Mechanism of Action of Prazosin
Prazosin is a selective alpha-1 adrenergic receptor antagonist that reduces blood pressure by blocking postsynaptic alpha-1 receptors, causing vasodilation primarily at the level of resistance vessels (arterioles). 1
Primary Mechanism
- Prazosin selectively blocks alpha-1 adrenergic receptors, which are predominantly located in vascular smooth muscle 2
- This blockade prevents norepinephrine from binding to these receptors, inhibiting sympathetically mediated vasoconstriction 3
- The primary site of action is at the resistance vessels (arterioles), leading to decreased peripheral vascular resistance 1
- Unlike non-selective alpha blockers, prazosin has minimal effect on presynaptic alpha-2 receptors, preserving the negative feedback control of norepinephrine release 2
Hemodynamic Effects
- Prazosin causes a decrease in total peripheral resistance without significantly affecting cardiac output 1
- The drug produces balanced reduction in both arteriolar and venous tone 3
- Unlike conventional alpha-blockers or direct vasodilators, prazosin typically does not cause reflex tachycardia 1, 4
- The absence of significant reflex tachycardia is attributed to its selective alpha-1 blockade that preserves presynaptic alpha-2 receptor function 2
Pharmacological Specificity
- Prazosin exhibits high selectivity for alpha-1 receptors with minimal effect on alpha-2 receptors 2
- The drug does not possess direct vasodilator properties at therapeutic concentrations - it only relaxes vessels through alpha-1 receptor blockade 5
- Prazosin does not affect contractile responses to other vasoconstrictors like potassium chloride or serotonin 5
- It has no measurable negative chronotropic effect on the heart 1
Clinical Implications
- Prazosin's selective alpha-1 blockade makes it effective for both hypertension and BPH 6
- The drug is also used for PTSD-associated nightmares due to its effects on alpha-1 receptors in the central nervous system 6
- Prazosin's mechanism allows for effective blood pressure reduction without significantly increasing heart rate, plasma renin activity, or causing fluid retention 1, 3
Pharmacokinetics
- After oral administration, plasma concentrations peak at approximately 3 hours 1
- The drug has a plasma half-life of 2-3 hours 1
- Prazosin is highly protein-bound in plasma 1
- It is extensively metabolized, primarily by demethylation and conjugation 1
- Excretion occurs mainly via bile and feces 1
Important Considerations
- First-dose phenomenon: Prazosin can cause significant orthostatic hypotension, especially after the initial dose 7
- Elderly patients are at higher risk for prazosin-induced hypotension 7
- Patients on concurrent antihypertensive medications have increased risk of hypotension 7
- Dosing typically starts low (1 mg at bedtime) with gradual titration to minimize orthostatic effects 7