Makindo Medical Notes

Related Subjects: | Hypertension | Benign Prostatic Hyperplasia

About

• Doxazosin is an alpha-1 adrenergic receptor blocker used in the management of hypertension and benign prostatic hyperplasia (BPH).
• It relaxes vascular smooth muscle (↓ peripheral resistance) and relaxes bladder neck/prostatic smooth muscle (improves urinary flow).
• Not first-line for hypertension — used in combination or for resistant cases (NICE CG127).

Mode of Action 🧬

• Selective blockade of alpha-1 adrenergic receptors in arterioles and venules → vasodilation → ↓ systemic vascular resistance → ↓ blood pressure.
• In prostate/bladder: relaxation of smooth muscle → improves urinary flow in BPH.
• Does not affect alpha-2 receptors → less reflex tachycardia than non-selective alpha-blockers.

Indications 📋

• Hypertension: Second/third-line agent, particularly in resistant hypertension (added after ACEi/ARB, CCB, thiazide).
• Benign prostatic hyperplasia (BPH): Improves lower urinary tract symptoms (hesitancy, weak stream, nocturia).
• Phaeochromocytoma (rare): Sometimes used as adjunct alpha-blockade pre-surgery (though phenoxybenzamine more common).

Dose 💊

• Start: 1 mg once daily, titrate after 1–2 weeks.
• Usual: 4 mg once daily (can increase up to 16 mg/day).
• Modified-release formulations often preferred for convenience and reduced “first-dose” hypotension.

Pharmacokinetics

• Oral bioavailability ~65%.
• Half-life ~22 hours → allows once-daily dosing.
• Hepatic metabolism (CYP3A4), biliary and faecal excretion.

Interactions ⚠️

• Other antihypertensives: Additive hypotension (ACEi, diuretics, nitrates).
• PDE5 inhibitors (sildenafil, tadalafil): Risk of profound postural hypotension → separate dosing by several hours.
• NSAIDs: May blunt antihypertensive effect.

Contraindications 🚫

• Symptomatic hypotension.
• History of postural hypotension/syncope.
• Relative C/I in pregnancy and avoid in lactation (limited data).

Side Effects 🩺

• Vasodilatory: Dizziness, postural hypotension (especially after first dose — “first-dose effect”), headache, flushing.
• Cardiac: Palpitations, reflex tachycardia, oedema.
• General: Fatigue, weakness, flu-like symptoms.
• GI/liver: Rare cholestasis, hepatitis.
• Respiratory: Breathlessness, cough.

Clinical Pearls ✨

• 💡 First-dose effect: Marked postural hypotension/syncope can occur → start at night, especially in elderly.
• ⚡ Resistant hypertension: Often used after standard triple therapy (ACEi/ARB + CCB + thiazide).
• 👴 BPH: Relieves LUTS; compare with tamsulosin (more selective, less BP effect).
• ❤️ Cardiovascular risk: ALLHAT trial showed alpha-blockers inferior to thiazides for CV outcomes — explains why not first-line in HTN.

References

• BNF – Doxazosin
• NICE Hypertension in Adults (CG127)
• ALLHAT Collaborative Research Group. (2002). Major outcomes in high-risk hypertensive patients randomized to doxazosin vs chlorthalidone. JAMA.