U01.05.026 α-blockers

α-Blockers are a class of drugs that inhibit alpha-adrenergic receptors, affecting vascular tone, smooth muscle contraction, and neurotransmitter release. Their applications range from treating hypertension to managing specific conditions like pheochromocytoma and benign prostatic hyperplasia (BPH).

Categories of α-Blockers

Type	Drugs	Mechanism	Applications	Adverse Effects
Nonselective	Phenoxybenzamine	Irreversible α1 and α2	Pheochromocytoma (preoperative to prevent catecholamine crisis)	Orthostatic hypotension, reflex tachycardia
	Phentolamine	Reversible α1 and α2	MAO inhibitor-associated hypertensive crisis; cocaine-induced hypertension (2nd line)	Same as phenoxybenzamine
α1-selective	Prazosin, Terazosin,	Block α1 receptors	BPH (urinary symptoms); PTSD (prazosin); hypertension (except tamsulosin)	First-dose orthostatic hypotension, dizziness, headache
	Doxazosin, Tamsulosin
α2-selective	Mirtazapine	Block α2 receptors	Depression	Sedation, increased appetite, increased serum cholesterol

Pharmacological Insights

Effects of α-Blockade on Adrenergic Responses

Epinephrine (mixed α and β agonist):
- Before α-blockade: Net pressor effect (increase in mean arterial pressure due to α1-mediated vasoconstriction).
- After α-blockade: Reversal to net depressor effect (β2-mediated vasodilation predominates).
Phenylephrine (pure α-agonist):
- Before and after α-blockade: Net pressor effect persists; no reversal as β2 effects are absent.

Condition	Heart Rate	Blood Pressure	Explanation
Before α-blockade	Reflex bradycardia	Increased (MAP, systolic)	α1-mediated vasoconstriction
After α-blockade	Reflex tachycardia	Decreased (MAP, diastolic)	Unopposed β2-mediated vasodilation

Clinical Notes for USMLE Step 1

Key Applications

Phenoxybenzamine: Preoperative management of pheochromocytoma.
Phentolamine: Reversal of hypertensive crisis in MAO inhibitor patients or cocaine-induced emergencies.
Prazosin: Effective for PTSD-associated nightmares.

Common Side Effects

Orthostatic Hypotension: Especially pronounced with first doses of α1 blockers.
Reflex Tachycardia: More common with nonselective α-blockers due to unopposed β stimulation.

Points to Remember

Nonselective α-blockers: Useful in emergencies but prone to significant cardiovascular side effects.
Selective α1-blockers: First-line treatment for BPH and hypertension; monitor for first-dose effects.
α2-selective blocker (Mirtazapine): Primarily used for depression; notable for sedative and appetite-stimulating effects.
Epinephrine Reversal: A hallmark of α-blockade, important to understand for USMLE pharmacology questions.

Visual Understanding: Response Patterns

Drug	Response Before α-Blockade	Response After α-Blockade	Key Feature
Epinephrine	Increased MAP (α1 > β2)	Decreased MAP (β2 > α1)	Exhibits “reversal” with blockade
Phenylephrine	Increased MAP (pure α1)	Suppressed response	No reversal as it lacks β activity

Bibliography

Katzung BG, Masters SB, Trevor AJ. Basic & Clinical Pharmacology.
Brunton LL, Knollmann BC, Hilal-Dandan R. Goodman & Gilman’s: The Pharmacological Basis of Therapeutics.
USMLE-Rx. First Aid for the USMLE Step 1.

USMLE Step 1 Review Series

Curriculum