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Tramadol Side Effects and MetabolismAdverse Tramadol side effects - WarningThe most commonly reported adverse Tramadol side effects and reactions are nausea / sickness, vomiting and sweating. Drowsiness has also been reported, although it is believed to be less of an issue compared to other opioids. Seizures have been reported in humans receiving excessive single oral doses (700 mg) or large intravenous doses (300 mg). An Australian study finds that of 97 confirmed new-onset seizures, 8 were associated with Tramadol, and that in the authors' First Seizure Clinic, "Tramadol is the most frequently suspected cause of provoked seizures" (Labate 2005). Dosages of coumadin / warfarin may need to be reduced for anticoagulated patients to avoid bleeding complications. MetabolismTramadol undergoes hepatic metabolism via the cytochrome P450 isozyme CYP2D6, being O- and N-demethylated to 5 different metabolites. Of these, M1 is the most significant since it has 200 times the µ-affinity of (+)-tramadol, and furthermore has an elimination half-life of 9 hours compared to 6 hours for tramadol itself. In the 6% of the population who have slow CYP2D6 activity, there is therefore a slightly reduced analgesic effect. Phase II hepatic / liver metabolism renders the metabolites water-soluble and they are excreted by the kidneys. Thus reduced doses may be used in renal / kidney and hepatic / liver impairment. |
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