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Section IIICardiovascular drugsTable 13.1.Actions of specificα-adrenoceptor stimulation.Receptor type Action
Post-synaptic
α 1 -Receptors vasoconstriction
mydriasis
contraction of bladder sphincter
α 2 -Receptors platelet aggregation
hyperpolarization of some CNS neurones
Presynaptic
α 2 -Receptors inhibit noradrenaline releasecardiac output. Pulmonary artery pressure is also reduced. Vasodilatation of vessels
in the nasal mucosa leads to marked nasal congestion.
Respiratory – the presence of sulphites in phentolamine ampoules may lead to
hypersensitivity reactions, which are manifest as acute bronchospasm in suscep-
tible asthmatics.
Gut–phentolamine increases secretions and motility of the gastrointestinal tract.
Metabolic – it may precipitate hypoglycaemia secondary to increased insulin secre-
tion.Kinetics
The oral route is rarely used and has a bioavailability of 20%. It is 50% plasma protein
bound and extensively metabolized, leaving about 10% to be excreted unchanged in
the urine. Its elimination half-life is 20 minutes.Phenoxybenzamine
Phenoxybenzamine is a long-acting non-selectiveα-blocker. It has a high affinity for
α 1 -adrenoceptors.Presentation
Itis presented as capsules containing 10 mg and as a clear, faintly straw-coloured
solution for injection containing 100 mg/2 ml phenoxybenzamine hydrochloride
with ethyl alcohol, hydrochloric acid and propylene glycol.Uses
Phenoxybenzamine is used in the preoperative management of phaeochromocy-
toma (to allow expansion of the intravascular compartment), peri-operative man-
agement of some neonates undergoing cardiac surgery, hypertensive crises and
occasionally as an adjunct to the treatment of severe shock. The oral dose starts
at 10 mg and is increased daily until hypertension is controlled, the usual dose is 1–2
mg.kg−^1 .day−^1 .Intravenous administration should be via a central cannula and the