STEPTRACKERPHARMACOLOGY | AUTONOMIC | HIGH-YIELD REVIEW

α-Blockers & α2-Agonists

Two ways to lower sympathetic vascular tone: block α1 at the vessel, or turn down sympathetic outflow in the brainstem with α2 agonists.

FOCUS ON
Nonselective α-blockers: phenoxybenzamine (irreversible) — pheochromocytoma before surgery (α before β); phentolamine (reversible) — catecholamine crisis, MAOI–tyramine crisis, extravasation of norepinephrine. Reflex tachycardia is common. α1-selective (-osin): prazosin, terazosin, doxazosin — BPH and hypertension, prazosin for PTSD nightmares; tamsulosin (α1A, prostate) — BPH with little BP effect. Adverse: first-dose orthostatic hypotension, dizziness, floppy-iris syndrome (tamsulosin). α2-selective blocker: mirtazapine (antidepressant). α2 agonists: clonidine, guanfacine (hypertension, ADHD, Tourette, opioid/alcohol withdrawal symptoms); rebound hypertension on abrupt stop; methyldopa (pregnancy hypertension; Coombs-positive hemolysis); dexmedetomidine (ICU sedation); tizanidine (spasticity); brimonidine, apraclonidine (glaucoma).
DRUG
MECHANISM
USE
ADVERSE · NOTES
Phenoxybenzamine
Irreversible nonselective α-blocker
Pheochromocytoma (preoperative)
Orthostasis, reflex tachycardia · start α before β
Phentolamine
Reversible nonselective α-blocker
Hypertensive crisis from cocaine, MAOI + tyramine, NE extravasation
Reflex tachycardia
Prazosin · terazosin · doxazosin
α1-selective
Hypertension, BPH, PTSD nightmares (prazosin)
First-dose syncope · give at bedtime
Tamsulosin · silodosin
α1A-selective (prostate, bladder neck)
BPH, ureteral stone passage
Intraoperative floppy iris during cataract surgery, ejaculatory dysfunction
Mirtazapine
α2 antagonist (↑ NE and 5-HT release), H1 blocker
Depression with insomnia and weight loss
Sedation, ↑ appetite, weight gain
Clonidine
Central α2 agonist → ↓ sympathetic outflow
Hypertension (urgency), ADHD, Tourette, withdrawal symptoms, hot flashes
Sedation, dry mouth, bradycardia · rebound hypertension if stopped abruptly
Guanfacine
α2A agonist
ADHD, hypertension
Milder rebound
Methyldopa
Converted to α-methyl-NE (central α2 agonist)
Hypertension in pregnancy
Positive direct Coombs test (warm hemolytic anemia), hepatitis, drug-induced lupus
Dexmedetomidine
Central α2 agonist
ICU and procedural sedation without respiratory depression
Bradycardia, hypotension
Tizanidine
Central α2 agonist
Spasticity (MS, spinal injury)
Hypotension, sedation · CYP1A2 (ciprofloxacin ↑ levels)
Brimonidine · apraclonidine
Ocular α2 agonists → ↓ aqueous humor
Open-angle glaucoma
Blurred vision, ocular allergy

Mechanism — why α before β in pheochromocytoma

Tumor floods α and β receptors
→
β-block firstLose β2 vasodilation → unopposed α1 → hypertensive crisis
Phenoxybenzamine first(10–14 days)
→
Then β-blockerfor reflex tachycardia
→
Surgery

α1 vs α2 drugs

ACTION
α1
α2
Agonist
Phenylephrine, midodrine
Clonidine, methyldopa
Antagonist
Prazosin, tamsulosin
Mirtazapine
Agonist effect on BP
↑
↓ (central)

How it's tested

COMMON CONFUSIONα2 agonists lower BP by acting centrally; α1 agonists raise BP by acting on vessels — same "α" letter, opposite results.
THE TRAPStopping clonidine suddenly → rebound sympathetic surge with severe hypertension; taper it.
YOUR APPROACHIndication → site (vessel, prostate, brainstem) → selectivity → expected side effect.

If you see… think…

Pheochromocytoma before surgery → phenoxybenzamine
Hypertensive crisis after cheese on an MAOI → phentolamine
Fainting after the first BPH pill → α1-blocker first-dose effect
BPH with minimal BP effect → tamsulosin
Floppy iris during cataract surgery → tamsulosin
Nightmares in PTSD → prazosin
Hypertension in pregnancy, positive Coombs → methyldopa
Severe hypertension after stopping a BP drug → clonidine rebound
ICU sedation without respiratory depression → dexmedetomidine
Antidepressant that blocks α2 → mirtazapine