Mather L E
Department of Anaesthesia and Pain Management, University of Sydney, Royal North Shore Hospital, St. Leonards, Australia.
Reg Anesth. 1995 Jul-Aug;20(4):263-82.
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.
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.
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.
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.
关于吗啡的研究在文献中极为丰富。因此，一些观点往往未经批判性分析就被反复提及，这并不奇怪。本次讲座的目的是探究一些关于吗啡药理学的普遍观点。这涉及追溯其部分历史、重新审视其物理化学性质、重新评估其生理处置以及其代谢产物的药理活性。
所选的背景材料包括历史性药理学二手资料、近期关于吗啡药代动力学和代谢的一手文献选集，以及作者与澳大利亚同事正在进行的个人研究中的案例。
作者的观点是一位对药代动力学有着浓厚兴趣的化学药理学家的观点。本综述评估了所选药理学方面的治疗后果。
各种形式的吗啡已成功用于缓解疼痛至少数千年，但直到最近才找到其作用的理论依据。吗啡是一种脂溶性相对较差的阿片类药物，但相对容易与脑组织达到平衡。虽然吗啡在肝脏中代谢，但在肾脏和大脑中也会代谢。肾功能不全并不会显著降低吗啡的清除率，但其葡萄糖醛酸代谢产物的清除率则会显著降低。虽然在特定实验制剂中所产生的代谢产物可能显示出药理活性，但在生理功能基本正常的实验动物或人类中，全身性给予吗啡后，这些代谢产物是否具有药理作用尚不确定。
