| Class | Alpha antagonist |
|---|---|
| Chemistry |
Quinazoline derivative |
| Routes of administration |
Oral only |
| Absorption |
Oral bioavailability is 43-69%; high first pass metabolism. Oral bioavailability is increased in patients with congestive heart failure, because of some unknown mechanism |
| Solubility |
pKa 8.42; slighly water-soluble; also only slightly lipid soluble, but enough that it can cross the blood-brain barrier. |
| Distribution |
Highly protein bound (92-97%). VOD ~ 42L/kg |
| Metabolism |
Hepatic metabolism, primarily by demethylation and conjugation. Of the metabolites, basically everything is excreted in the bile. |
| Elimination |
Half-life is about 2.5 hrs |
| Time course of action |
Relatively slow onset, 1-3 hrs after oral administration. Duration of effect is 6-8hrs |
| Target receptor |
Alpha-1 adrenoceptor |
| Mechanism of action |
Competitive alpha-1 adrenergic receptor blocker: by binding to this Gq-protein-coupled receptor, this drug decreases the activation of phospholipase C, resulting in a decreased concentration of the secondary messengers IP3 and DAG. The result is decreased intracellular calcium availability, which in turn leads to decreased smooth muscle contraction tone. |
| Clinical effects |
Produces systemic vasodilation without affecting heart rate and cardiac output; also produces venodilation; acts as a smooth muscle relaxant at the level of the urethral sphincter, decreasing symptoms of prastatic hypertrophy. Also decreases risk of PTSD. Has been used to manage Rayhaud's phenomenon. Postural hypotension is one of the possible side effects. |
| Literature reference |
TGA PI |
| CICM details of understanding | Not specifically listed in the CICM syllabus |
| Mentioned around Deranged Physiology | |
| Related SAQs |