Ketamine
PAIN TEAM PRESCRIPTION ONLY
Mechanism of action: Ketamine is a phencyclidine derivative which is an antagonist of the N-methyl-D-aspartate (NMDA) receptor. It has two optical isomers: S-ketamine has a stronger affinity for the NMDA receptor producing an analgesic and anaesthetic effect four times stronger than R-ketamine, and twice as strong as the racemic mixture. Ketamine also stimulates noradrenergic neurones and inhibits the reuptake of norepinephrine, dopamine and serotonin, which accounts for the hyperadrenergic state it produces. The psychic effects may be due to inhibition of cholinergic neurones in the prefrontal cortex.
It has a role in managing complex acute pain and has an antihyperalgesic effect. It has also been used in treating drug-resistant depression.
Presentation: oral solution, solution for injection (BEWARE: various strengths available)
Suggested initial dose: 25mg orally 6 hourly for adults over 50kg with complex pain and normal hepatic and renal function. PAIN TEAM PRESCRIPTION ONLY
Higher doses must be weaned and not stopped abruptly before patient discharge. Ketamine must NOT be given as a TTO.
Absorption: Poor oral bioavailability of 8-24% after first pass metabolism. Norketamine, the major metabolite of ketamine may also contribute to analgesia. It has an analgesic potency of 20-30% of ketamine and, after oral intake, norketamine concentrations are much higher than the parent drug.
Bioavailability after intranasal administration is around 50%.
Protein binding: 10-30% protein bound
Metabolism: Ketamine undergoes oxidative metabolism by CYP3A4 and CYP2B6 to norketamine. Its systemic clearance is high and equates to hepatic blood flow. Patients with decreased liver blood flow will have reduced clearance and increased oral bioavailability.
Elimination: Most of the dose is excreted in urine, mainly in the form of metabolites, while some is excreted in faeces.
Half-life: 2-4 hours
Further prescribing information (side effects, contraindications, interactions):