Tramadol is an opioid analgesic that acts centrally. It is a pure non-selective agonist in μ, δ and κ opioid receptors with a greater affinity for the μ receptor thereby altering the perception of pain and the emotional response to it.
Mu receptors are widely distributed throughout the CNS, especially in the limbic system, thalamus, striatum, hypothalamus and midbrain, as well as in laminae I, II, IV and V of the spinal cord. Kappa receptors are located mainly in the medulla and in the cerebral cortex.
Other mechanisms that contribute to its analgesic effect are inhibition of neuronal reuptake of norepinephrine and serotonin.
Tramadol has an antitussive effect. Gastrointestinal motility is not affected. The effects of tramadol on major, minor circulation and on the heart are scarce and clinically unimportant, so there is no limitation for its use in coronary heart disease accompanied by pain. At therapeutic doses it does not cause alterations in the respiratory system. The potency of tramadol is reported to be 1/10 to 1/6 of morphine.
More than 90% of tramadol hydrochloride is absorbed after administration. The absolute bioavailability is about 70% regardless of concomitant food intake.
The difference between tramadol absorbed and non-metabolized available is probably due to the low effect of the first step. The effect of the first step, after oral administration is 30% maximum.
After oral administration of 100 mg in liquid form, the peak plasma concentration Cmax is 309 ± 90 ng / ml after 1.2 hours. The plasma protein binding is around 20%. Tramadol crosses the blood-brain and placental barriers. Very small amounts of the substance and its O-demethylated derivative are found in breast milk (0.1% of the applied dose).
The elimination half-life is approximately 6 hours, regardless of the route of administration. In patients older than 75 years it can be prolonged by a factor of approximately 1.4. Tramadol is mainly metabolized by means of N- and O-demethylation and conjugation of O-demethylation products with glucuronic acid. Only O-desmethyltramadol is pharmacologically active, the half-life of metabolites is similar to that of the substance of origin. Tramadol and its metabolites are almost completely excreted by the kidneys. In cases of renal and hepatic impairment, the half-life may be slightly prolonged.