• Jörn Lötsch.
• Pharmazentrum Frankfurt, Institute of Clinical Pharmacology, Johann Wolfgang Goethe-University Hospital, Frankfurt, Germany.
• J Pain Symptom Manage. 2005 May 1;29(5 Suppl):S10-24.

AbstractThe 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.

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