Lotram Plus Mechanism of Action

Analgesic.
Pharmacology: Tramadol Hydrochloride: Tramadol Hydrochloride is a centrally acting analgesic. It is a non selective pure agonist at mu, delta and kappa opioid receptors with a higher affinity for the receptor. Other mechanisms which may contribute to its analgesic effect are inhibition of neuronial reuptake of noradrenaline and enhancement of serotonin release.
Paracetamol: The mechanism of analgesic action has not been fully determined. Paracetamol may act predominantly by inhibiting prostaglandin synthesis in the central nervous system (CNS) and to a lesser extent, through a peripheral action by blocking pain-impulse generation.
The peripheral action may also be due to inhibition of prostaglandin synthesis or to inhibition of the synthesis or actions of other substances that sensitize pain receptors to mechanical or chemical stimulation.
Paracetamol probably produces antipyresis by acting centrally on the hypothalamic heat regulation center to produce peripheral vasodilation resulting in increased blood flow through the skin, sweating and heat loss. The central action probably involves inhibition of prostaglandin synthesis in the hypothalamus.
Pharmacokinetics: Tramadol: Tramadol is readily absorbed after oral doses but is subject to some first-pass metabolism. Mean absolute bioavailability is about 70 to 75% after oral use and 100% after intramuscular injection.
Plasma protein binding is about 20%. Tramadol is metabolised by N-and O-demethylation via the cytochrome P450 isoenzymes CYP3A4 and CYP2D6 and glucuronidation or sulfation in the liver. The metabolite O-desmethyltramadol is pharmacologically active. Tramadol is excreted mainly in the urine, predominantly as metabolites. Tramadol is widely distributed, crosses the placenta, and appears in small amounts in breastmilk. The elimination half-life is about 6 hours.
Paracetamol: Paracetamol is readily absorbed from the gastrointestinal tract with peak plasma concentrations occurring about 10 to 60 minutes after oral doses. Paracetamol is distributed into most body tissues. It crosses the placenta and is present in breast milk. Plasma protein binding is negligible at usual therapeutic concentrations but increases with increasing concentrations. The elimination half-life of Paracetamol varies from about 1 to 3 hours.
Paracetamol is metabolised mainly in the liver and excreted in the urine mainly as the glucuronide and sulfate conjugates. Less than 5% is excreted as unchanged Paracetamol. A minor hydroxylated metabolite (N-acetyl-p-benzoquinoneimine), is usually produced in very small amounts by cytochrome P450 isoenzymes (mainly CYP2E1 and CYP3A4) in the liver and kidney. It is usually detoxified by conjugation with glutathione but may accumulate after Paracetamol overdosage and cause tissue damage.