tramadol

Tramadol is a prescription analgesic developed as a synthetic, centrally acting opioid. It is indicated for the relief of moderate to moderately severe acute or chronic pain and is available in oral forms, including immediate- and extended-release preparations, as well as injectable formulations. In many countries it is classified as a controlled substance with dispensing restrictions.

Pharmacology and metabolism: Tramadol has a dual mechanism of action. It acts as a weak agonist at the mu-opioid receptor and inhibits the reuptake of norepinephrine and serotonin, contributing to analgesia. The drug’s analgesic effect is augmented by its active metabolite, O-desmethyltramadol (M1), produced mainly by the enzyme CYP2D6. Genetic variation in CYP2D6 can influence both the efficacy and the risk of adverse effects, leading to variability in response among individuals.

Dosing and administration: In adults, typical oral dosing is 50 mg every 4 to 6 hours as needed, with a maximum daily dose often limited to 400 mg. Dosing may require adjustment in hepatic or renal impairment and in older adults. Tramadol is not approved for children under 12 years and should be used with caution in certain pediatric populations and postoperative settings due to the risk of respiratory depression. Higher doses or rapid escalation increase the risk of adverse effects, including seizures.

Safety and adverse effects: Common adverse effects include nausea, constipation, dizziness, drowsiness, and headache. Serious concerns include respiratory depression, particularly with higher doses or in combination with other central nervous system depressants; serotonin syndrome when used with serotonergic drugs; and seizures, especially at high doses or with interacting medications. Long-term use may lead to dependence and withdrawal upon discontinuation.

Regulatory status and notes: Tramadol is a controlled substance in many jurisdictions (for example, Schedule IV in the United States). It should be used under medical supervision, with caution in patients with a history of substance use disorder, epilepsy, or concurrent serotonergic therapy.