| Class | Alpha-2 agonist |
|---|---|
| Chemistry |
phenylalanine derivative |
| Routes of administration |
Oral only |
| Absorption |
Bioavailability is 25% (range 8 to 62%). |
| Solubility |
pKa 9.85 |
| Distribution |
Less than 15% protein-bound; small VOD, 0.6L/kg |
| Metabolism |
Metabolised in the liver into methyldopamine and multiple other metabolic byproducts, of which many are active(in fact more active than the parent compound |
| Elimination |
Up to 50% of the dose is cleared renally as unchanged drug, leading to accumulation in renal failure. Half-life is about 1-2hrs |
| Time course of action |
Onset of action is over 1-2 hrs, and the duration of effect is about 10 hrs (i.e. needs twice daily dosing) |
| Target receptor |
Presynaptic alpha-2 receptors |
| Mechanism of action |
Central alpha-2 agonist effect decreases sympathetic outflow by presynaptic downregulation of noradrenaline release. Apart from this, methyldopa and its metabolites (methyldopamine and methylnoradrenaline) interfere with neurotransmission and neurotransmitter synthesis |
| Clinical effects |
Class effects (bradycardia, decreased blood pressure), as well as depression and sedation. Also, can cause haemolytic anaemia and drug-induced lupus |
| Literature reference |
TGA PI for Aldomet |
| CICM details of understanding | Not specifically listed in the CICM syllabus |
| Mentioned around Deranged Physiology | |
| Related SAQs |