Summary
The effects of drug combinations have certain characteristic properties produced by the interaction of the physiological-pharmacological effects of the constituents. The results may be:
-
1.
Inapparent. Potential interaction between drugs may be of little significance or even quite inapparent, if the side-effects are opposite in nature and equal in strength.
-
2.
Antagonistic. Some types of antagonism may be dangerous, or they may be merely inconvenient.
-
3.
Synergistic. Synergistic action of drugs may result from(a) summated actions, and/or(b) potentiated actions which may be desirable if unwanted side-effects of each component can be “filtered out,” butundesirable if unforeseen exaggeration of the desired effect occurs.
With greater awareness and understanding of the underlying mechanisms, the many untoward interactions now being increasingly reported might be foreseen and avoided.
Résumé
Le médecin, le pharmacien et le représentant des manufacturiers de produits pharmaceutiques ont une responsabilité envers le public dans la présentation des médicaments.
Récemment, on a attiré l’attention sur les problèmes et les risques reliés à l’interaction des médicaments entr’eux. Au cours des dernières années, la possibilité d’interaction entre les médicaments a augmenté de façon marquée. Dans la pratique de l’anesthésie, la chose est plus patente.
Les situations cliniques, en anesthésie, où l’interaction entre les médicaments peut s’observer sont: (1) Lors d’un simple mélange. (2) Lors de l’administration par le même anesthésiste de doses séparées de différents médicaments à de courts intervalles. (3) Lors de l’administration de médicaments par différents médecins (chirurgiens, médecins traitants et anesthésistes) qui ignorent que d’autres médicaments ont été donnés.
Les endroits et les mécanismes de l’interaction des médicaments sont: (1) l’interaction directe, (2) l’interaction au site d’absorption, (3) l’interaction de transport (déplacement de l’association avec les protéines du plasma), (4) à l’endroit des récepteurs, (5) en accélérant ou en ralentissant le métabolisme des médicaments, (6) en agissant sur l’excrétion.
Les effets de l’interaction des médicaments entre eux résultent de leur combinaison qui modifie leurs propriétés caractéristiques par l’interaction des effets pharmaceutiques et physiologiques des constituents. Il peut s’ensuivre: (1) aucun symptome (si les effets sont égaux et opposés), (2) un antagonisme, (3) une synergie (pouvant inclure une sommation et une potentialisation.
Nous avons cité des exemples de médicaments associés à l’anesthésie et à la chirurgie qui ont présenté des phénomènes d’interaction et nous avons parlé de l’influence de ces interactions sur la conduite de l’anesthésie.
En étant plus averti et en comprenant mieux les mécanismes en cause, il est possible de prévoir et d’éviter les nombreuses interactions indésirables que l’on observe et que l’on rapporte de plus en plus.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Macgregor, A. G. Symposium on Interaction between Drugs, Proc. Roy. Soc. Med. 58:943 (1965).
Editorial: Interaction of Drugs. Brit.M.J. J: 811-812 (1966).
Jick, H. &Chalmers, T. C. Editorial: Drug Combinations—Uses, Dangers and Fallacies. Clin. Pharmacol. & Therap. 5: 673 (1964).
Wilson, G. M. The Interaction of Drugs in Medicine. In Symposium on Clinical Trials. Pharmaceutical Society of Great Britain. London (1962), p. 53.
Cluff, L. E. Studies on the Epidermiology of Adverse Drug Reactions: I. Methods of Surveillance. J.A.M.A.,188: 976 (1964).
Jenkins, L. C. &Graves, H. B. Potential Hazards of Psychoactive Drugs in Association with Anaesthesia. Canad. Anaesth. Soc. J.,12: 121 (1965).
Chargaff, E. &Olson, K. B. Studies on the Chemistry of Blood Coagulation: VI. Studies on the Action of Heparin and Other Anticoagulants: The Influence of Protamine on the Anticoagulant Effectin Vivo. J. Biol. Chem.,122: 153 (1937).
Brodde, B. B. Displacement of One Drug by Another from Carrier or Receptor Sites: In Symposium on Interaction between Drugs. Proc. Roy. Soc. Med.58: 946 (1965).
Christensen, L. K.;Hansen, J. M.; &Kristensen, M. Sulphaphenazole-induced Hypo-glycaemia Attacks in Tolbutamide-treated Diabetes. Lancetii: 1298 (1963).
Eisen, M. J. Combined Effect of Sodium Warfarin and Phenylbutazone, J.A.M.A.189: 64 (1964).
Usubiaga, J. E.;Wikinski, J. A.;Morales, R. L.; &Usubiaga, L. E. J. Interaction of Intravenously Administered Procaine, Lidocaine and Succinylcholine in Anesthetized Subjects. Anesth. & Analg.46: 39 (1967).
De Kornfeld, T. J. &Steinhaus, J. E. The Effect of Intravenously Administered Lidocaine and Succinylcholine on the Respiratory Activity of Dogs. Anesth. & Analg. 38: 173(1959).
Parada, I. F. &Malina, F. J. Intravenous Procaine Anesthesia: An Argentine Technique. Proc. First European Cong. Anesth.2: 152 (1962).
Usubiaga, J. E. &Wikinski, J. A. Uso da procaina intravenosa em anestesia general. Rev. brasil. Anest.14: 400 (1964).
Goodman, L. S. &Gilman, A. The Pharmacological Basis of Therapeutics. New York: Macmillan (1965), 523, 569, 500, 846.
Lown, B. &Levine, H. D. Atrial Arrhythmias, Digitalis and Potassium. New York: Landsberger Medical Books (1958).
Asatoor, A. M.;Galman, B. R.;Johnson, J. R.; &Milne, M. D. The Excretion of Dexamphetamine and Its Derivatives. Brit. J. Pharmacol.24: 293 (1965).
Milne, M. D. Influence of Acid-Base Balance on Efficiency and Toxicity of Drugs. In Symposium on Interaction between Drugs. Proc. Roy. Soc, Med.58: 961 (1965).
Burns, J. J. &Conney, A. H. Enzyme Stimulation and Inhibition with Metabolism of Drugs. In Symposium on Interaction between Drugs. Proc. Roy. Soc. Med.58: 955 (1965).
Conney, A. H. &Burns, J. J. Factors Influencing Drug Metabolism. Adv. Pharmacol.1: 31 (1962).
Remmer, H. Enzyme Induction and Inhibition. In Ciba Foundation Symposium on Enzymes and Drug Action. Ed. J. L. Mongar and A. V. S. De Reuck. Boston (1962), p. 276.
Burns, J. J. Editorial: Implications of Enzyme Induction for Drug Therapy. Am. J. Med.37: 327 (1964).
Fouts, J. R. Editorial: Drug Interactions: Effects of Drugs and Chemicals on Drug Metabolism. Gastroenterology.46: 486 (1964).
Burns, J. J.;Rose, R. K.;Goodwin, S.;Reichenthal, J.;Horning, E. C; &Brodie, B. B. The Metabolic Fate of Phenylbutazone (Butazolidin) in Man. J. Pharmacol. Exper. Therap.113: 481 (1955).
Burns, J. J.;Conney, A. H.;Colville, K. I.; &Sansur, M. Interaction between Drugs. Pharmacologist. 5: 250 (1963).
Weiner, M.;Siddiqui, A. A.;Bostanci, N.; &Dayton, P. G., Drug Interactions: The Effect of Combined Administration on the Half-life of Coumarin and Pyrazolone Drugs in Man. Fed. Proc.24: 153 (1965).
Conney, A. H. & Burns, J. J. Enzyme Induction. In Symposium on Regulation of Enzyme Activity and Synthesis in Normal and Neoplastic Liver. Ed. G. Weliu. New York (1963), p. 189.
Fouts, J. R. &Rogers, L. A. Morphological Changes in the Liver Accompanying Stimulation of Microsomal Drug Metabolizing Enzyme Activity by Phénobarbital, Chlordane, Benzpyrene or Methylcholanthrene in Rats. J. Pharmacol. Exper. Therap.147: 112 (1965).
Conney, A. H.;Davison, C;Gostel, R.; &Burns, J. J. Adaptive Increases in Drug-metabolizing Enzymes Induced by Phenobarbital and Other Drugs, J. Pharmacol. Exper. Therap.130: 1 (1960).
Cucinell, S. A.;Odessky, L.;Weiss, M.; &Dayton, P. G. The Effect of Chloral Hydrate on Bishydroxycoumarin Metabolism: A Fatal Outcome. J.A.M.A.197: 366 (1966).
Cucinell, S. A.;Conney, A. H.;Sansur, M.; &Burns, J. J. Drug Interactions in Man. I. Lowering Effect of Phenobarbital on Plasma Levels of Bishydroxycoumarin (Dicumarol) and Diphenylhydrantoin (Dilantin). Clin. Pharmacol. Therap.6: 420 (1965).
Cucinell, S. A.;Koster, R.;Conney, A. H. &Burns, J. J. Stimulatory Effect of Phenobarbital on the Metabolism of Diphenylhydantoin. J. Pharmacol. & Exper. Therap.141: 157(1963).
Busfield, D.;Child, K. J.; &Tomich, E. G. An Effect of Phenobarbitone on Griseofulvin Metabolism in the Rat. Brit. J. Pharmacol.22: 137 (1964).
Burns, J. J.;Cucinell, S. A.;Koster, R.; &Conney, A. H. Application of Drug Metabolism to Drug Toxicity Studies. Ann. N.Y. Acad. Sc.123: 273 (1965).
Werk, E. E. Jr.;MacGee, J.; &Sholiton, L. J. Effect of Diphenylhydantoin on Cortisal Metabolism in Man. J. Clin. Invest.43: 1824 (1964).
Shepherd, M. Psychotropic Drugs: I. Interaction between Centrally Acting Drugs in Man: Some General Considerations. In Symposium on Interaction between Drugs. Proc. Roy. Soc. Med.58: 964 (1965).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Jenkins, L.C. The interaction of drugs, with particular reference to anaesthetic practice. Can. Anaes. Soc. J. 15, 111–117 (1968). https://doi.org/10.1007/BF03005718
Issue Date:
DOI: https://doi.org/10.1007/BF03005718