Pharmacology: Pharmacodynamics: The combination of Tramadol HCl and Paracetamol provides double analgesic benefits for moderate to severe pain. Tramadol is an opioid analgesic which acts on the central nervous system to block the transmission of pain signals. Tramadol mimics the action of the naturally occurring pain relieving chemical, endorphins found in the brain and spinal cord. Endorphin reduces pain by combining with the opioid receptors. This blocks the transmission of pain signals sent by the nerves to the brain. Tramadol also has noradrenergic and serotonergic properties that may contribute to its analgesic activity. Tramadol also works by enhancing the activity of neurotransmitters serotonin and noradrenaline in the brain and spinal cord. These are chemical compounds that act as chemical messengers between the nerve cells which also help relieve pain.
Paracetamol is a para-aminophenol derivative which has analgesic and antipyretic properties and a weak anti-inflammatory activity. Paracetamol relieves pain by blocking the production of prostaglandin, the chemical that causes pain, through the inhibition of the enzyme cyclooxygenase. The combination of tramadol and paracetamol provides synergistic effect to relieve moderate to severe pain.
Pharmacokinetics: Tramadol is readily absorbed following oral administration but is subject to first-pass metabolism. Tramadol is metabolized 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 and is widely distributed, crosses the placenta, and appears in small amounts in breast milk. The elimination half-life following oral administration is about 6 hours.
Paracetamol is readily absorbed from the gastrointestinal tract with peak plasma concentrations occurring about 10 to 60 mins after oral doses. Paracetamol is distributed into most body tissues. It crosses the placenta and is present 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.