Pharmacology for Anaesthesia and Intensive Care

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16 Antihypertensives

unchanged in the bile. It has a half-life of many days. It crosses the placenta and

BBB and also reaches breast milk.

Metirosine

Metirosine is a competitive inhibitor of tyrosine hydroxylase and can therefore pre-

vent the synthesis of catecholamines. It should only be used to manage hypertension

associated with phaeochromocytoma.

Itmay cause severe diarrhoea, sedation, extrapyramidal effects and hypersensi-

tivity reactions.

Centrally acting

Methyldopa

Presentation and uses

Methyldopa is available as film-coated tablets containing 125–500 mg and as an

oral suspension containing 50 mg.ml–1.The rarely used intravenous preparation is

colourless and contains 50 mg.ml–1and uses sodium metabisulphite as the preser-

vative. It is used at 250 mg tds increasing to a maximum of 3 g.day–1to control

hypertension, especially that associated with pregnancy.

Mechanism of action

Methyldopa readily crosses the BBB where it is decarboxylated toα-methyl-

noradrenaline, which is a potentα 2 -agonist. It retains limitedα 1 -agonist proper-

ties (α 2 :α 1 ratio 10:1). Stimulation of presynapticα 2 -receptors in the nucleus tractus

solitarii forms a negative feedback loop for further noradrenaline release so that

α-methyl-noradrenaline reduces centrally mediated sympathetic tone, leading to a

reduction in blood pressure.

Effects


Cardiovascular – its main effect is a reduction in systemic vascular resistance lead-

ing to a fall in blood pressure. Postural hypotension is occasionally a problem.

Cardiac output is unchanged despite a relative bradycardia. Rebound hyperten-

sion may occur if treatment is stopped suddenly but this is less common than with

clonidine.


Central nervous system – sedation is common, while dizziness, depression, night-

mares and nausea are less common. The MAC of volatile anaesthetics is reduced.


Haematological–apositive direct Coombs’ test is seen in 10–20% of patients taking

methyldopa. Thrombocytopenia and leucopenia occur rarely.


Allergic – it may precipitate an auto-immune haemolytic anaemia. Eosinophilia

associated with fever sometimes occurs within the first few weeks of therapy. A

hypersensitivity reaction may cause myocarditis.