Tramadin Mechanism of Action

Tramadol is a centrally acting analgesic with binding to specific opioid receptors. It is a non-selective, pure agonist at mu (μ), delta (d) and kappa (k) opioid receptors with a higher affinity for the μ receptor. Other mechanisms, which may contribute to its analgesic effect, are inhibition of neuronal re-uptake of noradrenaline and serotonin. Tramadol is well absorbed after oral or rectal administration, with an absorption half-life (t_½ka) 0.38 ± 0.18 hours, leading to an analgesic effect lasting for up to 9 hours. The parenteral form of tramadol has a more rapid onset of action. The mean systemic bioavailability is 68%. Tramadol hydrochloride crosses the blood-brain barrier and placental barrier. Only very small amounts are excreted in breast milk unchanged or as the metabolite M1 (tramadol hydrochloride approximately 0.1%, M1 approximately 0.02% of the IV Dose. The elimination half-life is 5 to 7 hours. Tramadol is mainly metabolized in the liver (90%).
Tramadol hydrochloride and its metabolites are almost completely excreted by the renal route (95%).
Biliary excretion of these components is quantitatively insignificant and is therefore subject to hepatic metabolism and renal elimination. The terminal half-life (t_½β) is likely to be prolonged in impaired hepatic or renal function. The increase in the (t_½β) values is relatively low if at least one of these organs is functioning normally. In patients with liver cirrhosis, the mean t_½β of tramadol was 13.3 ± 4.9 h, t_½β/M1 18.5 ± 9.4 h; in patients with renal insufficiency (creatinine clearance ≤5 mL/min) the values were 11.0 ± 3.2 h (tramadol) and 16.9 ± 3.0 h (M1) respectively.
There are sex differences in the pharmacokinetic parameters of tramadol. The absolute bioavailability was 73% in males and 79% in females. Plasma clearance was 6.4 mL/min/kg in males and 5.73 mL/min/kg in females following a 100 mg IV dose. Following a single oral dose and after adjusting for bodyweight, females had a 12% higher peak concentration time curve compared to males. The clinical significance of these differences is unknown.