D. ALPHA RECEPTOR BLOCKING DRUGS
1. Prazosin: Prazosin is an a1-selective blocking drug. It is much more
useful for the treatment of hypertension than the less selective à-
blockers phentolamine and phenoxybenzamine because it evokes little if
any reflex tachycardia. Prazosin has also been used in the treatment of
congestive heart failure (see Chapter 4). Terazosin is a newer, somewhat
longer-acting a1-selective agent. Its therapeutic and adverse effects
are very similar to those of prazosin.
* Congestive heart failure (unlabeled).
* Raynaud's syndrome (unlabeled).
Contraindications, Adverse Reactions, and Overdose Toxicity:
* Severe postural hypotension after the first dose especially in
hypovolemic (eg, diuresed) patients. Syncope may result. The effect is
best managed by starting therapy with the minimum dose (1 mg) ad-
ministered just after going to bed. The effect usually diminishes rapid-
ly after the first dose and the dosage can then be incremented as re-
* Dizziness, headache, and sedation occur in 5-10% of patients at the
start of therapy, diminishing thereafter.
* Fluid retention often occurs in patients not also treated with a
* Overdose: Hypotension and CNS depression have been reported.
Interactions: The drug would be expected to have additive effects with
all other antihypertensive agents.
2. Phenoxybenzamine: Phenoxybenzamine is an irreversible à-receptor
blocker. It produces a powerful but nonselective sympathoplegia; com-
pensatory responses include tachycardia and fluid retention.
* Reduction of urinary bladder sphincter tone in urinary bladder dis-
orders (unlabeled). Contraindications and warnings:
* Orthostatic hypotension (warning), especially if it would result in
risk of stroke or myocardial ischemia (true of all hypotensive agents).
Adverse effects and Overdosage Toxicity:
* Excessive alpha sympathetic blockade: hypotension, nasal congestion,
miosis, and impairment of ejaculation.
* Nausea, vomiting, diarrhea.
3. Phentolamine: Phentolamine is a competitive alpha receptor blocking
drug. It is not selective for à1 or à2 receptors.
* Treatment of acute hypertensive reactions in patients with
pheochromocytoma. It is also approved for use as a provocative test for
pheochromocytoma, although this test is hazardous (because of the risk
of excessive hypotensive response) and has been superseded by measure-
ment of urinary or plasma catecholamines and their metabolites.
Phentolamine is also labeled for the treatment of tissue necrosis due to
extravasation of norepinephrine or dopamine.
* Management of hypertensive crises arising from excessive
sympathomimetic action as in MAO inhibitor drug reactions and rebound
hypertension following clonidine withdrawal (unlabeled).
Contraindications and warnings: Same as for phenoxybenzamine.
* Sympathoplegic adverse effects, similar to those listed for
phenoxybenzamine but shorter in duration (15 min to 2 hr as compared to
24 to 48 hr for phenoxybenzamine).
* Gastrointestinal stimulation with increased acid secretion, nausea,
vomiting, and diarrhea.
* Overdose is characterized by transient hypotension that can usually be
managed by administration of fluids.