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Cardiovascular Drugs. Functional Components of the Heart Myocardium: cardiac muscle fibers are arranged into four chambers, 2 atria and 2 ventricles Conduction.

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Presentation on theme: "Cardiovascular Drugs. Functional Components of the Heart Myocardium: cardiac muscle fibers are arranged into four chambers, 2 atria and 2 ventricles Conduction."— Presentation transcript:

1 Cardiovascular Drugs

2 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

3 Structure of the Heart

4 Normal electrocardiogram at rest

5 Main Diseases of the Cardiovascular System Hypertension Congestive heart failure Coronary artery disease Myocardial infarction Cardiac arrhythmias

6 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

7 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

8 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

9 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

10 Use of ECG for Diagnosis (ST depression)

11 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

12 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

13 Drug Classes Used to Treat Hypertension Diuretics Sympatholytic drugs Vasodilator drugs Calcium antagonist drugs Angiotensin-converting enzyme inhibitor and angiotensin receptor blocking drugs

14 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

15 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

16 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

17 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

18 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

19 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

20 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

21 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

22 Drugs Used to Treat CAD Nitrites and nitrates Beta adrenergic blocking drugs Calcium antagonists, also referred to as calcium channel blockers

23 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

24 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

25 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

26 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

27 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

28 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

29 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

30 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

31 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

32 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

33 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

34 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

35 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

36 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

37 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

38 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

39 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

40 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

41 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

42 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

43 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

44 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


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