Tramadol

Uses

Chemical

Tramadol is a synthetic opiod of the aminocyclohexonal group and a phenylpiperadine anaolgue of codeine. It consists of a racemic mixture of two enantonmers.

Presentation

As a clear aqueous solution containing 50mg/ml or as tables containing 50, 100, 150, 200, 300, 400mg of tramadol hydrochloride

Main Actions

Centrally mediated analgesia

Mode of action

Non-selective agonist at μ, κ and δ receptors (with a relatively higher affinity for μ receptors. Also inhibits neuronal reuptake of noradrenaline and serotonin (5-HT) and also enhances serotonin release. These actions activate the descending inhibitory pathway in the CNS. He two enantomers appear to have different effects. (+)Tramadol affects μ-receptors and 5-HT reuptake/release, while (-)Tramadol inhibits NA release.

Route of administration / Dose

Adult dose 50-100mg 4-6 hourly by all routes. Paediatric dose is 1-2mg/kg 4-6 hourly (not licensed in children under 12).

Effects

CVS - none

Resp - Resp. rate, minute volume and PaCO2 remain essentially unchanged fllowing iv administration of therapeutic doses.

Analgesic properties similar to pethidine. Analgesic properties only 30% reversed by naloxone.

Toxicity / Side effects

Nausea, dizziness, sedation and diaphoresis. Potential for tolerance appears low

Kinetics

Bioavailability following oral absorption is 68% rising to 90-100% on repeat dosing.

Distribution

20% protein bound in the plasma VD is 2.9-4.37 l/kg. 80% of administered dose crosses the placenta.

Metabolism

85% undergoes hepatic demethylation and conjugation. One metabolite, O-demethyltramadol, is active (2-4 times the analgesic potency of tramadol and T½ of 9hrs - caution n renal/hepatic impairement).

Excretion

90% excreted in the urine and 10% in faeces. Clearance 6.7-10.1 ml/min with an elimination T½ of 270-450 mins. This is doubled in patients with renal or hepatic impairement (increase doe-interval to 12hrs)

Special points

Not licensed for intra-operative use - may be assocaited with increased recal.

Appears to be effective in treating post-op shivering.

Precipitates when mixed with diazepam or midazolam. Only slowy cleared by haeodialysis or haemofiltration.

Contraindicated in association with MAOIs and reduced efficacy with carbemazipine.