Lötsch Jörn
Pharmazentrum Frankfurt, Institute of Clinical Pharmacology, Johann Wolfgang Goethe-University Hospital, Frankfurt, Germany.
J Pain Symptom Manage. 2005 May;29(5 Suppl):S10-24. doi: 10.1016/j.jpainsymman.2005.01.004.
The metabolism of opioids closely relates to their chemical structure. Opioids are subject to O-dealkylation, N-dealkylation, ketoreduction, or deacetylation leading to phase-I metabolites. By glucuronidation or sulfatation, phase-II metabolites are formed. Some metabolites of opioids have an activity themselves and contribute to the effects of the parent compound. This can go as far that the main clinical activity is exerted through active metabolites while the parent compounds are only weak agonist at mu-opioid receptors, as in the case of codeine and tilidine. The clinical effects of tramadol also involve an important contribution of its active metabolite. With morphine, the active metabolite morphine-6-glucuronide exerts important clinical opioid effects when it accumulates in the plasma of patients with renal failure. However, after short-term administration of morphine, its contribution to the central nervous effects of morphine is probably poor. Morphine-6-glucuronide has recently been identified to exert important peripheral opioid effects. By this, it may play an important role in the clinical effects of morphine. Several other opioids, such as meperidine and perhaps also morphine and hydromorphone, produce metabolites with neuroexcitatory effects. In sum, the evidence suggests that the metabolites of several opioids account for an important part of the clinical effects that must be considered in clinical practice.
阿片类药物的代谢与其化学结构密切相关。阿片类药物会发生O-脱烷基化、N-脱烷基化、酮还原或脱乙酰化反应，从而产生I相代谢产物。通过葡萄糖醛酸化或硫酸化作用，会形成II相代谢产物。阿片类药物的一些代谢产物本身具有活性，并对母体化合物的效应有贡献。这种情况甚至可能发展到主要临床活性是通过活性代谢产物发挥的，而母体化合物在μ-阿片受体上只是弱激动剂，如可待因和替利定的情况。曲马多的临床效应也涉及其活性代谢产物的重要作用。对于吗啡，活性代谢产物吗啡-6-葡萄糖醛酸在肾衰竭患者血浆中蓄积时会发挥重要的临床阿片类效应。然而，短期给予吗啡后，其对吗啡中枢神经效应的贡献可能较小。最近发现吗啡-6-葡萄糖醛酸具有重要的外周阿片类效应。由此，它可能在吗啡的临床效应中发挥重要作用。其他几种阿片类药物，如哌替啶，可能还有吗啡和氢吗啡酮，会产生具有神经兴奋作用的代谢产物。总之，证据表明几种阿片类药物的代谢产物在临床效应中占重要部分，在临床实践中必须予以考虑。
