiate membrane depolarizations
Under conditions of hypoxia and excessive
sympathetic stimulation, the ventricles can also
demonstrate automaticity to cause ectopic beats or
PVCs
Quinidine and Procainamide
Classified as class 1 antiarrhythmic drugs
Possess local anesthetic activity and block the
influx of Na ions during depolarization
Main effects are to decrease excitability, slow
conduction, and prolong the refractory period
ECG: prolong the PR, QRS, and QT intervals
Used for both supraventricular and ventricular
arrhythmias
Lidocaine
Class 1 local anesthetic-type antiarrhythmic
used only for ventricular arrhythmias
Must be administered IV by infusion
The drug of choice in acute and emergency
ventricular arrhythmias
Main effect is to decrease automaticity
Mexiletine and tocainide are similar to
lidocaine and can be administered orally
Propranolol
Classified as a class 2 antiarrhythmic drug
Primarily blocks cardiac beta receptors to
slow heart rate, AV conduction, and
prolong the refractory period
ECG: mainly increases the PR interval
Used for both supraventricular and
ventricular arrhythmias
Amiodarone
Classified as a class 3 antiarrhythmic drug
Usually reserved for more serious
arrhythmias when other drugs have failed
Main effect is to prolong the refractory
period and increase the QT interval
Drug contains iodine and can interfere with
thyroid function
Verapamil and Diltiazem
Classified as class 4 antiarrhythmic drugs
Act by blocking calcium ions
Main effects are to decrease heart rate and
AV conduction, increase the PR interval
Mainly used to treat supraventricular
arrhythmias
May cause cardiac depression at higher
doses
Adenosine
Administered IV in emergency situations
Main action is to decrease AV conduction
and slow the heart rate
Used to treat acute supraventricular
tachycardia
Duration of action is 1530 seconds