Treatment of angina pectoris with cinchona alkaloids.

Reports indicating the value of quinidine sulfate in angina pectoris led to (1) a search for related drugs which were equally effective but less toxic, and (2) a study of the mode of action of these drugs. It was found that quinidine, quinine, cinchonadine, and cinchamidine decrease the frequency of attacks in daily life and increase the exercise tolerance as measured by a standardized test. Quinine sulfate (0.3 to 0.4 Gm. every eight hours) appears to be the drug of choice from the standpoint of availability and low toxicity as well as effectiveness. The value of these drugs is apparently due to a vasodilating action which in turn is dependent on the presence of the quinoline ring. P REVIOUS studies1-6 have demonstrated the value of quinidine sulfate in the treatment of some patients with angina pectoris. However, most general practitioners and, in fact, many cardiologists hesitate to use quinidine in angina because of the complications which occasionally follow its use in the treatment of cardiac arrhythmias. Furthermore , many physicians hesitate to use quinidine in angina pectoris because its mode of action in this condition is not clear. It seemed worthwhile , therefore, to study the activity of drugs related to quinidine in an attempt to find a substance equally effective but possibly less toxic and also to throw some light on the mechanism of action in the treatment of angina pectoris. The comparative value of 12 pharmaceutical preparations was investigated in patients with angina pectoris. Five of these 12 were cinchona alkaloids (the sulfate salts of quinidine, quinine, cinchonine, cinchonidine, and cinchamidine); these were studied to determine whether drugs which were similar to quinidine in chemical structure but different in cardiodynamic and cardiotoxic effects were of therapeutic value in angina. Procaine amide (Pronestyl) was included because, like quinidine, it is of value in eliminating ectopic ventricular beats. Three synthetic antimalarial preparations (chloro-quine, pentaquine and chlorguanide) were chosen to see whether the therapeutic action in angina might be related to the mechanism responsible for antimalarial activity. Nitro-glycerin was used to determine which patients were likely to be benefited by vasodilator drugs and also to compare the effectiveness of the cinchona alkaloids with that of nitroglycerin which is the most effective of the drugs for angina. Pentaerythritol tetranitrate (Peritrate) was included to compare the frequency and degree of response of the cinchona alkaloids with that of a preparation currently advocated for …