| Class | Alpha antagonist |
|---|---|
| Chemistry |
Haloalkylamine |
| Routes of administration |
Oral only |
| Absorption |
Bioavailability is about 20-30%, mainly because of incomplete and variable gut absoprtion |
| Solubility |
Highly lipid soluble, but poorly water-soluble. pKa = 7.97 |
| Distribution |
The VOD is massive because of the high lipid solubility and protein binding, but nobody seems to have a number for it in the literature |
| Metabolism |
Hepatic metabolism into inactive metabolites (very slow, as little free drug is avalable in the circulation) |
| Elimination |
Inactive metabolites are eliminated in the bile and urine. Half life is about 24 hrs. |
| Time course of action |
Onset of effect is about 1-2 hrs; however the duration of effect is 3-4 days, as this is roughly how long it takes you to synthesise new alpha-receptors |
| Target receptor |
Slighly more selective for alpha-1 adrenoceptors, vs. alpha-2 receptors |
| Mechanism of action |
The antihypertensive effect is as a NON-competitive (irreversable) alpha-1 adrenergic receptor blocker. By covalently 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 |
Postural hypotension, tachycardia, arrhythmias, drowsiness, fatigue, inhibition of ejaculation, nasal congestion, miosis, and dry mouth. Also penetrates the CNS, causing stimulation, nausea, vomiting, motor excitation, and occasionally seizures. |
| Literature reference |
Gruetter, Carl A. "Phenoxybenzamine." (2007): 1-4. |
| CICM details of understanding | Not specifically listed in the CICM syllabus |
| Mentioned around Deranged Physiology | |
| Related SAQs |