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. 1975 Jul;37(7):731–740. doi: 10.1136/hrt.37.7.731

Procainamide and phenytoin. Comparative study of their antiarrhythmic effects at apparent therapeutic plasma levels.

E Karlsson
PMCID: PMC482865  PMID: 1098684

Abstract

The antiarrhythmic effects of procainamide and phenytoin were studied in 81 patients admitted to the coronary care unit at the University Hospital in Linköping because of a suspected or proven diagnosis of acute myocardial infarction, and who developed ventricular arrhyhmias, requiring treatment, during the first 8 hours in hospital. Patients were randomly allocated to a procainamide of phenytoin group. The drugs were given as intravenous and oral loading doses followed by oral maintenance therapy. Plasma levels of the two druge were frequently determined and the electrocardiogram was continuously recorded during the 24-hour trial and analysed minute by minute. A significantly higher frequency of therapeutic failure was found in the phenytoin group (23 of 35 patients)compared to the procainamide group(13 of 39 aptients) during the first 2 hours after initiation of therapy. Four patients in the phenytoin group and 2 in the procainamide group developed symptoms probably caused by the trial drugs, necessitating discontinuation of therapy. The mean plasma levels were usually within the apparent therapeutic range (for phenytoin 40-72 mumol/l (10-18 mug/ml), and for procainamide 17-34 mumol/l (4-8 mug/ml). Seventeen patients (68%) in the phenytoin group and 10 patients (48%) in the procainamide group had plasma concentrations within this range when the therapeutic failure was observed. Nine patients died in hospital but only one of them during the trial. The results of this investigation clearly demonstrate the overall superiority of procainamide over phenytoin as an antiarrhythmic drug in short-term therapy after acute myocardial infarction.

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Selected References

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  1. Arnold K., Gerber N. The rate of decline of diphenylhydantoin in human plasma. Clin Pharmacol Ther. 1970 Jan-Feb;11(1):121–134. doi: 10.1002/cpt1970111121. [DOI] [PubMed] [Google Scholar]
  2. Arstila M., Katila M., Sundquist H., Anttila M., Pere E., Tikkanen R. Dosage, plasms concentration and antiarrhythmic effect of procainamide in sustained-release tablets. Acta Med Scand. 1974 Mar;195(3):217–222. doi: 10.1111/j.0954-6820.1974.tb08125.x. [DOI] [PubMed] [Google Scholar]
  3. Bennett M. A., Pentecost B. L. Warning of cardiac arrest due to ventricular fibrillation and tachycardia. Lancet. 1972 Jun 24;1(7765):1351–1352. doi: 10.1016/s0140-6736(72)91090-2. [DOI] [PubMed] [Google Scholar]
  4. Berlin A., Agurell S., Borgå O., Lund L., Sjöqvist F. Micromethod for the determination of diphenylhydantoin in plasma and cerebrospinal fluid--a comparison between a gas chromatographic and a spectrophotometric method. Scand J Clin Lab Invest. 1972 May;29(3):281–287. doi: 10.3109/00365517209080243. [DOI] [PubMed] [Google Scholar]
  5. Bigger J. T., Jr, Schmidt D. H., Kutt H. Relationship between the plasma level of diphenylhydantoin sodium and its cardiac antiarrhythmic effects. Circulation. 1968 Aug;38(2):363–374. doi: 10.1161/01.cir.38.2.363. [DOI] [PubMed] [Google Scholar]
  6. Bissett J. K., De Soyza N. D., Kane J. J., Murphy M. L. Improved intraventricular conduction of premature beats after diphenylhydantoin. Am J Cardiol. 1974 Apr;33(4):493–497. doi: 10.1016/0002-9149(74)90607-9. [DOI] [PubMed] [Google Scholar]
  7. Damato A. N., Berkowitz W. D., Patton R. D., Lau S. H. The effect of diphenylhydantoin on atrioventricular and intraventricular conduction in man. Am Heart J. 1970 Jan;79(1):51–56. doi: 10.1016/0002-8703(70)90393-5. [DOI] [PubMed] [Google Scholar]
  8. Dhurandhar R. W., MacMillan R. L., Brown K. W. Primary ventricular fibrillation complicating acute myocardial infarction. Am J Cardiol. 1971 Apr;27(4):347–351. doi: 10.1016/0002-9149(71)90429-2. [DOI] [PubMed] [Google Scholar]
  9. Gamble O. W., Cohn K. Effect of propranolol, procainamide, and lidocaine on ventricular automaticity and reentry in experimental myocardial infarction. Circulation. 1972 Sep;46(3):498–506. doi: 10.1161/01.cir.46.3.498. [DOI] [PubMed] [Google Scholar]
  10. Giardina E. G., Heissenbuttel R. H., Bigger J. T., Jr Intermittent intravenous procaine amide to treat ventricular arrhythmias. Correlation of plasma concentration with effect on arrhythmia, electrocardiogram, and blood pressure. Ann Intern Med. 1973 Feb;78(2):183–193. doi: 10.7326/0003-4819-78-2-183. [DOI] [PubMed] [Google Scholar]
  11. Glazko A. J., Chang T., Baukema J., Dill W. A., Goulet J. R., Buchanan R. A. Metabolic disposition of diphenylhydantoin in normal human subjects following intravenous administration. Clin Pharmacol Ther. 1969 Jul-Aug;10(4):498–504. doi: 10.1002/cpt1969104498. [DOI] [PubMed] [Google Scholar]
  12. Helfant R. H., Scherlag B. J., Damato A. N. Diphenylhydantoin prevention of arrhythmias in the digitalis-sensitized dog after direct-current cardioversion. Circulation. 1968 Mar;37(3):424–428. doi: 10.1161/01.cir.37.3.424. [DOI] [PubMed] [Google Scholar]
  13. Helfant R. H., Scherlag B. J., Damato A. N. Protection from digitalis toxicity with the prophylactic use of diphenylhydantoin sodium. An arrhythmic-inotropic dissociation. Circulation. 1967 Jul;36(1):119–124. doi: 10.1161/01.cir.36.1.119. [DOI] [PubMed] [Google Scholar]
  14. Helfant R. H., Seuffert G. W., Patton R. D., Stein E., Damato A. N. The clinical use of diphenylhydantoin (dilantin) in the treatment and prevention of cardiac arrhythmias. Am Heart J. 1969 Mar;77(3):315–323. doi: 10.1016/0002-8703(69)90187-2. [DOI] [PubMed] [Google Scholar]
  15. JULIAN D. G., VALENTINE P. A., MILLER G. G. DISTURBANCES OF RATE, RHYTHM AND CONDUCTION IN ACUTE MYOCARDIAL INFARCTION: A PROSPECTIVE STUDY OF 100 CONSECUTIVE UNSELECTED PATIENTS WITH THE AID OF ELECTROCARDIOGRAPHIC MONITORING. Am J Med. 1964 Dec;37:915–927. doi: 10.1016/0002-9343(64)90133-0. [DOI] [PubMed] [Google Scholar]
  16. Josephson M. E., Caracta A. R., Ricciutti M. A., Lau S. H., Damato A. N. Electrophysiologic properties of procainamide in man. Am J Cardiol. 1974 May 6;33(5):596–603. doi: 10.1016/0002-9149(74)90248-3. [DOI] [PubMed] [Google Scholar]
  17. Karlsson E. Plasma levels of procaine amide after administration of conventional and sustained-release tablets. Eur J Clin Pharmacol. 1973 Dec;6(4):245–250. doi: 10.1007/BF00644740. [DOI] [PubMed] [Google Scholar]
  18. Koch-Weser J., Klein S. W. Procainamide dosage schedules, plasma concentrations, and clinical effects. JAMA. 1971 Mar 1;215(9):1454–1460. [PubMed] [Google Scholar]
  19. Lown B., Wolf M. Approaches to sudden death from coronary heart disease. Circulation. 1971 Jul;44(1):130–142. doi: 10.1161/01.cir.44.1.130. [DOI] [PubMed] [Google Scholar]
  20. Lunde P. K., Rane A., Yaffe S. J., Lund L., Sjöqvist F. Plasma protein binding of diphenylhydantoin in man. Interaction with other drugs and the effect of temperature and plasma dilution. Clin Pharmacol Ther. 1970 Nov-Dec;11(6):846–855. doi: 10.1002/cpt1970116846. [DOI] [PubMed] [Google Scholar]
  21. Mercer E. N., Osborne J. A. The current status of diphenylhydantoin in heart disease. Ann Intern Med. 1967 Nov;67(5):1084–1107. doi: 10.7326/0003-4819-67-5-1084. [DOI] [PubMed] [Google Scholar]
  22. Rosen M., Lisak R., Rubin I. L. Diphenylhydantoin in cardiac arrhythmias. Am J Cardiol. 1967 Nov;20(5):674–678. doi: 10.1016/0002-9149(67)90011-2. [DOI] [PubMed] [Google Scholar]
  23. SVENSMARK O., SCHILLER P. J., BUCHTHAL F. 5, 5-Diphenylhydantoin (dilantin) blood levels after oral or intravenous dosage in man. Acta Pharmacol Toxicol (Copenh) 1960;16:331–346. doi: 10.1111/j.1600-0773.1960.tb01218.x. [DOI] [PubMed] [Google Scholar]
  24. Scheinman M. M., Weiss A. N., Shafton E., Benowitz N., Rowland M. Electrophysiologic effects of procaine amide in patients with intraventricular conduction delay. Circulation. 1974 Mar;49(3):522–529. doi: 10.1161/01.cir.49.3.522. [DOI] [PubMed] [Google Scholar]
  25. Schwartz M. L., Webb N. C., Covino B. G., Finck E. M., Haider B. Comparative antiarrhythmic effects of intravenously administered lidocaine and procainamide and orally administered quinidine. Am J Cardiol. 1970 Nov;26(5):520–523. doi: 10.1016/0002-9149(70)90710-1. [DOI] [PubMed] [Google Scholar]
  26. Stone N., Klein M. D., Lown B. Diphenylhydantoin in the prevention of recurring ventricular tachycardia. Circulation. 1971 Mar;43(3):420–427. doi: 10.1161/01.cir.43.3.420. [DOI] [PubMed] [Google Scholar]
  27. Weisse A. B., Moschos C. B., Passannante A. J., Khan M. I., Regan T. J. Relative effectiveness of three antiarrhythmic agents in the treatment of ventricular arrhythmias in experimental acute myocardial ischemia. Am Heart J. 1971 Apr;81(4):503–510. doi: 10.1016/0002-8703(71)90366-8. [DOI] [PubMed] [Google Scholar]

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