Presentation

It is presented as 10 mg phentolamine mesylate in 1 ml clear pale-yellow solution. The intravenous dose is 1–5 mg and should be titrated to effect. The onset of action is 1–2 minutes and its duration of action is 5–20 minutes.

Uses

Phentolamine is used in the treatment of hypertensive crises due to excessive sympathomimetics, monoamine oxidase inhibitor (MAOI) reactions with tyramine and phaeochromocytoma, especially during tumour manipulation. It has a role in the assessment of sympathetically mediated chronic pain and has previously been used to treat pulmonary hypertension. Injection into the corpus cavernosum has been used to treat impotence due to erectile failure.

Effects

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  Cardiovascular – α₁-blockade results in vasodilatation and hypotension while α₂-blockade facilitates noradrenaline release leading to tachycardia and a raised cardiac output. Pulmonary artery pressure is also reduced. Vasodilatation of vessels in the nasal mucosa leads to marked nasal congestion.

  
  
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  Respiratory – the presence of sulfites in phentolamine ampoules may lead to hypersensitivity reactions, which are manifest as acute bronchospasm in susceptible asthmatics.

  
  
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  Gut – phentolamine increases secretions and motility of the gastrointestinal (GI) tract.

  
  
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  Metabolic – it may precipitate hypoglycaemia secondary to increased insulin secretion.

Kinetics

The oral route is rarely used and has a bioavailability of 20%. It is 50% plasma protein-bound and extensively metabolised, leaving about 10% to be excreted unchanged in the urine. Its elimination half-life is 20 minutes.

Presentation

It is 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 pre-operative management of phaeochromocytoma (to allow expansion of the intravascular compartment), peri-operative management 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 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

Its effects 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

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  Cardiovascular – hypotension, which may be orthostatic, and reflex tachycardia are characteristic. Overdose should be treated with noradrenaline. Adrenaline will lead to unopposed β effects 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.

  
  
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  Central nervous system – it usually causes marked sedation although convulsions have been reported after rapid intravenous infusion. Miosis is also seen.

  
  
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  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 intravenous dose. The plasma half-life is about 24 hours and its effects may persist for 3 days while new α-adrenoceptors are synthesised. It is metabolised in the liver and excreted in urine and bile.

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

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  Cardiovascular – prazosin produces vasodilatation of arteries and veins and a reduction of systemic vascular resistance with little or no reflex tachycardia. Diastolic 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.

  
  
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  Urinary – it relaxes the bladder trigone and sphincter muscle thereby improving urine flow in those with benign prostatic hypertrophy. Impotence and priapism have been reported.

  
  
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  Central nervous system – fatigue, headache, vertigo and nausea all decrease with continued use.

  
  
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  Miscellaneous – it may produce a false-positive when screening urine for metabolites of noradrenaline (VMA and MHPG seen in phaeochromocytoma).

Kinetics

Plasma levels peak about 90 minutes following an oral dose with a variable oral bioavailability of 50–80%. It is highly protein-bound, mainly to albumin, and is extensively metabolised in the liver by demethylation and conjugation. Some of the metabolites are active. It has a plasma half-life of 3 hours. It may be used safely in patients with renal impairment as it is largely excreted in the bile.