| Class | Monoamine reuptake inhibitor |
|---|---|
| Chemistry |
guanidine |
| Routes of administration |
Oral and, occasionally, IV |
| Absorption |
Bioavailability 3-50%, absorption is variable |
| Solubility |
Poor solubility in water; highly lipid soluble; penetrates the blood-brain barrier |
| Distribution |
VOD unknown; presumably large, as it binds irreversibly to VMAT targets and to red blood cells |
| Metabolism |
Hepatic metabolism accounts for 50% of elimination |
| Elimination |
Half of the dose is eliminated unchanged in the urine. Elimination half-life is 5 days, but plasma distribution half-life is much more rapid, ~ 10 minutes |
| Time course of action |
Long acting; after a loading dose, can be dosed daily |
| Target receptor |
VMAT-2 (vesicular monoamine transporter-2) |
| Mechanism of action |
Irreversibly blocks VMAT-2 in the adrenergic neurotransmission pathway. This results in catecholamines and serotonin lingering in the cytoplasm where they are destroyed by intraneuronal monoamine oxidase, thereby causing the depletion of catecholamine and serotonin stores in central and peripheral nerve terminals |
| Clinical effects |
Hypotension, bradycardia,unpooposed parasympathetic excess(eg. diarrhoea), volume expansion, oedema, but interestingly little in the way of CNS effects. |
| Literature reference |
Lukas (1974) |
| CICM details of understanding | Not specifically listed in the CICM syllabus |
| Mentioned around Deranged Physiology | |
| Related SAQs |