Generic Name

Prazosin

Mechanism

Prazosin is a selective α1‑adrenergic receptor antagonist. By competitively blocking α1 receptors in vascular smooth muscle, it prevents norepinephrine‑induced vasoconstriction, leading to:
• Peripheral vasodilatation
• Decreased systemic vascular resistance
• Reduced preload (especially in the venous system)

Because it has minimal β‑blocker activity, it typically spares beta‑adrenergic tone, which is why it is preferred in patients who need pure α‑adrenergic blockade.

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Pharmacokinetics

• Absorption: Rapid; peak plasma concentrations in 1–2 h after oral dosing.
• Bioavailability: ~ 50 % (first‑pass hepatic metabolism).
• Distribution: Widely distributed; crosses the blood–brain barrier.
• Metabolism: Hepatic via CYP3A4 (major pathway).
• Elimination: Renal (≈ 50 %) and biliary excretion.
• Half‑life: 4–6 h; steady state in ~24 h with twice‑daily dosing.
• Drug interactions:
• CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) ↑ levels.
• Concomitant antihypertensives amplify hypotensive effect.

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Indications

• Primary treatment of hypertension—typically as once‑daily or twice‑daily dosing.
• Post‑traumatic stress disorder (PTSD) nightmares at low doses (0.125–0.25 mg twice daily).
• Benign prostatic hyperplasia (BPH) (off‑label): improvement of lower‑tract symptoms in men with moderate prostate enlargement.

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Contraindications

• Contraindications
• Severe orthostatic hypotension.
• Known hypersensitivity to aliskiren or other α1‑blockers.
• Warnings
• First‑dose “first‑hit” orthostatic hypotension: Recommend stepping up dose slowly.
• Pregnancy: Category C; use only if benefits outweigh risks.
• Renal impairment: Dose reduction recommended; monitor creatinine.
• Hepatic impairment: Generally safe; monitor liver enzymes.

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Dosing

Administration tips:
• Use a wijesh timer or alarm to avoid dosing the same blister in a 4‑hour gap.
• Gradually reduce dose upon discontinuation to avoid rebound hypertension.

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Adverse Effects

Common (≥ 5 %)
• Dizziness, orthostatic light‑headedness
• Headache
• Fatigue, weakness
• Retrograde ejaculation (in men)

Serious (≤ 1 %)
• Severe orthostatic hypotension → syncope, falls
• Severe bradycardia (rare)
• Hepatotoxicity (elevated ALT/AST) → check LFTs monthly for first 3 months
• Hypersensitivity rash, anaphylaxis

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Monitoring

• BP & HR: Every 2–4 weeks until stability, then at each visit.
• Orthostatic vitals after initial dose and on titration.
• Serum creatinine & eGFR at baseline and every 3 months.
• Liver function tests baseline; repeat at 3 and 6 months if clinically indicated.
• Pregnancy test in women of childbearing potential.

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Clinical Pearls

• First‑dose heart‑block: When initiating therapy in the elderly or those on β‑blockers, start at 0.125 mg once nightly and titrate upward to mitigate the “first‑hit” drop in blood pressure.
• Splitting the dose for PTSD: Low-dose, divided regimens maintain consistent peripheral α1 blockade and reduce rebound nightmares.
• Rapid absorption: Prazosin’s quick onset makes it a good first‑line agent when immediate BP reduction is needed (e.g., in a hypertensive emergency, a concurrent medication can act additively).
• Drug–drug interactions: Avoid co‑administration with potassium‑sparing diuretics or ACE inhibitors without careful BP monitoring, as the additive hypotensive effect may precipitate renal dysfunction.
• Intravenous transition: If a patient is switched from an IV vasodilator (e.g., nitroprusside) to oral prazosin, allow a 4‑hour wash‑out period to avoid sudden blood‑pressure collapse.
• Discontinuation alert: Abrupt cessation can cause rebound hypertension; taper over 2–3 days while monitoring BP.

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• References

1. Ganong’s *Review of Medical Physiology* – α1‑blocker mechanisms.

2. FDA labeling for Prazosin (Bayer).

3. Katzung & Trevor – *Basic & Clinical Pharmacology* (15th ed.) – pharmacokinetics & dosing.

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