Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1971 Nov;43(3):483–496. doi: 10.1111/j.1476-5381.1971.tb07179.x

Inotropic actions of lignocaine and phenytoin

Barbara L Kennedy, Chongkol Nookhwun, Chiravat Sadavongvivad, S Tanchajja
PMCID: PMC1665795  PMID: 4110251

Abstract

1. The inotropic effects of two antiarrhythmic drugs, lignocaine and phenytoin, were studied in electrically driven isolated rabbit atrial preparations. The time-effect relationship of each drug was investigated with different concentrations and frequencies of stimulation.

2. The effects of time of exposure, drug concentration and heart rate on the development of beat alterations (cessation of beat, skipped beat, alternating variation of force of contraction and extrasystole) were also studied.

3. When the chronotropic effects of both drugs were prevented, the inotropic effects were positive or negative depending on the concentration of drug, time of exposure and frequency of stimulation.

4. At concentrations higher than those obtained in the blood of man on maintenance doses, alteration of the beat occurred but was consistent with the peak blood concentrations immediately after the injection of standard clinical doses. The time of onset of beat alteration shortened when either drug concentration or frequency of stimulation was increased.

5. The beat alteration produced by antiarrhythmic drugs can account for various adverse effects associated with their clinical use. These effects include transient ventricular tachycardia and extrasystole during and shortly after injection of drug, ventricular tachycardia, ventricular fibrillation and cardiac arrest due either to excessive dose or to persistent tachyarrhythmia if the dose is not excessive.

Full text

PDF
483

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Austen W. G., Moran J. M. Cardiac and peripheral vascular effects of lidocaine and procainamide. Am J Cardiol. 1965 Nov;16(5):701–707. doi: 10.1016/0002-9149(65)90054-8. [DOI] [PubMed] [Google Scholar]
  2. Bigger J. T., Jr, Bassett A. L., Hoffman B. F. Electrophysiological effects of diphenylhydantoin on canine purkinje fibers. Circ Res. 1968 Feb;22(2):221–236. doi: 10.1161/01.res.22.2.221. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. CONN H. L., Jr, LUCHI R. J. Ionic influences on quinidinealbumin interaction. J Pharmacol Exp Ther. 1961 Jul;133:76–83. [PubMed] [Google Scholar]
  5. Chopra M. P., Portal R. W., Aber C. P. Lignocaine therapy after acute myocardial infarction. Br Med J. 1969 Jan 25;1(5638):213–216. doi: 10.1136/bmj.1.5638.213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Covino B. G., Shannon C. M. Effect of several new antiarrhythmic agents on atrial contractility. Arch Int Pharmacodyn Ther. 1969 Mar;178(1):185–192. [PubMed] [Google Scholar]
  7. Gellerman G. L., Martinez C. Fatal ventricular fibrillation following intravenous sodium diphenylhydantoin therapy. JAMA. 1967 Apr 24;200(4):337–338. [PubMed] [Google Scholar]
  8. Goldschlager A. W., Karliner J. S. Ventricular standstill after intravenous diphenylhydantoin. Am Heart J. 1967 Sep;74(3):410–412. doi: 10.1016/0002-8703(67)90082-8. [DOI] [PubMed] [Google Scholar]
  9. KOCH-WESER J., BLINKS J. R. THE INFLUENCE OF THE INTERVAL BETWEEN BEATS ON MYOCARDIAL CONTRACTILITY. Pharmacol Rev. 1963 Sep;15:601–652. [PubMed] [Google Scholar]
  10. Kaufmann G. Lignocaine for arrhythmias. Lancet. 1968 Apr 20;1(7547):862–862. doi: 10.1016/s0140-6736(68)90327-9. [DOI] [PubMed] [Google Scholar]
  11. Kennedy B. L., West T. C. Factors influencing quinidine-induced changes in excitability and contractility. J Pharmacol Exp Ther. 1969 Jul;168(1):47–59. [PubMed] [Google Scholar]
  12. LYON A. F., DEGRAFF A. C. ANTIARRHYTHMIC DRUGS. II. CLINICAL USE OF QUINIDINE. Am Heart J. 1965 Jun;69:834–837. doi: 10.1016/0002-8703(65)90458-8. [DOI] [PubMed] [Google Scholar]
  13. Lown B., Vassaux C. Lidocaine in acute myocardial infarction. Am Heart J. 1968 Oct;76(4):586–587. doi: 10.1016/0002-8703(68)90148-8. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Mierzwiak D. S., Mitchell J. H., Shapiro W. The effect of diphenylhydantoin (Dilantin) and quinidine on left ventricular function in dogs. Am Heart J. 1967 Dec;74(6):780–791. doi: 10.1016/0002-8703(67)90097-x. [DOI] [PubMed] [Google Scholar]
  16. Nagle R. E., Pilcher J. Lignocaine for arrythmias. Lancet. 1968 May 11;1(7550):1039–1039. doi: 10.1016/s0140-6736(68)91152-5. [DOI] [PubMed] [Google Scholar]
  17. Nayler W. G., McInnes I., Swann J. B., Race D., Carson V., Lowe T. E. Some effects of diphenylhydantoin and propranolol on the cardiovascular system. Am Heart J. 1968 Jan;75(1):83–96. doi: 10.1016/0002-8703(68)90119-1. [DOI] [PubMed] [Google Scholar]
  18. Pruett J. K., Woods E. F. The relationship of intracellular depolarization rates and contractility in the dog ventricle in situ: effects of positive and negative inotropic agents. J Pharmacol Exp Ther. 1967 Jul;157(1):1–7. [PubMed] [Google Scholar]
  19. SELZER A., WRAY H. W. QUINIDINE SYNCOPE. PAROXYSMAL VENTRICULAR FIBRILLATION OCCURRING DURING TREATMENT OF CHRONIC ATRIAL ARRHYTHMIAS. Circulation. 1964 Jul;30:17–26. doi: 10.1161/01.cir.30.1.17. [DOI] [PubMed] [Google Scholar]
  20. Stannard M., Sloman G., Sangster L. Haemodynamic effects of lignocaine in acute myocardial infarction. Br Med J. 1968 May 25;2(5603):468–469. doi: 10.1136/bmj.2.5603.468. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Unger A. H., Sklaroff H. J. Fatalities following intravenous use of sodium diphenylhydantoin for cardiac arrhythmias. Report of two cases. JAMA. 1967 Apr 24;200(4):335–336. [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES