Tramadol and its active metabolite (O-desmethyltramadol) binds to μ-opioid receptors in the CNS causing inhibition of ascending pain pathways and altering the perception of and response to pain. Tramadol also inhibits the reuptake of norepinephrine and serotonin, which are neurotransmitters involved in the descending inhibitory pain pathway responsible for pain relief.
Tramadol is indicated for treatment of moderate-to-severe pain in adults. Among specific adverse effects is an increased risk of serotonin syndrome and seizures in patients taking SSRIs, SNRIs, TCAs and MAOI. Compared to other opioid analgesics, tramadol has similar analgesic profile with less respiratory depression and sedative effects.
Metabolism: Extensively hepatic via demethylation (mediated by CYP3A4 and CYP2B6), glucuronidation, and sulfation; has pharmacologically active metabolite formed by CYP2D6 (O-desmethyltramadol). Of note, O-desmethyltramadol is a more potent opioid agonist.
Time to peak: Immediate release: ~2 hours; Extended release: ConZip™: ~10-12 hours, Tridural™: ~4 hours; Durela™, Ultram® ER: ~12 hours
Excretion: Urine (30% as unchanged drug; 60% as metabolites)