Prazosin

Prazosin is a short acting selective alpha 1 adrenergic antagonist. It lowers blood pressure by vasodilation and improves urinary flow in prostatic hyperplasia. Its hallmark hazard is first dose syncope. It is also used off label for nightmares in post-traumatic stress disorder and for Raynaud phenomenon.

Classification. Selective post synaptic alpha 1 blocker; quinazoline.

Mechanism. Blocks alpha 1 receptors on arteries, veins and the prostatic smooth muscle, lowering peripheral resistance and bladder neck tone, with little change in cardiac output.

Pharmacodynamics. Onset 2 hours, peak 2 to 4 hours, duration 7 to 10 hours after the early doses. Reflex tachycardia is small. Orthostatic hypotension is worst after the first dose.

Pharmacokinetics. Oral bioavailability about 60%; highly protein bound; extensive hepatic metabolism; half life 2 to 3 hours; excreted in bile and faeces.

Hypertension, adult (add on, not first line).

• First dose 0.5 mg at bedtime; continue 0.5 mg two or three times daily for 3 to 7 days.

• Increase to 1 mg two or three times daily, then titrate over weeks.

• Usual maintenance 3 to 15 mg daily in two or three divided doses; maximum 20 mg daily.

• Reduce other antihypertensives (especially diuretics) when starting.

Benign prostatic hyperplasia, adult (not first line). 0.5 mg twice daily for 3 to 7 days, then 2 mg twice daily; maximum 4 mg twice daily. Longer acting alpha blockers are preferred.

Raynaud phenomenon, adult (off label). 0.5 mg twice daily, increased to 1 to 2 mg twice daily if tolerated.

Nightmares in post-traumatic stress disorder, adult (off label, specialist). Start 1 mg at bedtime; increase by 1 to 2 mg every few days to a usual range of 3 to 15 mg at night; benefit varies.

Children, hypertension. 0.05 to 0.1 mg/kg daily in 2 or 3 divided doses; maximum 0.5 mg/kg daily or 20 mg daily. Specialist.

Restarting. If treatment lapses for more than a few days, restart at 0.5 mg.

Contraindications. Hypersensitivity to quinazolines; heart failure from mechanical obstruction (aortic stenosis, pericardial constriction); history of micturition syncope.

Warnings. First dose syncope 30 to 90 minutes after the first dose or a dose increase; give at bedtime and warn the patient to rise slowly. Orthostatic hypotension. Intraoperative floppy iris syndrome during cataract surgery. Priapism, rarely. Fluid retention with long use.

Adverse effects. Dizziness, headache, drowsiness, palpitations, nasal congestion, dry mouth, oedema, weakness, urinary incontinence.

Interactions. Sildenafil, tadalafil and other phosphodiesterase 5 inhibitors: symptomatic hypotension; start the inhibitor at the lowest dose and separate by 4 hours. Other antihypertensives, diuretics and beta blockers add hypotension. Verapamil and diltiazem raise levels modestly.

Special groups.

• Pregnancy: limited data; used when other drugs are unsuitable.

• Breastfeeding: small amounts in milk; acceptable with infant observation.

• Older adults: start with 0.5 mg at bedtime; falls risk.

• Kidney impairment: no adjustment; start with 0.5 mg and titrate.

• Liver impairment: reduce dose and monitor.

Formulations. Tablets and capsules 0.5 mg, 1 mg, 2 mg and 5 mg.

Administration. Oral, with or without food, with the first dose taken lying down at bedtime. Dose increases are also best taken at bedtime.

Baseline. Sitting and standing blood pressure, heart rate, prostate assessment, eye history of cataract surgery.

Monitoring. Pressure sitting and standing 2 to 4 hours after the first dose and after each dose increase; heart rate; symptoms of orthostasis; fluid status.

Stopping. Taper where possible; abrupt stopping does not cause rebound hypertension but pressure may rise again.

Common prescribing errors. Starting at 1 mg or more in a patient already on a diuretic; giving the first dose in the morning; forgetting to tell the eye surgeon.