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