Drugs used in the treatment of congestive cardiac failure and angina pectoris

The reduced cardiac output seen in congestive cardiac failure is associated with regional vasoconstriction and fluid retention. By reducing the synthesis of angiotensin II the angiotensin-converting enzyme (ACE) inhibitors induce vasodilatation and reduce fluid overload. They not only alleviate the symptoms of heart failure but decrease mortality. Thiazides, loop diuretics and the aldosterone antagonist spironolactone are often used in combination with an ACE inhibitor in order to reduce fluid overload. Digoxin increases the force of cardiac contraction and hence increases cardiac output. However, while digoxin can alleviate the symptoms of heart failure it does not reduce mortality. The pain of angina pectoris is associated with an imbalance between the myocardial oxygen demand and the oxygen supply. Nitrovasodilators are prodrugs for which the active principle is nitric oxide. By causing dilatation of capacitance veins and arterioles, these agents reduce cardiac preload and afterload, respectively, thereby reducing cardiac oxygen demand. Nicorandil has an action similar to that of the nitrovasodilators but also opens ATP-sensitive K+ channels. Dihydropyridine inhibitors of Ca2+ influx reduce cardiac preload and afterload respectively by dilating capacitance veins and arterioles. Verapamil and diltiazem not only dilate arterioles but also directly depress the heart. The inhibitors of Ca2+ influx therefore alleviate angina by reducing myocardial oxygen demand. Antagonists at β-adrenoceptors reduce the stimulant effects of noradrenaline on cardiac force and rate. The reduction in heart rate improves coronary blood flow by increasing the duration of diastole. Antagonists at β-adrenoceptors may therefore alleviate angina not only reducing cardiac oxygen demand but also by improving the oxygen supply.