Transcript Cardiovascular

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
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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
10–15 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-angiotensinaldosterone 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
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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 5–10 minutes
• Nitroglycerin is administered as sublingual
tablets which require a few minutes for onset
and may last 30–45 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 3–4 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 15–30 seconds