Tramadol – a psychotropic opioid analgesic, belongs to the group of partial opioid receptor agonists. It has a strong analgesic activity, gives a quick and lasting effect. Inferior, however, in activity to morphine at the same doses (respectively, it is used in higher doses). Analgesic effect develops 15-30 minutes after ingestion and lasts up to 6 hours. It is used as a separate drug, as well as in combination with paracetamol.
A synthetic analgesic that has a central action and action on the spinal cord (promotes the opening of K + and Ca2 + ion channels, causes hyperpolarization of the membranes and inhibits the conduction of pain impulses), enhances the effect of sedative drugs. Activates opiate receptors (μ-, Δ-, κ-) on the pre- and postsynaptic membranes of the afferent fibers of the nociceptive system and in the gastrointestinal tract. Slows down the destruction of catecholamines, stabilizes their concentration in the central nervous system.
The affinity of tramadol to opioid receptors is 10 times weaker than that of codeine, and 6000 times weaker than that of morphine, while the severity of analgesic action is only 5-10 times weaker than morphine.
Tramadol is a racemic mixture of 2 enantiomers – dextrorotatory (+) and levogyrate (-), each of which exhibits a different receptor affinity. (+) Tramadol is a selective agonist of mu-opiate receptors, and also selectively inhibits the inverse neuronal seizure of serotonin. (-) Tramadol inhibits the reverse neuronal capture of norepinephrine. Mono-O-desmethyltramadol (M1 metabolite) also selectively stimulates mu-opiate receptors.
In therapeutic doses, it does not significantly affect hemodynamics and respiration, does not alter the pressure in the pulmonary artery, and slightly slows down intestinal motility, without causing constipation. It has some antitussive and sedative effects. Inhibits the respiratory center, stimulates the starting area of the vomiting center, the nucleus of the oculomotor nerve.
With prolonged use may develop tolerance
Absorption – 90%; bioavailability – 68% when administered orally (increased with repeated use), 70% – with rectal administration, with intramuscular administration – 100%. TCmax after ingestion of tablets – 2 hours, when taking drops – 1 hour, with intramuscular administration – 45 minutes, M1 metabolite – 3 hours. Penetrates through the blood-brain barrier and the placenta, 0.1% is excreted in breast milk. The volume of distribution is 203 l with intravenous administration and 306 l with oral administration. Communication with plasma proteins – 20%.
In the liver, it is metabolized by N- and O-demethylation followed by conjugation with glucuronic acid. 11 metabolites were detected, of which mono-O-desmethyltramadol (M1) has pharmacological activity. CYP2D6 isoenzyme is involved in the metabolism of the drug. T1 / 2 in the second phase – 6 h (tramadol), 7.9 h (mono-O-dezmetiltramadol); in patients older than 75 years – 7.4 h (tramadol); in liver cirrhosis – 13.3 ± 4.9 h (tramadol), 18.5 ± 9.4 h (mono-O-dezmetiltramadol), in severe cases – 22.3 h and 36 h, respectively. T1 / 2 in chronic renal failure (CC less than 5 ml / min) – 11 ± 3.2 h (tramadol), 16.9 ± 3 h (mono-O-dezmetiltramadol), in severe cases – 19.5 h and 43.2 h, respectively.
Excreted by the kidneys (25-35% unchanged), the average cumulative rate of renal excretion – 94%. About 7% is excreted through hemodialysis.