The close chemical relationship between glyceryl trinitrate and erythrol tetranitrate suggests that these 2 drugs, despite clinical evidence to the contrary, should be equally effective in preventing attacks of angina pectoris. This proved to be true when the drugs were administered by the same route. Thus, erythrol tetranitrate when administered sublingually (instead of being swallowed, as is the custom) behaves like nitroglycerin and is one of the most effective vasodilators available. Conversely, nitroglycerin when swallowed (instead of being taken sublingually, as is the custom) is ineffective and erratic in activity. A similar striking increase in vasodilating action on sublingual administration is seen also with mannitol hexanitrate and triethanolamine trinitrate and to a lesser extent with pentaerythritol tetranitrate but not with sodium nitrite.The prolonged effect of erythrol tetranitrate, when administered sublingually or in the buccal pouch, makes it particularly valuable in the clinical management of patients with angina pectoris.
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
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