Pharmacology Notes

Tramadol is a synthetic weak mu-opioid agonist that also enhances noradrenergic and serotonergic inhibition of nociceptive transmission. Advantages include analgesia with minimal sedation or respiratory depression, reduced gastrointestinal adverse effects, and the availability of oral and parenteral formulations. Tramadol is converted to an active metabolite, by cytochrome P450 2D6. This pathway is absent in 7% to 10% of Caucasians and 1% to 2% of Asians. These patients will receive a reduced analgesic benefit from tramadol. Tramadol has limited analgesic activity, and if the doses are increased to try to get better analgesia, toxicity is likely. Tramadol is not recommended for use in palliative care.

Oral administration using the immediate-release capsule formulation requires dosing every 4 to 8 hours; the modified-release tablet formulation can be given twice daily.

Tramadol can cause dizziness, sweating, dry mouth, nausea and postural hypotension in some patients. It can induce seizures, even within the therapeutic dose range. This risk increases in patients with pre-existing epilepsy or a recognised risk for seizures, or when tramadol is prescribed with other drugs that lower seizure threshold (eg tricyclic antidepressants, selective serotonin reuptake inhibitors [SSRIs], some antipsychotics, quinolones). Tramadol should be used with caution in patients taking serotonergic agents (eg SSRIs, mirtazapine, venlafaxine, selegiline, St John’s wort) due to the risk of the serotonin syndrome. Combined use with monoamine oxidase inhibitors [MAOIs] (including moclobemide) causes central nervous system excitation or depression, hypertension or hypotension. Avoid use within two days of treatment with moclobemide and within 14 days of treatment with irreversible MAOIs. As tramadol is metabolised by the cytochrome P450 2D6 isoenzyme, potential drug interactions should be considered.