Cardiovascular Drugs

Functional Components of the HeartMyocardium: cardiac muscle fibers are arranged into four chambers, 2 atria and 2 ventriclesConduction 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 SystemHypertensionCongestive heart failureCoronary artery diseaseMyocardial infarctionCardiac arrhythmias

Congestive Heart FailureContractile function is reduced below normal by disease or life styleCardiac output unable to maintain normal blood pressureBlood accumulates in heart (dilatation), lungs (pulmonary congestion), abdomen (ascites), and lower extremities (peripheral edema)Patient is weak and has difficulty breathing

Coronary Artery DiseaseDue to arterio- and atherosclerosis of the coronary arteriesFatty plaques cause blockage and decreased blood flow to the myocardiumMain symptom is angina pectoris or chest pain, caused by lack of blood and oxygenMyocardial infarction (MI) occurs when an artery is totally blocked

Myocardial InfarctionCaused by complete blockage of one of the coronary arteriesHeart cells deprived of blood/oxygen become ischemic, die, and form an infarctMI 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 ArrhythmiasArrhythmias are disturbances in the normal electrical activity of conduction systemThe electrical disturbance interferes with the ability of the heart to pump blood, and may cause angina pectoris or congestive heart failureSevere arrhythmias can cause ventricular fibrillation and sudden death

Use of ECG for Diagnosis (ST depression)

HypertensionHypertension is the leading cause of cardiovascular disease and mortalityDisease symptoms and organ damage caused by hypertension are not evident until 1015 years after the disease has startedProper medication and patient compliance will control most cases of hypertension

Causes of HypertensionMost people have essential hypertension where the exact cause is not knownIncreased sympathetic activity and sodium overload increase blood pressure (BP)Renal disease and increased renin-angiotensin- aldosterone activity raise BP and cause sodium and fluid retentionSmoking, body overweight, and increased sodium consumption contribute to hypertension

Drug Classes Used to Treat HypertensionDiureticsSympatholytic drugsVasodilator drugsCalcium antagonist drugsAngiotensin-converting enzyme inhibitor and angiotensin receptor blocking drugs

Diuretic TherapyDiuretics increase sodium excretion and relax arterial blood vessels (vasodilation)Thiazides are preferred in patients with adequate renal functionOrganic acid diuretics (loop diuretics) are used in patients with reduced renal functionDiuretics can be used alone or in combination with other antihypertensive drugsExcessive loss of fluid, sodium, and potassium are common adverse effects

Sympathetic Blocking DrugsAlpha blockers lower BP by vasodilationBeta blockers lower BP by decreasing heart rate and cardiac outputCentrally acting sympatholytic drugs decrease the activity of the cardiovascular centers in the medulla oblongata

Vasodilator DrugsVasodilators decrease the muscular tone and contractile function of blood vesselsHydralazine and minoxidil are potent vasodilators that must be used with diuretics and sympathetic blocking drugsMinoxidil causes hirsutism and is sold topically for treatment of baldness

Calcium AntagonistsBlock the influx of calcium into the heart and arterial blood vessels Verapamil and diltiazem act on both the heart and blood vessels to lower BPNifedipine and other calcium blockers lower BP only by vasodilationCalcium 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 waterThe 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 BlockersThese drugs block angiotensin receptors on blood vessels and adrenal cortexLike the ACEIs, these drugs produce vasodilation and decrease the activity of aldosteroneThe angiotensin receptor blockers generally produce a lower incidence of adverse effects than the ACEIs

Treatment of Hypertensive CrisisSevere hypertension is a medical emergency that can lead to stroke and sudden deathImmediate parenteral administration of antihypertensive drugs can avoid severe complications and irreversible damageDiazoxide and nitroprusside are potent vasodilators used in hypertensive crisis

Angina PectorisChest pain due to coronary artery disease (CAD) and myocardial ischemiaExertional 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 CADNitrites and nitratesBeta adrenergic blocking drugsCalcium antagonists, also referred to as calcium channel blockers

Nitrites and NitratesDrugs stimulate the formation of nitric oxide, a potent vasodilator of blood vesselsVasodilation of veins and arteries decreases cardiac work and cardiac oxygen consumption to relieve the pain of myocardial ischemiaNitrites and nitrates may cause a drop in blood pressure and reflex tachycardiaThese 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 minutesNitroglycerin is administered as sublingual tablets which require a few minutes for onset and may last 3045 minutesNitroglycerin may also be administered intravenously in more severe cases

Drugs Used Prophylactically to Prevent Angina PectorisNitroglycerin can be administered as an ointment, as extended release tablets or capsules, or by transdermal patchIsosorbide and pentaerythritol nitrates are usually administered orally 34 times/day depending on the frequency of anginal attacks

Adverse Effects of Nitrites and NitratesVasomotor flushing, dizziness, and headache are common due to vasodilation When administered for acute angina, the sudden onset of vasodilation may cause hypotension, fainting, and tachycardiaPatients should be seated when inhaling or taking these drugs sublingually

Beta Adrenergic BlockersSympathetic beta receptor stimulation of the heart increases heart rate, force of contraction, and oxygen consumptionBlockade of beta receptors decreases cardiac work and cardiac oxygen demandBeta blockers are used prophylactically to prevent angina and can be combined with other antianginal drugs

Calcium AntagonistsDrugs block influx of calcium ions into the heart and blood vessels to vasodilate and lower blood pressure, cardiac work, and oxygen demandVerapamil and diltiazem act on both the heart and blood vesselsNifedipine and other calcium antagonists act mainly to dilate arterial blood vesselsCalcium 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 extremitiesDecreased 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 GlycosidesDrugs originally obtained from plant source, Digitalis purpurea and Digitalis lanataDigoxin and digitoxin are the only cardiac glycosides currently availableMain 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 ActionCardiac glycosides inhibit Na/K adenosine triphosphatase, the sodium pump which causes more Na to remain inside myocardial cellsIncreased intracellular Na stimulates Na/Ca exchange that brings more Ca inside heart cells to increase the force of contractionCardiac glycosides also stimulate the vagus nerve which decreases heart rate

Pharmacokinetics and DosingDigoxin is water soluble and eliminated mostly unmetabolized by the urinary tractDigitoxin is more lipid soluble, requires metabolism, and has a longer half-lifeIn acute CHF, initial digitalization doses are administered to rapidly attain effective therapeutic concentrationLower daily maintenance doses are then given to maintain desired therapeutic concentrations

Electrolyte and Cardiac Glycoside InteractionsLow serum potassium (K) levels hypokalemia increase drug toxicity and can cause cardiac arrhythmiasHigh serum potassium levels hyperkalemia decrease the actions of the cardiac glycosidesIncreased serum calcium levels hypercalcemia can increase the actions and toxicity of the cardiac glycosides

Adverse EffectsCommon complaints include headache, dizziness, nausea, and vomiting Visual disturbances halo effect around lights often signals overdosageBradycardia, ectopic beats, and a variety of other cardiac arrhythmias can occur and can be life-threatening

Diuretic Therapy of CHFDiuretic drugs are used to eliminate excess sodium and fluid retentionElimination of excess fluid allows the heart to function more efficientlyDiuretics can be administered with cardiac glycosides and other drugs used to treat CHF

Vasodilator Therapy of CHFVasodilator drugs relax and dilate blood vesselsVasodilation decreases peripheral resistance, allows more efficient blood flow, and usually increases cardiac outputAngiotensin-converting enzyme inhibitors and angiotensin receptor blocking drugs are particularly useful in CHF

Cardiac ArrhythmiasArrhythmias are disturbances in the normal electrical activity of the heartArrhythmias can be detected on a recording of the electrocardiogram (ECG)Supraventricular arrhythmias occur above the ventricles in the atria, SA node, and AV nodeVentricular arrhythmias occur in the ventricles and Purkinje fibers and are usually more serious and life-threatening

Electrophysiological Properties of the HeartExcitability associated with membrane depolarization and the influx of Na ionsRefractory period associated with repolarization and the efflux of K ionsAutomaticity ability of the SA and AV nodes to initiate membrane depolarizationsUnder conditions of hypoxia and excessive sympathetic stimulation, the ventricles can also demonstrate automaticity to cause ectopic beats or PVCs

Quinidine and ProcainamideClassified as class 1 antiarrhythmic drugsPossess local anesthetic activity and block the influx of Na ions during depolarizationMain effects are to decrease excitability, slow conduction, and prolong the refractory periodECG: prolong the PR, QRS, and QT intervalsUsed for both supraventricular and ventricular arrhythmias

LidocaineClass 1 local anesthetic-type antiarrhythmic used only for ventricular arrhythmiasMust be administered IV by infusionThe drug of choice in acute and emergency ventricular arrhythmiasMain effect is to decrease automaticityMexiletine and tocainide are similar to lidocaine and can be administered orally

PropranololClassified as a class 2 antiarrhythmic drugPrimarily blocks cardiac beta receptors to slow heart rate, AV conduction, and prolong the refractory periodECG: mainly increases the PR intervalUsed for both supraventricular and ventricular arrhythmias

AmiodaroneClassified as a class 3 antiarrhythmic drugUsually reserved for more serious arrhythmias when other drugs have failedMain effect is to prolong the refractory period and increase the QT intervalDrug contains iodine and can interfere with thyroid function

Verapamil and DiltiazemClassified as class 4 antiarrhythmic drugsAct by blocking calcium ionsMain effects are to decrease heart rate and AV conduction, increase the PR intervalMainly used to treat supraventricular arrhythmiasMay cause cardiac depression at higher doses

AdenosineAdministered IV in emergency situationsMain action is to decrease AV conduction and slow the heart rateUsed to treat acute supraventricular tachycardia Duration of action is 1530 seconds