Angina pectoris antagonists

Dihydropyridines not only are intermediates for the synthesis of pyridines, but also are themselves an important class of N-heterocycles an example is the coenzyme NADH. Studies on the function of NADH led to increased interest in the synthesis of dihydropyridines as model compounds. Aryl-substituted dihy-dropyridines have been shown to be physiologically active as calcium antagonists. Some derivatives have found application in the therapy of high blood pressure and angina pectoris. For that reason the synthesis of 1,4-dihydropyridines has been the subject of intensive research and industrial use. The Hantzsch synthesis has thus become an important reaction. 

Fig. 4. Schematic presentation of the mechanism of calcium antagonists with respect to their beneficial effect in angina pectoris. The final result is an improvement of the imbalance between myocardial oxygen demand and supply. TPR = total peripheral resistance HR = heart rate.

Because of these interindividual variations in the kinetics of propranolol, the therapeutic dose of this drug is best determined by titration. End points of titration include relief of anginal symptoms, increases in exercise tolerance, and plasma concentration of propranolol between 15 and 100 ng/mL. For additional details on the pharmacokinetics of propranolol and other (3-receptor antagonists approved for clinical use in the treatment of angina pectoris, see Table 17.3 and Chapter 11. 

Beta-adrenoceptor antagonists are used to treat hypertension, angina pectoris, arrhythmias and secondary myocardial infarct prevention following primary infarction (timolol, metoprolol and propranolol). 

Beta antagonists are generally administered for their effect on the beta-1 receptors that are located on the heart.31 When stimulated, these receptors mediate an increase in cardiac contractility and rate of contraction. By blocking these receptors, beta antagonists reduce the rate and force of myocardial contractions. Consequently, beta antagonists are frequently used to decrease cardiac workload in conditions such as hypertension and certain types of angina pectoris. Beta blockers may also be used to normalize heart rate in certain forms of cardiac arrhythmias. Specific clinical applications of individual beta blockers are summarized in Table 20-2. 

Alpha-adrenergic antagonists are used primarily as antihypertensive drugs because of their ability to block vascular alpha-1 receptors. Beta-adrenergic antagonists (beta blockers) are administered primarily for their inhibitory effects on myocardial function and are used in the prevention and treatment of hypertension, angina pectoris, arrhythmias, and myocardial reinfarction. Many of the drugs introduced in this chapter are discussed further in chapters that deal with the specific clinical conditions (e.g., hypertension, asthma, and other disorders). 

Kumar S, Hall RJ. Drug treatment of stable angina pectoris in the elderly defining the place of calcium channel antagonists. Drugs Aging. 2003 20 805-815. 

Calcium antagonists can cause serious toxicity or death with relatively small overdoses. These channel blockers depress sinus node automaticity and slow AV node conduction (see Chapter 12 Vasodilators the Treatment of Angina Pectoris). They also reduce cardiac output and blood pressure. Serious hypotension is mainly seen with nifedipine and related dihydropyridines, but in severe overdose all of the listed cardiovascular effects can occur with any of the calcium channel blockers. 

Calcium antagonists L-type calcium channel blocker, decreases Angina pectoris. Side effects include... 

Braun S, van der Wall EE, Emanuelsson H, Kobrin I. Effects of a new calcium antagonist, mibefradil (Ro 40-5967), on silent ischemia in patients with stable chronic angina pectoris a multicenter placebo-controlled study. The Mibefradil International Study Group. J Am Coll Cardiol 1996 27(2) 317-22. 

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