Summary

Recognition of phenytoin’s basic property, stabilization of bioelectrical activity, led to its therapeutic use in cardiology. The first evidence was provided by Harris and Kokernot in 1950 in a basic mechanism study showing that PHT reversed cardiac arrhythmias after coronary occlusion in dogs. The first evidence of its clinical usefulness in cardiac arrhythmias in man was presented, in a detailed paper, by Leonard in 1958.

Subsequent studies have shown that PHT is useful in a wide range of cardiovascular disorders. It is effective in the treatment of a variety of cardiac arrhythmias, including ventricular arrhythmias associated with hypokalemia, digitalis toxicity, ischemia and myocardial infarction, surgical procedures and myopathic processes; paroxysmal atrial tachycardia and atrial extrasystoles; and as prophylaxis against anesthesiaand cardioversion-induced arrhythmias.1 PHT’s ability to offset the toxic effects of digitalis without impairing its inotropic benefits allows larger amounts of digitalis to be given before toxic levels are reached.

PHT has been shown to have beneficial effects on the cardiac conduction system. These effects are an example of PHT’s biphasic actions since, dependent on the initial state of the tissue, it can either increase or decrease conduction. PHT does not alter normal sinus node function or rate, atrial refractoriness, intra-atrial conduction velocity, or prolong Q-T interval. PHT has been found beneficial in the treatment of the prolonged Q-T interval syndrome, torsade de pointes arrhythmias and tricyclic antidepressant induced arrhythmias.

PHT has been shown to decrease sympathetic nervous system activity with resultant reduction in cardiac contractile force, blood pressure and heart rate. It has been reported to be useful in hypertension.3

Both clinical and laboratory studies have shown PHT to be useful in hypoxic-ischemic states. Clinically, PHT has been reported to reduce the frequency and severity of anginal attacks,4 improving ST depression on the electrocardiogram. It controls ischemia-induced arrhythmias; and improves brain function in ischemic states, including reduction of neurological deficits after cardiac arrest.5 In the laboratory, PHT has been demonstrated to increase cerebral and cardiac blood flow and to have anti-anoxic and anti-ischemic effects in brain, nerve, heart and lung.

PHT has been reported to increase high-density lipoprotein-cholesterol (HDL-C) levels. Since there is evidence that there is an inverse relationship between HDL-C levels and atherosclerotic problems such as myocardial infarction and stroke, the use of PHT as a preventive against these disorders is suggested.6

In addition to its specific cardiovascular actions, PHT has general properties relevant to the treatment of cardiovascular disorders. These include its usefulness against pain, anxiety, fear, anger and stress, without sedative effect.

1. Cardiac arrhythmias (various): Refs. 18, 61, 141, 166, 187, 221, 248, 310, 418, 517, 720, 721, 753, 987, 1052, 1121, 1214, 1264, 1339, 1390, 1488, 1847, 2058, 2083, 2251, 2331, 2390, 2528, 2569. Cardioversion-induced arrhythmias: Refs. 248, 720, 923, 936, 1264, 1289. Arrhythmias associated with myocardial infarction: Refs. 221,248,516, 987,1120,1705, 2150, 2151, 2478, 2649, 2650, 2729.
2. Conduction defects: Refs. 22, 154, 158, 327, 753, 764, 816, 826, 830, 831, 832, 833, 884, 935, 1114, 1120, 1390, 1434, 1450, 1488, 1562, 1645, 1776, 1804, 1822, 2069, 2163, 2223, 2296, 2348, 2361, 2376, 2377, 2478, 2558, 2565, 2664, 2695, 2799, 2883, 2992, 3037, 3052, 3066. Prolonged Q-T interval: Refs. 764, 1776, 1972, 2069, 2071, 2094, 2223, 2328, 2361, 2370, 2376, 2462, 2558, 2695, 2807, 2837, 2895, 2951, 2957, 3066. Torsade de pointes: Refs. 158, 764, 816, 935, 2069, 2296, 2478, 2664, 2799, 2883, 2992, 3052. Tricyclic antidepressant overdose: Refs. 2348, 2377, 2565.
3. Hypertension: Refs. 414, 1480, 1717, 1797, 2090, 2316, 2668.
4. Angina pectoris: Refs. 18, 1611, 2667.
5. Cerebrovascular insufficiencies: Refs. 938, 1216, 1560, 1718, 1719, 2142, 2768. See also Anti-anoxic Effects of PHT.
6. High-density lipoproteins (HDL): Refs. 1893, 1961, 2002, 2162, 2235, 2318, 2319, 2323, 2428, 2542, 2649, 2650, 2652, 2734, 2741, 2813, 2814, 2827, 2897, 2946.
7. See also Thought, Mood and Behavior section—beneficial effects of PHT on fear, anxiety, anger and stress; and Pain section.

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