Alpha Blockers (α-Adrenergic Antagonists)

1. Introduction

Alpha blockers, also known as α-adrenergic antagonists, are a class of drugs that inhibit the stimulation of alpha-adrenergic receptors (α1 and α2) by catecholamines (norepinephrine and epinephrine).
They are primarily used to treat hypertension, benign prostatic hyperplasia (BPH), and certain vascular disorders by inducing vasodilation and smooth muscle relaxation.

Alpha blockers can be selective (α1-specific) or non-selective (blocking both α1 and α2 receptors).

2. Classification

2.1 Non-Selective Alpha Blockers (α1 + α2)

Drug	Use	Characteristics
Phentolamine	Hypertensive emergencies (e.g., pheochromocytoma crisis)	Short-acting, reversible
Phenoxybenzamine	Pheochromocytoma (preoperative management)	Long-acting, irreversible

2.2 Selective Alpha-1 Blockers

Drug	Use	Characteristics
Prazosin	Hypertension, BPH	Short-acting
Terazosin	Hypertension, BPH	Longer half-life
Doxazosin	Hypertension, BPH	Long duration of action
Tamsulosin, Alfuzosin, Silodosin	BPH (urinary symptoms)	Uroselective (α1A receptor preference)

2.3 Selective Alpha-2 Blockers

Drug	Use	Characteristics
Yohimbine	Historically used for erectile dysfunction, orthostatic hypotension	Increases sympathetic outflow; not widely used clinically

3. Mechanism of Action

Alpha blockers inhibit adrenergic receptor-mediated vasoconstriction and smooth muscle contraction.

α1-Blockade:
- Inhibits vasoconstriction → Vasodilation → ↓ Peripheral resistance → ↓ Blood pressure
- Relaxes smooth muscles in bladder neck and prostate → improves urine flow in BPH
α2-Blockade:
- Increases norepinephrine release (via presynaptic receptor blockade) → may cause reflex tachycardia

4. Pharmacodynamics

Cardiovascular effects:
- ↓ Arterial resistance (afterload) and venous tone (preload)
- Reflex tachycardia due to baroreceptor stimulation (especially with non-selective agents)
Genitourinary effects:
- Relaxation of prostate and bladder neck smooth muscle → symptom relief in BPH

5. Pharmacokinetics

Property	Selective α1 Blockers	Non-selective α Blockers
Absorption	Well absorbed orally	Variable (phentolamine parenteral)
Metabolism	Hepatic (CYP450)	Hepatic
Duration	6–24 hours depending on agent	Phenoxybenzamine up to 72 hours
Elimination	Renal and biliary	Renal

6. Clinical Uses

6.1 Hypertension

Prazosin, Terazosin, Doxazosin: Lower blood pressure by vasodilation.
- Often used as add-on therapy, not first-line, due to risk of orthostatic hypotension.

6.2 Benign Prostatic Hyperplasia (BPH)

Tamsulosin, Alfuzosin, Silodosin:
- Selective for α1A-receptors in prostate and bladder neck.
- Improve urine flow and reduce obstructive urinary symptoms.

6.3 Pheochromocytoma

Phenoxybenzamine (long-acting) and Phentolamine (short-acting) are used to control hypertension before surgery and manage catecholamine-induced crises.

6.4 Peripheral Vascular Diseases

Historically used in Raynaud’s disease or frostbite, though now less common.

6.5 Other Uses

Post-traumatic stress disorder (PTSD): Prazosin may reduce nightmares and hyperarousal symptoms.
Erectile dysfunction: Yohimbine (α2-blocker) historically used, though largely replaced by PDE-5 inhibitors.

7. Adverse Effects

System	Adverse Effect	Explanation
Cardiovascular	Postural (orthostatic) hypotension, syncope, reflex tachycardia	Sudden drop in BP upon standing
CNS	Dizziness, fatigue, headache	CNS α1 inhibition
Genitourinary	Retrograde ejaculation (Tamsulosin)	Smooth muscle relaxation
Gastrointestinal	Nausea, diarrhea	α-blockade on GI smooth muscles
Others	Nasal congestion, miosis	Vasodilation and smooth muscle effects

“First-dose phenomenon”: Marked postural hypotension after the first dose of prazosin—patients should take it at bedtime.

8. Drug Interactions

β-blockers: May enhance antihypertensive effect; use cautiously.
PDE-5 inhibitors (e.g., sildenafil): Additive hypotensive effect.
Diuretics and other antihypertensives: Potentiate hypotension.
NSAIDs: May reduce antihypertensive efficacy by sodium retention.

9. Contraindications and Precautions

Contraindications:
- Hypotension or history of syncope
- Hypersensitivity to α-blockers
Caution in:
- Elderly (risk of falls)
- Hepatic impairment
- Volume-depleted patients

10. Clinical Pearls

Prazosin is useful in hypertension and PTSD, but start with low doses.
Tamsulosin is preferred for BPH due to its prostate selectivity and fewer BP effects.
Phenoxybenzamine is essential in pheochromocytoma management pre-surgery.
Avoid abrupt discontinuation; taper gradually to prevent rebound hypertension.

11. Summary Table

Drug	Selectivity	Half-life	Major Use	Major Side Effect
Phentolamine	α1 + α2	20 min	Pheochromocytoma crisis	Reflex tachycardia
Phenoxybenzamine	α1 + α2 (irreversible)	24–72 h	Pheochromocytoma	Orthostatic hypotension
Prazosin	α1	3 h	HTN, PTSD	First-dose hypotension
Doxazosin	α1	22 h	HTN, BPH	Dizziness
Terazosin	α1	12 h	HTN, BPH	Syncope
Tamsulosin	α1A	9–15 h	BPH	Ejaculatory dysfunction

12. Summary

Alpha blockers provide therapeutic benefits in hypertension, BPH, and certain catecholamine excess states by blocking α1-adrenergic receptors, leading to vasodilation and smooth muscle relaxation.
While effective, they require careful dosing and monitoring due to risks of orthostatic hypotension, reflex tachycardia, and dizziness.
Their role in combination therapy remains valuable, particularly for BPH with coexistent hypertension.

13. References

Rang HP, Dale MM, Ritter JM, Flower RJ, Henderson G. Rang and Dale’s Pharmacology, 9th Ed., Elsevier, 2020.
Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 14th Ed., McGraw-Hill, 2021.
Chobanian AV, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7). JAMA. 2003.
Lepor H. Alpha-Blockers for the Treatment of Benign Prostatic Hyperplasia. Rev Urol. 2007;9(Suppl 1):S3–S14.
Raskind MA, et al. Prazosin for the Treatment of Nightmares Related to PTSD. Am J Psychiatry. 2007;164:188–193.