Alpha Receptor Antagonists

Non-selective (α1 + α2): phenoxybenzamine (irreversible) and phentolamine (reversible) — used in phaeochromocytoma.

Selective α1 (non-subtype-selective): prazosin (short-acting), terazosin, doxazosin (long-acting), alfuzosin (functionally uroselective).

α1A-subtype selective (“uroselective”): tamsulosin, silodosin; naftopidil is relatively α1D-selective.

Selective α2 antagonists: yohimbine, idazoxan — of historical/limited use.

The bladder neck, prostatic stroma and prostatic urethra are rich in α1A receptors; blockade relaxes smooth muscle, lowers tonic luminal pressure in the prostatic fossa and improves urine outflow.

Vascular smooth muscle carries α1B receptors; blocking these causes vasodilatation, postural hypotension and reflex tachycardia — the basis of most adverse effects.

α1D receptors in the bladder body and spinal cord may mediate storage symptoms such as urgency and nocturia.

Uroselective agents (tamsulosin, silodosin) act preferentially on α1A and therefore cause less hypotension, broadening the population of elderly men who can be treated safely.

Lower urinary tract symptoms due to BPH — the principal use, and an excellent first-line option for men with bothersome symptoms who want treatment. Alfuzosin, doxazosin, tamsulosin, terazosin and silodosin are all appropriate.

Alpha blockers give rapid symptom relief within days, but do not alter the natural history of the disease and do not prevent long-term bladder outflow obstruction.

Combination with a 5α-reductase inhibitor is appropriate when the prostate exceeds about 40 mL. In the MTOPS study, combination therapy reduced acute urinary retention by 66%, versus 39% for alpha blockade alone and 34% for finasteride alone.

After 6–9 months of successful combination therapy the alpha blocker may be withdrawn, restarting it if symptoms recur.

Other uses: phaeochromocytoma (phenoxybenzamine pre-operatively), resistant hypertension (as add-on only), medical expulsive therapy for distal ureteric stones, prazosin for PTSD-related nightmares, and scorpion envenomation (prazosin) — relevant in Indian practice.

Alpha blockers have not been shown to reduce symptoms of chronic prostatitis/chronic pelvic pain syndrome, and increased dizziness and postural hypotension in trials.

First-dose and postural hypotension, dizziness, syncope, asthenia, headache and rhinitis occur in about 5–9%; these led to falls, fractures and institutionalisation in older men in observational studies.

Early agents were designed as antihypertensives, so orthostasis was a significant problem; normotensive men also complained of asthenia and fatigue. Dose titration at bedtime reduces this.

Intraoperative floppy iris syndrome (IFIS) — iris billowing, prolapse and progressive miosis during cataract surgery. Tamsulosin carries by far the highest risk; stopping the drug does not reliably prevent it, so the ophthalmologist must be informed before surgery.

Retrograde or absent ejaculation is common, especially with silodosin and tamsulosin — a frequently under-discussed quality-of-life issue.

Interactions: additive hypotension with PDE5 inhibitors, nitrates, diuretics and other antihypertensives; caution in patients with autonomic failure or Parkinson’s disease.

Beers criteria advise against using peripheral α1 blockers as routine antihypertensives in older adults because of orthostatic hypotension; in ALLHAT the doxazosin arm was terminated early for excess heart failure.