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9780521704632c15 CUFX213A/Peck 9780521618168 December 28, 2007 13:25
15 Vasodilatorswhich may be repeated after 15 minutes. It has also been used to treat intractable
hypoglycaemia and malignant islet-cell tumours.Mechanism of action
Itshypotensive effects are mediated through altered levels of cAMP in arterioles,
producing vasodilation. It may also be due to a reduced Ca^2 +influx. Its biochemi-
cal effects are due to inhibition of insulin secretion and increased release of cate-
cholamines.Effects
Cardiovascular – diazoxide produces arteriolar vasodilation with little effect on
capacitance vessels. As a result the blood pressure falls and there is an increase in
heart rate and cardiac output. Postural hypotension is not a problem.
Metabolic – it increases the levels of glucose, catecholamines, renin and aldos-
terone. It also causes fluid retention (despite its chemical relation to the thiazides),
which may require treatment with a loop diuretic.
Miscellaneous – the following effects may occur: nausea, especially at the
start of treatment, extra-pyramidal effects including occulogyric crisis, thrombo-
cytopenia and hyperuricaemia.Kinetics
Diazoxide is well absorbed from the gut with an oral bioavailability of 80%, and is
extensively protein-bound in the plasma (about 90%). The hyperglycaemic effects
last about 8 hours while the hypotensive effects last about 5 hours. The plasma half-
life, however, may last up to 36 hours. It is partly metabolized in the liver, being
excreted in the urine as unchanged drug and as inactive metabolites.