Tramadol: Pharm

Tramadol is a synthetic centrally acting opioid receptor agonist with weak mu receptor affinity and even weaker kappa and delta affinity. Tramadol and its active metabolite (O-desmethyltramadol) binds to μ-opioid receptors in the central nervous system 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 selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs). 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.

Oral bioavailability 75%

Onset: within 1 hour

Time to peak:

Immediate release: ~2 hours

Extended release: ConZip™: ~10-12 hours

Tridural™: ~4 hours; Durela™

Ultram® ER: ~12 hours

Tramadol undergoes hepatic metabolism via demethylation, glucuronidation and sulfation. It is excreted in urine.

Excretion: Urine (30% as unchanged drug; 60% as metabolites)

There is increased risk of serotonin syndrome and a reduced seizure threshold if a patient is taking other serotonergic medications, most notably MAOIs and TCAs, but also SSRIs, SNRIs, triptans, antipsychotics, anticonvulsants, antiparkinsonian medications, St John’s wort, and dextromethorphan.