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The Clinical Effects of Morphine Pharmacology
  1. Laurence E. Mather, Ph.D., F.A.N.Z.C.A.
  1. Department of Anaesthesia and Pain Management, University of Sydney at Royal North Shore Hospital, St. Leonards, Australia
  1. Reprint requests: Laurence E. Mather, Ph.D., F.A.N.Z.C.A., Department of Anaesthesia and Pain Management, University of Sydney at Royal North Shore Hospital, St. Leonards, NSW 2065, Australia.

Abstract

Background and Objectives. The literature is replete with studies of morphine. It is not surprising that some viewpoints expressed tend to be often repeated without critical analysis. The goal of this lecture is to probe some commonly held viewpoints about the pharmacology of morphine. This involves retracing some of its history, re-examining its physicochemical nature, re-evaluating its physiologic disposition and the pharmacologic activity of its metabolites.

Methods. The background material selected for inclusion consists of historic pharmacologic secondary sources, selections from the recent primary literature on morphine pharmacokinetics and metabolism, and vignettes from the author's personal research in progress with colleagues in Australia.

Results. The author's perspective is that of a chemical pharmacologist with more than a passing interest in pharmacokinetics. The synthesis evaluates the therapeutic consequences of the pharmacologic aspects chosen.

Conclusions. Morphine in various forms has been used successfully in the alleviation of pain for at least several millenia but it is only relatively recently that a rationale for its action has been found. Morphine is a relatively poorly lipophilic opioid but equilibrates with tissue of the brain relatively easily. While the metabolism of morphine occurs in the liver, it is metabolized in the kidneys and brain as well. The clearance of morphine is not notably decreased by renal dysfunction, but clearance of its glucuronide metabolites is decreased markedly. While the metabolites produced may be shown to be pharmacologically active in particular experimental preparations, it is not yet certain that they contribute pharmacologically after systemic administration of morphine in experimental animals or humans with generally normal physiology.

  • morphine
  • pharmacokinetics
  • opioid
  • metabolites

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Footnotes

  • Presented at the 19th Annual Meeting of the American Society of Regional Anesthesia, Chicago, Illinois, April 9, 1994.

    Financial support from the National Health and Medical Research Council of Australia.

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