Amitriptyline
Mechanism of action: Amitriptyline is a non-selective re-uptake inhibitor of norepinephrine and serotonin. It also displays cross-reactivity with opioid, cholinergic and adrenergic receptors.
Presentation: tablet, oral solution
Suggested initial dose: 10mg at night for adults over 50kg up to a usual maximum of 75mg. The dose for neuropathic pain is lower than the anti-depressant dose. Amitriptyline is particularly dangerous in overdose.
It usually takes 3-7 days for the analgesic effect to become clinically beneficial.
Oral absorption: Bioavailability of 33-62% due to first pass metabolism
Protein binding: 96% bound to plasma proteins
Metabolism: Amitriptyline undergoes hepatic oxidative metabolism by cytochrome P450s, with CYP2D6 producing inactive metabolites. CYP2C19 and CYP3A4 are responsible for the demethylation of amitriptyline to the very active metabolite, nortriptyline.
Elimination: mostly excreted in the urine as metabolites and conjugates. Small amounts are excreted in the faeces.
Half-life: 10-28 hours for amitriptyline, and 16-30 hours for nortriptyline
Common side effects include: sedation, dry mouth, blurred vision, weight gain, urinary retention
Important cautions include: cardiac disease, glaucoma, suicide risk, seizure disorder and concomitant use of tramadol, due to the risk of serotonin syndrome.
Further prescribing information (side effects, contraindications, interactions):