Pharmacology for Anaesthesia and Intensive Care

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13 Adrenoceptor antagonists

usual dose is 1 mg.kg−^1 .day−^1 given as a slow infusion in at least 200 ml 0.9% saline.

β-blockade may be required to limit reflex tachycardia.

Mechanism of action

Itseffects are mediated by a reactive intermediate that forms a covalent bond to the

α-adrenoceptor resulting in irreversible blockade. In addition to receptor blockade,

phenoxybenzamine inhibits neuronal and extra-neuronal uptake of catecholamines.

Effects


Cardiovascular – hypotension, which may be orthostatic, and reflex tachycardia are

characteristic. Overdose should be treated with noradrenaline. Adrenaline will lead

to unopposedβeffects thereby compounding the hypotension and tachycardia.

There is an increase in cardiac output and blood flow to skin, viscera and nasal

mucosa leading to nasal congestion.


Central nervous system – it usually causes marked sedation although convulsions

have been reported after rapid intravenous infusion. Meiosis is also seen.


Miscellaneous – impotence, contact dermatitis.

Kinetics

Phenoxybenzamine is incompletely and variably absorbed from the gut (oral

bioavailability about 25%). Its maximum effect is seen at 1 hour following an intra-

venous dose. The plasma half-life is about 24 hours and its effects may persist for 3

days while newα-adrenoceptors are synthesized. It is metabolized in the liver and

excreted in urine and bile.

Selectiveα 1 -blockade

Prazosin

Prazosin (a quinazoline derivative) is a highly selectiveα 1 -adrenoceptor antagonist.

Presentation and uses

Prazosin is available as 0.5–2 mg tablets. It is used in the treatment of essential

hypertension, congestive heart failure, Raynaud’s syndrome and benign prostatic

hypertrophy. The initial dose is 0.5 mg tds, which may be increased to 20 mg per day.

Effects


Cardiovascular – prazosin produces vasodilatation of arteries and veins and a

reduction of systemic vascular resistance with little or no reflex tachycardia. Dias-

tolic pressures fall the most. Severe postural hypotension and syncope may follow

the first dose. Cardiac output may increase in those with heart failure secondary

to reduced filling pressures.