Chapter 11: Antianginal Drugs

Antianginal Drugs establishes the pathophysiological basis of myocardial ischemia as an imbalance between oxygen supply and demand, distinguishing between stable angina (exertion-induced), unstable angina (pre-infarction), and variant or Prinzmetal angina (vasospasm-induced). The text details the mechanism of action for organic nitrates, such as nitroglycerin and isosorbide dinitrate, which function by releasing nitric oxide to activate guanylyl cyclase and increase cyclic GMP (cGMP); this pathway leads to vascular smooth muscle relaxation, preferentially affecting veins to decrease venous return (preload) and myocardial wall tension. The summary explains critical pharmacokinetic concepts including the first-pass effect, routes of administration from sublingual to transdermal, and the management of nitrate tolerance through dosing intervals. A significant portion of the chapter is dedicated to Calcium Channel Blockers (CCBs), differentiating between dihydropyridines like amlodipine and nifedipine, which primarily reduce arteriolar resistance (afterload), and non-dihydropyridines like verapamil and diltiazem, which also depress cardiac conduction and contractility by blocking L-type calcium channels. The role of beta-adrenergic antagonists (beta-blockers) is highlighted as a cornerstone for treating stable angina and improving post-myocardial infarction survival by reducing heart rate and contractility, though the text notes they are ineffective for vasospastic angina. Furthermore, the chapter introduces novel agents such as ranolazine, which inhibits the late inward sodium current to reduce intracellular calcium overload without altering hemodynamics, and ivabradine, which selectively blocks the funny current in the sinoatrial node to lower heart rate. The discussion concludes with therapeutic strategies for acute relief versus long-term prophylaxis, emphasizing the selection of drugs based on comorbidities like heart failure, asthma, and diabetes, while cautioning against specific drug interactions such as those between nitrates and phosphodiesterase inhibitors.