Anti-Toxic Effects of PHT

The toxic effects of many substances, both in man and in the laboratory, have been reported to be diminished or counteracted by PHT. The substances listed here are those with particular clinical relevance. Some are poisons; others are therapeutic but can have toxic effects, especially in overdose.

For Alcohol withdrawal: Refs.

383. Wilhoit, W. M. C., The broader treatment of acute alcoholism and delirium tremens, J. Florida Med. Assn., 52: 254-255, 1965.
571. Chafetz, M. E., Alcohol withdrawal and seizures, JAMA, 200: 195-196, 1967.
2141. Adams, H.P., Diphenylhydantoin in the treatment of alcohol withdrawal, JAMA, 218(4): 598, 1971
2182. Finer, M.J., Diphenylhydantoin for treatment of alcohol withdrawal syndromes, JAMA, 215(1): 119, 1971.

Lab. study: Ref.

2977. Sprague, G. L., Craigmill, A. L., Control of ethanol withdrawal symptoms in mice by phenytoin, Res. Commun. Chem. Pathol. Pharmacol., 15: 721-31, 1976.

Alloxan induced diabetes: Lab. studies: Refs.

1015. Esposito-Avelia, M. and Mennear, J. H., Studies on the protective effect of diphenylhydantoin against alloxan diabetes in mice, Proc. Soc. Exp. Biol. Med., 142: 82-85, 1973.
1092. Gossel, T. A. and Mennear, J. H., Inhibition of alloxan-induced diabetes by diphenylhydantoin sodium, Pharmacologist, 13:238, 1971.
1354. Mennear, J. H. and Gossel, T. A., Inhibitory effect of diphenylhydantoin on the diabetogenic action of alloxan in the mouse, Diabetes, 21: 80-83, 1972.

Amphetamine toxicity: Ref.

1904. Ifabumuyi, O. I. and Jeffries, J. J., Treatment of drug-induced psychosis with diphenylhydantoin, Can. Psychiatr. Assoc. 21: 565-9, 1976.

Lab. study: Ref.

99. Fink, G. B. and Swinyard, E. A., Comparison of anticonvulsant and psychopharmacologic drugs, J. Pharm. Sci., 51: 548-551, 1962.

Antidepressants (tricyclies, e.g., amitriptyline, imipramine) induced arrhythymias and conduction defects: Refs.

1382. Newtown, R., Amitriptyline and imipramine poisoning in children, Brit. Med. J., 2: 176, 1974.
1428. Postlethwaite, R. J. and Price, D. A., Amitriptyline and imiprarnine poisoning in children, Brit. Med. J., 2: 504, 1974.
1430. Price, D. A. and Postiethwaite, J. R., Amitriptyline and imipramine poisoning in children, Brit. Med. J., 1: 575, 1974.
2257. Stannard, M. and Caplan, H. L., Cardiac arrest due to imipramine hydrochloride, Med. J. Aust., 2(1): 22-4, 1967.
2348. Boehnert, M., Lovejoy, F. H., The effect of phenytoin on cardiac conduction and ventricular arrhythmias in acute tricyclic antidepressant (TCA) overdose, Vet. Hum. Toxicol., 27: 297, Abst. 32, 1985.
2377. Cantrill, V., Prophylactic phenytoin in tricyclic overdose, J. Emerg. Med., 1: 169-77, 1983.
2565. Hagerman, G. A., Hanashiro, P. K., Reversal of tricyclic-antidepressant-induced cardiac conduction abnormalities by phenytoin, Ann. Emerg. Med., 10(2): 82-6, 1981.
2674. Kulig, K., Baror, D., Marx, J., Wythe, E., Rumack, B. H., Phenytoin as treatment for tricyclic antidepressant cardiotoxicity in a canine model, Vet. Hum. Toxicol., 26(5): A-2, 1984.
2675. Kulig, K., Baror, D., Marx, J., Wythe, E., Rumack, B. H., Phenytoin as treatment of the cardiotoxicity of tricyclic antidepressant overdose in experimental animals, Vet. Hum. Toxicol., 25: 285, 1983.
2764. Marshall, J. B., Forker, A. D., Cardiovascular effects of tricyclic antidepressant drugs: therapeutic usage, overdose, and management of complications, Am. Heart J., 103 (3): 401-14, 1982
2830. Nissimov, B., Weiss, S., Zaavi, I., Mozes, K., Cardiac arrhythmias and electrocardiographic abnormalities in amitriptyline poisoning, Harefuah, 105-8 142-43, 1981

Lab. studies: Refs.

674. Kulig, K., Baror, D., Marx, J., Wythe, E., Rumack, B. H., Phenytoin as treatment for tricyclic antidepressant cardiotoxicity in a canine model, Vet. Hum. Toxicol., 26(5): A-2, 1984.
2675. Kulig, K., Baror, D., Marx, J., Wythe, E., Rumack, B. H., Phenytoin as treatment of the cardiotoxicity of tricyclic antidepressant overdose in experimental animals, Vet. Hum. Toxicol., 25: 285, 1983
2778. Mayron, R., Ruiz, E., Phenytoin: does it reverse tricyclic-antidepressant-induced cardiac conduction abnormalities?, Ann. Emerg. Med., 14(5): 505, 1985.

Bilirubin toxicity in newborns: Refs.

1388. O’Leary, J. A., Feldman, M., and Switzer, H. E., Phenobarbital-Dilantin treatment of the intrauterine patient, J. Reprod. Med., 5: 81-83, 1970.
1926. Koch, M. M., Lorenzini, I., Freddara, U., Jezequel, A. M. and Orlandi, F., Type 2 Crigler-Najjar syndrome. Quantitation of ultrastructural data and evolution under therapy with phenytoin, Gastroenterol. Clin. Biol., 2: 831-42, 1978.
2465. Drew, J. H., Kitchen, W. H., The effect of maternally administered drugs on bilirubin concentrations in the newborn infant, J. Pediatr., 89(4): 657-61, 1976.

Carbamazepine induced water intoxication: Refs.

2020. Perucca, E. and Richens, A., Water intoxication produced by carbamazepine and its reversal by phenytoin, Br. J. Clin. Pharmacol., 9: 302-4P, 1980.
2089. Sordillo, P., Sagransky, D. M., Mercado, R. and Michelis, M. F., Carbamazepine-induced syndrome of inappropriate antidiuretic hormone secretion--reversal by concomitant phenytoin therapy, Arch. Intern. Med., 138: 299-301, 1978
2640. Kalff, R., Houtkooper, M. A., Meyer, J. W., Goedhart, D. M., Augusteijn, R., Meinardi, H., Carbamazepine and serum sodium levels, Epilepsia, 25(3): 390-7, 1984.

Chloral hydrate induced cardiac arrhythmias: Ref.

1873. Gustafson, A., Svensson, S. E. and Ugander, L., Cardiac arrhythmias in chloral hydrate poisoning, Acta Med. Scand., 201: 227-30, 1977.

Clofibrate induced myotonic states: Lab. study: Ref.

2682. Kwiecinski, U., Myotonia induced with clofibrate in rats, J. Neurol., 219: 107-16, 1978.

Cyanide toxicity in nerve: Lab. studies: Refs.

699. Pincus, J. H., Grove, I., Marino, B. B., and Glaser, G. E., Studies on the mechanism of action of diphenylhydantoin, Arch. Neurol., 22: 566-571, 1970.
812. Becker, B. and Podos, S. M., Diphenylhydantoin and its use in optic nerve disease, Symposium an Ocular Therapy, Vol. VI, I. H. Leopold, Ed., C. V. Mosby Co., St. Louis, 1973.

Digitalis and other cardiac glycoside induced arrhythmias. Use of PHT permits more digitalis to be used before toxic effects occur and does not interfere with the ino-tropic benefits of digitalis in animals and humans: Refs.

61. Conn, R. D., Diphenylhydantoin sodium in cardiac arrhythmias, New Eng, J. Med., 272: 277-282, 1965.
62. Conn., R. D., New drugs for old hearts: newer antiarrhythmic and diuretic agents, Postgrad. Med. 42: 71-79, 1967.
80. Dorph, M., Coronary care units and the aggressive management of acute myocardial infarction, Delaware Med. J. 44-48, February, 1968.
82. Dreifus, L. S., Rabbino, M. D., and Watanabe, V., Newer agents in the treatment of cardiac arrythmias, Med. Clin. N. Amer., 48: 371-387, 1964.
158. Helfant, R. H., Lau, S. H., Cohen, S. I., and Damato, A. N., Effects of diphenylhydantoin on atrioventricular conduction in man, Circulation, 36: 686-691, 1967.
187. Karliner, J. S., Intravenous diphenylhydantoin sodium (Dilantin) in cardiac arrhythmias, Dis. Chest, 51: 256-269, 1967.
215. Lang, T. W., Bernstein, H., Barbieri, F. F., Gold, H. and Corday, E., Digitalis toxicity: treatment with diphenylhydantoin, Arch. Intern. Med., 116: 573-580, 1965.
248. Mercer, E. N. and Osborne, J. A., The current status of diphenylhydantoin in heart disease, Ann. Intern. Med., 67: 1084-1107, 1967.
310. Rosen, M., Lisak, R., and Rubin, I. L., Diphenylhydantoin in cardiac arrhythmias, Amer. J. Cardiol., 20: 674-678, 1967.
318. Ruthen, G. C., Antiarrhythmic drugs: Part IV. Diphenylhydantoin in cardiac arrhythmias, Amer. Heart J., 70: 275-278, 1965.
407. Wehrmacher, W. H., Dilantin in the management of cardi4c arrhythmias, Curr. Med. Dig., 36: 45-49, 1969.
415. Conn, R. D., Newer drugs in the treatment of cardiac arrhythmia, Mod. Clin. N. Amer., 51: 1223-1240, 1967.
418. Bashour, F. A., Edmondson, R. E., Gupta, D. N., and Prati, R., Treatment of digitalis toxicity by diphenylhydantoin (Dilantin), Dis. Chest, 53: 263-270, 1968.
597. Bigger, T. J., Jr., Schmidt, D. H., and Kutt, H., Relationship between the plasma level of diphenythydantoin sodium and its cardiac antiarrhythmic effects, Circulation, 38: 363-374, 1968.
753. Adamska-Dyniewska, H., The effect of diphenylhydantoin sodium given with cardiac glycosides on the left ventricular systole dynamics, Pol. Med. J., 9: 304-308, 1970.
754. Adamska-Dyniewska, H., The value of diphenylhydantoin for combating the rhythm and conduction disorders induced by cardiac glycosides, Biul. Wojskewej. Akad. Medy., 14: 7 1 77, 1971.
832. Bissett, J. K., Kane, J. J., desoyza, N., and Doherty, J., Effect of diphenylhydantoin on bundle branch block in man, Clin. Res., 21: 405, 1973.880. Burckhardt, D. and Sefidpar, M., Digitalis intoxication: contribution to diagnosis and therapy, Schweiz. Rundschau. Med. (Praxis), 60: 1705-1711, 1971.
905. Chung, E. K., The current status of digitalis therapy, Modern Treatment, 8: 643-714, 1971.
941. Danzig, R., Treatment of arrhythmias associated with acute myocardial infarction, Nebraska Med. J., 56: 474-475, 1971.
969. Doherty, 1. E., Digitalis glycosides. Pharmacokinetics and their clinical implications, Ann. Intem. Med., 79: 229-238, 1973.
991. Editor, Diphenylhydantoin for digitalis toxicity, Postgrad. Med., 45: 244-245, 1969.
1007. Ellis, J. G. and Dimond, E. G., Newer concepts of digitalis, Amer. J. Cardiol., 17: 759-767, 1966.
1052. Gattenlohner, W. and Schneider, K. W., The effect of diphenylhydantoin on hemodynamics, Munchen Med.. Wschr., 11: 2561-2566, 1969.
1084. Goldstein, F. J., Continuing education via pharmatapes: Digitalis I. A basic pharmacological review, Amer. J. Pharm., 145: 135-141, 1973.
1114. Haiat, R., Chapelle, M., Benaim, R., Witchitz, S., and Chiche, P., Disappearance of an intraventricular conduction disorder under diphenylhydantoin, Sem. Hop. Paris, 47: 2957-2964, 1971.
1121. Hansen, H. W. and Wagener, H. H., Diphenylhydantoin in the treatment of heart failure, Deutsch. Med. Wschr., 96: 1866-1873, 1971.
1122. Hansen, H. W. and Wagener, H. H., Experimental studies an the influence of diphenylhydantoin glycoside effects on the heart, Herz Kreislauf Zeitschrift Fur Kardiologie und Angiologie in Klinik und Praxis, 6: 69-72, 1974.
1151. Hobson, J. D. and Zettner, A., Digoxin serum half-life following suicidal digoxin poisoning, JAMA, 223: 147-149, 1973.
1170. Huffman, D. H. and Azarnoff, D. L., The use of digitalis, Ration. Drug Ther., 8: 1-7, 1974.
1209. Kaufmann, G. and Hauser, K., Experience with diphenylhydantoin (antisacer) in the treatment of cardiac arrhythmias, Schweiz. Med. Wschr., 98: 1223-1226, 1968.
1214. Kemp, G. L., Treatment of ventricular ectopic rhythms with diphenylhydantoin, J. Amer. Geriat. Soc., 20: 265-267, 1972.
1264. Lesbre, J. P., Cathala, B., Salvador, M., Florio, R. Lescure, F., and Meriel, P., Diphenylhydantoin and digitalis toxicity, Arch. Mal. Coeur., 62: 412-437, 1969.
1289. Linde, L. M., Turner, S. W., and Awa, S., Present status and treatment of paroxysmal supraventricular tachycardia, Pediatrics, 50: 127-130, 1972.
1402. Patton, R. D., and Helfant, R. H., Atrial flutter with one-to-one conduction, Dis. Chest, 55: 250-251, 1969.
1434. Quiret, J. C., Bens, J. L., Duboisset, M., Lesbre, P. and Bernasconi, P., Diphenylhydantoin injectable in cardiology, Arch. Mal. Coeur., 67: 87-96, 1974.
1488. Rumack, B. H., Wolfe, R. R. and Gilfrich, H., Phenytoin (diphenylhydantoin) treatment of massive digoxin overdose, Brit. Heart J., 36: 405-408, 1974.
1508. Schick, D. and Scheuer, J., Current concepts of therapy with digitalis glycosides, Part II., Amer. Heart J., 87: 391-396, 1974.
1515. Schwender, C. F., Antiarrhythrnic agents, Annual Re ports in Medicinal Chemistry, 1970, 80-87, Cain, C. K., Ed., Academic Press, New York, 1971.
1562. Smith, T. W. and Haber, E., Digitalis, New Eng. J. Med., 289: 1125-1129, 1973.
1563. Smith, T. W., Digitalis glycosides, New Eng J. Med., 288: 942-946, 1973.
1590. Stazi, C. and Marasa, G., Arrhythmias due to digitalis and their treatment, Ann. Med. Nov. (Roma), 77: 51-80, 1972.
1705. Yang, C. P., Persistent ventricular tachycardia. The use of diphenylhydantoin, J. Kansas Med. Soc., 74: 418-421, 1973.
1707. Yasky, J., Moretti, O., Caroselia, C., Phenytoin treatment of cardiac arrhythmias induced by digitalis, Revista Argentina de Cardiologia, 41: 53-61, 1973.
1889. Heesen, H. and Lahrtz, H., Treatment of severe digitalis intoxication in suicidal attempt, Med. Klin., 70: 812-6, 1975.
2083. Sirohiya, M. K., Bhatnagar, H. N. S., Shah, D. R. and Narang, N. K., Phenytoin sodium in cardiac arrhythrnias, J. Indian Med. Assoc., 64(12): 329-34, 1975
2163. Chung, D.C., Anaesthetic problems associated with the treatment of cardiovascular disease: I. Digitalis toxicity, Can. Anaesth. Soc. J., 28(l): 6-16, 1981.
2331. Bielak, J., Pokora, J., The effect of hydantoinal on cardiac arrhythmias, Pol. Tyg. Lek., 25: 967-9, 1970.
2393. Chung, E. K., Unusual form of digitalis-induced triple A-V nodal rhythm, Am. Heart. J., 79(2): 250-53, 1970.
2569. Hansen, H. W., The treatment of digitalis induced cardiac arrhythmia with diphenylhydantoin, Med. Klin., 65: 101-4, 1970.
2620. Januskevicius, Z., Disturbances of cardiac rhythm produced by use of cardiac glycosides, Kardiologiya, 10(2): 35-42, 1970.
2758. Magyarosi, G. H., Therapeutic value of intravenous diphenylhydantoin in digitalis arrhythmia, Rev. Med. Intern., 37(l): 61-6,1985.
2985. Stopfkuchen, H., Gilfrich, H. J., Jungst, B. K., Gempp, W., Massive digoxin intoxication in childhood, Intensive Care Med., 4:199-201, 1978.

Lab. studies:

19. Bigger, J. T., Jr., Bassett, A. L., and Hoffman, B. F., Electrophysiological effects of diphenylhydantoin on canine Purkinje fibers, Circ. Res., 22: 221-236, 1968.
149. Helfant, R. H., Scherlag, B. J., and Damato, A. N., The comparative electrophysiological effects of diphenylhydantoin and procaine amide in the digitalis intoxicated and nondigitalized heart, Clin. Res., 15: 206, 1967.
150. Helfant, R. H., Scherlag, B. J., and Damato, A. N., The use of diphenylhydantoin in ventricular arrhythmias unresponsive to procaine amide: a dissociation of procaine amide’s actions on automaticity and conduction, Circulation, 36: 139, 1967.
151. Helfant, R. H., Scherlag, B. J., and Damato, A. N., Diphenylhydantoin prevention of arrhythmias in the digitalis-sensitized dog after direct-current cardioversion, Circulation, 37: 424-428, 1968.
153. Helfant, R. H., Scherlag, B. J., and Damato, A. N., Electrophysiological effects of direct current countershock before and after ouabain sensitization and after diphenylhydantoin desensitization in the dog, Circ. Res., 22: 615-623, 1968.
154. Helfant, R. H., Scherlag, B. J., and Damato, A. N., The electrophysiological properties of diphenylhydantoin sodium as compared to procaine amide in the normal and digitalis intoxicated heart, Circulation, 36: 108-118, 1967.
155. Helfant, R. H., Scherlag, B. J., and Damato, A. N., Protection from digitalis toxicity with the prophylactic use of diphenylhydantoin sodium: an arrhythmic-inotropic dissociation, Circulation, 36: 119-124, 1967.
233. L.kllmann, H. and Weber, R., On the action of Phenytoin on digitalis-induced arrhythmia, Arztliche Forschung, 22: 49-55, 1968.
249. Mercer, E. N., Ziegler, W. G., Wickland, G. F., and Dower, G. E., The effect of diphenylhydantoin upon beating of heart cells grown in vitro, J. Pharm. Exp. Ther., 155: 267-270, 1967.
260. Mosey, L. and Tyler, M. D., The effect of diphenylhydantoin sodium (Dilantin), procaine hydrochloride, procaine amide hydrochloride, and quinidine hydrochloride upon ouabain-induced ventricular tachycardia in unanesthetized dogs, Circulation, 10: 65-70, 1954.
308. Rosati, R. A., Alexander, J. A., Schaal, S. F., and Wallace, A. G., Influence of diphenylhydantoin on electrophysiological properties of the canine heart, Circ. Res., 21: 757-765, 1967.
327. Scherlag, B. J., Helfant, R. H., and Damato, A. N., The contrasting effects of diphenylhydantoin and procaine amide on A-V conduction in the digitalis-intoxicated and the normal heart, Amer. Heart J., 75: 200-205, 1968.
328. Scherlag, B. J., Helfant, R. H., and Damato, A. N., The relationship between the ionic, inotropic and electrophysiological effects of digitalis, Circulation, 36; 230, 1967.
403. Lüllman, H. and Weber, R., Inhibition of cardiac glycoside-induced arrhythmia by Phenytoin, Naunyn-Schmiedeberg Arch. Pharm., 259: 182-183, 1968.
404. Hilmi, K. I. and Regan, T. J., Relative effectiveness of antiarrhythmic drugs in treatment of digitalis-induced ventricular tachycardia, Amer. Heart J., 76: 365-369, 1968.
405. Mierzwiak, D. S., Mitchell, J. H., and Shapiro, W., The effect of diphenylhydantoin (Dilantin) and quinidine on left ventricular function in dogs, Amer. Heart J., 74: 780-791, 1967.
514. Raines, A., Levitt, B., and Standaert, F. G., Factors influencing diphenylhydantoin antagonism of ouabain-induced ventricular arrhythmia in the cat, Pharmacologist, 9: 237, 1967.
519. Rosati, R. and Wallace, A. G., Electrophysiologic effects of diphenylhydantoin (Dilantin) on the heart of awake dogs, Amer. J. Cardiol., 19: 147, 1967.
685. Helfant, R., Scherlag, B., and Damato, A. N., Protection from digitalis toxicity with prophylactic Dilantin: an electrophysiological-inotropic dissociation, Clin. Res., 15: 206, 1967.
699. Pincus, J. H., Grove, I., Marino, B. B., and Glaser, G. E., Studies on the mechanism of action of diphenylhydantoin, Arch. Neurol., 22: 566-571, 1970.
714. Pincus, J. H., Diphenylhydantoin and sodium influx, Neurology, 20: 393, 1970.
799. Baskin, S. I. and Dutta, S., Effects of antiarrhythrnic drugs and ethacrynic acid on the accumulation of ouabain-H by the isolated guinea pig heart, Fed. Proc., 29: 739, 1970.
800. Baskin, S. I. and Dutta, S., Relationships between prevention of ouabain (O) induced arrhythmia by diphenylhydantoin (DPH) and potassium (K) and their effects on ouabain accumulation and electrolyte composition in the heart, Fed. Proc., 30: 394, 1971.
802. Baskin, S. I., Melrose, B. L., Ferguson, R. K., Akera, T., and Brody, T. M., The effect of diphenylhydantoin on ouabain induced arrhythmia and on the formation and dissociation of the ouabain-enzyrne complex, Personal Communication, 1973.
805. BasuRay, B. N., Dutta, S. N., and Pradhan, S. N., Central action of ouabain: effects of propranolol and diphenylhydantoin on ouabain-induced arrhythmias, Fed. Proc., 30: Abstract 189, 1971.
812. Becker, B. and Podos, S. M., Diphenylhydantoin and its use in optic nerve disease, Symposium an Ocular Therapy, Vol. VI, I. H. Leopold, Ed., C. V. Mosby Co., St. Louis, 1973.
860. Boyd, D. L. and Williams, J. F., The effect of diphenylbydantoin (Dilantin) on the positive inotropic action of ouabain, Amer. J. Cardiol., 23: 712-718, 1969.
963. Diederich, K. W., Herzog, S. and Tielsen, I., Diphenylhydantoin: A comparative study on normal cats and animals intoxicated with digitalis glycosides, Basic Research in Cardiology, 69: 289-308, 1974.
978. Dressier, W. E., Rossi, G. V., and Orzechowski, R. F., Effect of several anticonvulsant drugs and procainamide against ouabain-induced cardiac arrhythmias in rabbits, J. Pharm. Sci., 61: 133-134, 1972.
1079. Godfraind, T., Lesne, M., and Pousti, A., The action of diphenylhydantoin upon drug binding, ionic effects and inotropic action of ouabain, Arch. Int. Pharmacodyn., 191: 66-73, 1971.
1277. Levitt, B., Raines, A., Sohn, Y. J., Standaert, F. G., and Hirshfeld, J. W., The nervous system as a site of action for digitalis and antiarrhythmic drugs, Mt. Sinai Med. J., 37: 227-240, 1970.
1507. Scherlag, B. J., Helfant, R. H., Ricciutti, M. A., Damato, A. N., Dissociation of the effects of digitalis on myocardial potassium flux and contractility, Am. J. Physiology, 215: 1288-1291, 1968.
1663. Watson, E. L. and Woodbury, D. M., The effect of diphenylhydantoin and ouabain, alone and in combination, on the electrocardiogram and on cellular electrolytes of guinea-pig heart and skeletal muscle, Arch. Int. Pharmacodyn.. 201: 389-399, 1973.
1696. Woodbury, D. M. and Kemp, J. W., Pharmacology and mechanisms of action of diphenylhydantoin, Psychial. Neurol. Neurochir., 74: 91-115, 1971.
2224. Loh, C.K., Effects of diphenylhydantoin (DPH) on potassium exchange kinetics and transmembrane potentials in amphibian atrium, Fed. Proc., 33: 445, 1974.
2250. Rhee, H., Antiarrhythmic action of phenytoin (DPH) in dogs: inhibition of Ca + + -ATPase and Ca + + transport, Fed. Proc., 40(3): 645, 1981.
2484. Evans, D. E., Gillis, R. A., Effect of ouabain and its interaction with diphenylhydantoin on cardiac arrhythmias induced by hypothalamic stimulation, J. Pharmacol. Exp. Ther., 195:577-86,1975.
2577. Hashimoto, K., Ishii, M., Komori, S., Mitsuhashi, H., Canine digitalis arrhythmia as a model for detecting Na-channel blocking antiarrhythmic drugs: a comparative study using other canine arrhythmia models and the new antiarrhythmic drugs, propafenone, tocainide, and SUN 1165, Heart Vessels, 1: 29-35,1985.
2676. Kulkarni, S. K., Mehta, A. K., Possible mechanism of digoxin-induced convulsions, Psychopharmacology, 79(2-3) 287-9, 1983.
2723. Lisso, C., Mortari, A., Sioli, C., Marked antiarrhythmic activity of diphenylhydantoin, Atti Accad. Med. Lombarda, 22; 385-90, 1967.
2769. Mathur, K. S., Wahal, P. K., Seth, H. C., Intermittent anomalous atrioventricular excitation (W.P.W. aberation)--an unusual manifestation of digitalis toxicity, Indian Heart J., 21: 249-52, 1969.
2905. Rhee, H. M., Evidence against an involvement of Na+, K+-ATPase in antiarrhythmic mechanism of phenytoin, Naunyn. Schmiedebergs. Arch. Pharmacol., 323(1): 78-84, 1983.
3061. Wasserstrom, J. A., Ferrier, C. R., Effects of phenytoin on digitalis oscillatory after potentials, aftercontractions, and inotropy, Fed. Proc., 39: 1001, 1980.

Gold induced nephropathy: Lab. study: Ref.

1525. Selye, H. and Szabo, S., Protection by various steroids against gold nephropathy, J. Eurap. Toxicol., 6: 512-516, 1972.

Heroin withdrawal: Refs.

290. Ramirez, E., The use of diphenylhydantoin in the modification of acting-out behavior of post-detoxification addict patients, Personal communication. 1967.
1033. Fisher, D. and DiMino, J. M., Case presentation of an alternative therapeutic approach for the borderline psychotic heroin addict: diphenylhydantoin, Br. J. Addict., 70: 51-55, 1975.

Insecticide toxicity: DDT; Refs.

701. Davies, J. E., Edmundson, W. F., Carter, C. H., and Barquet, A., Effect of anticonvulsant drugs on dicophane (D.D.T.) residues in man, Lancet, 2: 7-9, 1969.
943. Davies, J. E., Edmundson, W. F., Maceo, A., Irvin, G. L., Cassady, J., and Barquet, A., Reduction of pesticide residues in human adipose tissue with diphenylhydantoin, Food Cosmet. Toxic., 9: 413-423, 1971.
944. Davies, J. E., Pharmacological depletion of adipose pesticide residues, Clin. Res., 19: 27, 1971.
998. Edmundson, W. F., Davies, J. E., Maceo, A., and Morgade, C., Drug and environmental effects on DDT residues in human blood, Southern Med. J., 63: 1440-1441, 1970.
999. Edmundson, W. F., Frazier, D. E., and Maceo, A., Sequential biochemical tests in persons taking pH phenytoin, Indust. Med., 41: 7-11, 1972.
1253. Kwalick, D. S., Anticonvulsants and DDT residues, JAMA, 215: 120-121, 1971.
1349. McQueen, E. G., Owen, D., and Ferry, D. G., Effect of phenytoin and other drugs in reducing serum DDT levels, New Zeal. Med. J., 75: 208-211, 1972.
1510. Schoor, W. P., Effect of anticonvulsant drugs on insecticide residues, Lancet, 520-521, 1970.
1666. Watson, M., Gabica, J., and Benson, W. W., Serum organochlorine pesticides in mentally retarded patients on differing drug regimens, Clin. Pharmacol. Ther., 13: 186-192, 1972.
2431. Davies, J. E., Edmundson, W. F., The effects of phenytoin on human residues of DDT and dieldrin--a compendium, Epidemiology of DDT. Davies, J. E., Edmundson, W. F., Eds., Futura Publishing Co., 109-23,1979.

Lab. studies: Refs.

823. Bernstein, J. D. and Johnson, S. L., Effects of diphenylhydantoin upon estrogen metabolism by liver microsomes of DDT-treated Japanese quail, Bull. Environ. Confam. Toxicol., 10: 309-314, 1973.
914. Conney, A. H. and Burns, Metabolic interactions among environmental chemicals and drugs, Science, 178: 576-586, 1972.
921. Cranmer, M. F., Effect of diphenylhydantoin on storage of DDT in the rat, Toxic Appl. Pharmacol., 17: 315, 1970.
1022. Ferry, D. G., Owen, D., and McQueen, E. G., The effect of phenytoin on the binding of pesticides to serum proteins, Proc. Univ. Otago Med. School, 50: 8-9, 1972.
3017. Tilson, H. A., Hong, J. S., Mactutus, C. F., Effects of 5,5-diphenylhydantoin (phenytoin) on neurobehavioral toxicity of organochlorine insecticides and permethrin, J. Pharmacol. Exp. Ther., 233(2): 285-9, 1985.

Dieldtin: Ref.

2431. Davies, J. E., Edmundson, W. F., The effects of phenytoin on human residues of DDT and dieldrin-a compendium, Epidemiology of DDT. Davies, J. E., Edmundson, W. F., Eds., Futura Publishing Co., 109-23, 1979.

Organophosphates: Lab. studies: Refs.

2349. Bowles, A. M., Raines, A., Dretchen, K. L., Protection by phenytoin and verapamil against organophosphate poisoning in the mouse, Fed. Proc., 43(3): 553, 1984.
2766. Marx, K. A., Anastasi, N. C., Hernandez, Y. M., Fivozinsky, K. B., Protection by phenytoin against the toxic effects of organophosphate on central respiratory centers, Soc. Neurosci Abstracts, 10: 709, 1984.

Permethrin: Lab. study: Ref.

3017. Tilson, H. A., Hong, J. S., Mactutus, C. F., Effects of 5,5-diphenylhydantoin (phenytoin) on neurobehavioral toxicity of organochlorine insecticides and permethrin, J. Pharmacol. Exp. Ther., 233(2): 285-9, 1985.

Lidocaine induced seizures: Ref.

2916. Rothstein, P., Dornbusch, J., Shaywitz, B. A., Prolonged seizures associated with the use of viscous lidocaine, J. Pediatr., 101: 461-3, 1982.

Lithium induced nervous system toxicity: Ref.

1637. Van Der Velde, C. D., Toxicity of lithium carbonate in elderly patients, Amer. J. Psychiat., 127: 1075-1077, 1971.

LSD (lysergic acid diethylamide) toxicity: Refs.

1616. Thurlow, H. J. and Girvin, J. P., Use of anti-epileptic medication in treating “flashbacks” from hallucinogenic drugs, Canad. Med. Assoc. J., 105: 947-948, 1971.

1904. Ifabumuyi, O. I. and Jeffries, J. J., Treatment of drug-induced psychosis with diphenylhydantoin, Can. Psychiatr. Assoc. J., 21: 565-9, 1976.

Mephenytoin: Lab. study: Ref.

567. Weaver, L. C., Swinyard, E. A., and Goodman, L. S., Anticonvulsant drug combinations: diphenylhydantoin combined with other antiepileptics, J. Amer. Pharm. Assn., 47: 645-648, 1958.

Mephobarbital: Lab. study: Ref.

567. Weaver, L. C., Swinyard, E. A., and Goodman, L. S., Anticonvulsant drug combinations: diphenylhydantoin combined with other antiepileptics, J. Amer. Pharm. Assn., 47: 645-648, 1958.

Methaqualone intoxication: Lab. study: Ref

1529. Selye, H., Szabo, S., and Kourounakis, P., Protection by catatoxic steroids, phenobarbital and diphenylhydantoin against methaqualone intoxication, Steroids Lipids Res., 3: 156-159, 1972.

Metrizamide induced neurotoxicity and seizures in patients undergoing neuroradiological procedures: Refs.

2709. Levin, R., Lee, S. I., Nonconvulsive status epilepticus following metrizamide myelogram, Ann. Neurol., 17(5): 518-19, 1985.
2882. Pritchard, P. B., O’Neal, D. B., Nonconvulsive status epilepticus following metrizamide myelography, Ann. Neurol., 16: 252-4, 1984.
3054. Wagner, J. H., Another report of nonconvulsive status epilepticus after metrizamide myelography, Ann. Neurol., 18(3): 369-70, 1985.

Misonidazole induced peripheral neuropathy: Refs.

2114. Wasserman, T. H., Phillips, T. L., Van Raalte, G., Urtasun, R., Partington, J., Koziol, D., Schwade, J. G., Gangji, D. and Strong, J. M., The neurotoxicity of misonidazole: potential modifying role by phenytoin sodium and dexamethasone, Br. J. Radiol., 53: 172-3, 1980.
2342. Bleehen, N. M., The Cambridge glioma trial of misonidazole and radiation therapy with associated pharmacokinetic studies, Cancer Clin., 3: 267-73, 1980.
2868. Phillips, T. L., Wasserman, T. H., Johnson, R. J., Levin, V. A., Vanraalte, G., Final report on the United States phase 1 clinical trial of the hypoxic cell radiosensitizer, misonidazole (Ro-07-0582; NSC 261037), Cancer, 48: 1697-1704, 1981.
3060. Wasserman, T. H., Stetz, J., Phillips, T. L., Radiation therapy oncology group clinical trials with misonidazole, Cancer, 47: 2382-90, 1981.

Morphine withdrawal and mania: Lab. studies: Refs.

1026. Fertziger, A. P., Lynch, J. J., and Stein, E. A., Modification of the morphine withdrawal syndrome in rats, Brain Res., 78:331-334, 1974.
1027. Fertziger, A. P., Stein, E. A., and Lynch, J. J., Suppression of morphine-induced mania in cats, Psychopharmacologia, 36: 185-187, 1974.
1781. Cookson, S. L. and Mann, J. D., Reversal and prevention of acute morphine induced catalepsy by phenytoin in naive rats, Neurosci. Abstr., 4: 488, 1978.
2062. Saad, S. F., Osman, 0. H., Mustafa, A. and Hussein, K. E., Possible involvement of gamma-aminobutyric acid in morphine abstinence in rats, IRCS Med. Sci., 5(7): 317, 1977.

Phenothiazine induced neuroteptic malignant syndrome: Ref.

2822. Neppe, V. M., The neuroleptic malignant syndrome, S. Afr. Med. J., 65: 523-5, 1984.

Polychlorinated biphenyl (PCB) toxicity (carcinogenesis): Ref.

2583. Hayashi, K., Takemura, N., Inhibition of PCB accumulation in liver and fat of rats by administration of diphenylhydantoin, Jpn. J. Ind. Health, 17: 242-3, 1975.

Reserpine induced hyperexcitability, rigidity and hypothermia: Lab. studies: Refs.

82. Dreifus, L. S., Rabbino, M. D., and Watanabe, V., Newer agents in the treatment of cardiac arrythmias, Med. Clin. N. Amer., 48: 371-387, 1964.
183. Jurna, 1. and Regélhy, B., The antagonism between reserpine and some antiparkinson drugs in electroseizure, Naunyn-Schmiedeberg Arch. Pharm., 259: 442-459, 1968.
1306. Lotti, V. J., Torchiana, M. L., and Porter, C. C., Investigations on the action and mechanism of action of diphenylhydantoin as an antagonist of tetrabenazine and reserpine, Arch. Int. Pharmacodyn., 203: 107-116, 1973.
1643. Van Riezen, H. and Delver, A., The effect of a number of drugs with different pharmacological properties upon reserpine induced hypothermia in mice, Arzneimittelforschung., 21: 1562-1566, 1971.

Spider and snake venom: Refs.

1844. Gage, P. W. and Spence, I., The origin of the muscle fasciculation caused by funnel-web spider venom, Epilepsy Abstracts, 11(9): 364, 1978.
2789. Mercer, H. P., McGill, J. J., Ibrahim, R. A., Envenomation by sea snake in Queensland, Med. J. Aust., 1: 130-2, 1981.

Steroid induced muscle weakness and skin changes: Refs.

377. Werk, E. E., Jr., MacGee, J., and Sholiton, L. J., Effect of diphenylhydantoin on cortisol metabolism in man, J. Clin. Invest., 43: 1824-1835, 1964.
425. Werk, E. E., Sholiton, L. J., and Olinger, C. P., Enzyme inducer, New Eng. J. Med., 276: 877, 1967.
896. Choi, Y., Thrasher, K., Werk, E. E., Sholiton, L. J., and Olinger, C., Effect of diphenylhydantoin on cortisol kinetics in humans, J. Pharmacol. Exp. Ther., 176: 27-34, 1971.
1128. Hague, N., Thrasher, K., Werk, E. E., Jr., Knowles, H. C., J r., and Sholiton, L. J., Studies on dexamethasone metabolism in man: effect of diphenylhydantoin, J. Clin. Endocr., 34: 44-50, 1972.
1594. Stern, L. Z., Gruener, R., and Amundsen, P., Diphenylhydantoin for steroid-induced muscle weakness, JAMA, 223: 1287-1288, 1973.

Lab. studies: Refs.

171. Houck, J. C. and Patel, Y. M., Proposed mode of action of corticosteroids on the connective tissue, Nature, 206: 158-160, 1965.
451. Sholiton, L., Werk, E.E., Jr. and MacGee, J., The in vitro effect of 5,5 2-diphenylhydantoin on the catabolism of cortisol by rat liver, Metabolism, 13: 1382-1392, 1964.
482. Oliver, J. T. and Troop, R. C., Plasma corticosterone levels in stressed rats following the administration of pentobarbital, morphine and diphenylhydantoin, Steroids, 1: 670-677, 1963.
483. Woodbury, D. M., Timiras, P. S., and Vernadakis, A., Modification of adrenocartical function by centrally acting drugs and the influence of such modification on the central response to these drugs, Hormones, Brain Function, and Behavior, 38-50, H. Hoagland, Ed., Academic Press, New York, 1957.
504. Kolbert, G. S., Oral diphenylhydantoin in corneal wound healing in the rabbit, Amer. J. Ophthal., 66: 736-738, 1968.
1103. Gruener, R. P. and Stern, L. Z., Diphenylhydantoin reverses membrane effects in steroid myopathy, Nature New Bio., 235: 54-55, 1972.
2063. Sabai, Y., Kobayashi, K. and Iwata, M., Effects of an anabolic steroid and vitamin B complex upon myopathy induced by corticosteroids, European J. Pharmacol., 52: 353-9, 1978.

Streptozotocin induced diabetes: Lab. study: Ref

1509. Schimmel, R. J., and Graham, D., Inhibition by diphenylhydantoin of the diabetogenic action of streptozotocin, Horm. Metab. Res., 6: 475-477, 1974.

Strychnine toxicity: Ref.

625. Cotten, M. S. and Lane, D. H., Massive strychnine poisoning: a successful treatment, J. Mississippi Med. Assn., 7: 466-468, 1966.

Lab. studies: Refs.

90. Esplin, D. W., Effects of diphenylhydantoin on synaptic transmission in cat spinal cord and stellate ganglion, J. Pharm. Exp. Ther., 120: 301-323, 1957.
1208. Kato, R., Chiesara, E., and Vassanelli, P., Increased activity of microsomal strychnine-rnetabolizing enzyme induced by phenobarbital and other drugs, Biochem. Pharmacol., 11: 913-922, 1962.
2662. King, R. B., Barnett, J. C., Studies of trigeminal nerve potentials, J. Neurosurg., 14: 617-27, 1957.
2724. Lloyd, K. G., Worms, P., GABA agonists: their potential as anticonvulsant drugs, Br. Assoc. Psychopharmacol, Monogr., 2: 54-61, 1982.
2774. Matthews, W. D., McCafferty, C. P., Anticonvulsant activity of muscimol against seizures induced by impairment of GABA-mediated neurotransmission, Neuropharmacology, IS: 885-9, 1979.

Succinylcholine induced muscle fasciculation: Lab. studies: Refs.

1494. Rutledge, R., Sohn, Y. J., and Sardinas, A., Interaction of diphenylhydantoin and succinylcholine at the neuromuscular junction, Pharmacologist, 13: 265, 1971.
2576. Hartman, G. S., Flamengo, S. A., Riker, W. F., Suceinylcholine: mechanism of fasciculations and their prevention by d-tubocurarine or diphenylhydantoin, Anesthesiology, 65(4): 405-13, 1986.

Tetanus toxin: Refs.

2359. Brown, H., Tetanus, JAMA, 204(7) 614-16, 1968.
2913. Rodriguez-Noriega, E., Perez-Ruvalcaba, J. A., Quintero-Perez, N. P., Hernandez-Bugarin, O., Macias-Hernandez, O., Chapa-Alvarez, J. R., Andrade-Perez, J. S., The effect of phenytoin on muscle spasms and the hyperactive sympathetic syndrome of tetanus, Eur. J. Clin. Invest., 14; 36, 1984.

Trimethadione: Lab. study: Ref.

567. Weaver, L. C., Swinyard, E. A., and Goodman, L. S., Anticonvulsant drug combinations: diphenylhydantoin combined with other antiepileptics, J. Amer. Pharm. Assn., 47: 645-648,1958.


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