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16 Antihypertensivesis forfeit. Therefore renal perfusion pressure falls and renal failure may follow. As
aresult bilateral renal artery stenosis or unilateral renal artery stenosis to a single
functioning kidney is considered a contraindication. Where normal renal perfu-
sion is preserved, renal vasodilatation may occur leading to a naturesis.
Metabolic – reduced aldosterone release impairs the negative feedback to renin
production so that renin levels become elevated. It may also lead to hyperkalaemia
and raised urea and creatinine, especially in those with even mildly impaired renal
function.
Interactions – captopril reduces aldosterone release, which may result in hyper-
kalaemia, so it should not be used with potassium-sparing diuretics. It has been
associated with unexplained hypoglycaemia in Type I and II diabetes. These effects
usually decrease with continued treatment. Non-steroidal anti-inflammatory
drugs reduce captopril’s antihypertensive effects and may precipitate renal fail-
ure.
Cough – a persistent dry cough may be the result of increased levels of bradykinin,
which are normally broken down by ACE. Non-steroidal anti-inflammatory drugs
may alleviate this cough but at the expense of reduced antihypertensive effects.
Miscellaneous – rare but serious effects may complicate its use and include angio-
oedema (0.2%, more common in black patients), agranulocytosis and thrombocy-
topenia. Less serious side effects are more common and include loss of taste, rash,
pruritus, fever and apthous ulceration. These are more common with higher doses
and in patients with impaired renal function.Kinetics
Captopril is well absorbed from the gut and has an oral bioavailability of 65%. It is
25% plasma protein bound. Approximately 50% is oxidized in the liver to the dimer
and mixed sulphides all of which are eventually excreted in the urine. It has an
elimination half-life of 4 hours, although this will be increased in the presence of
renal impairment.Enalopril
Kinetics
Enalopril is a prodrug, which is hydrolyzed in the liver and kidney to the active com-
pound enaloprilat. It may be given orally (as enalopril) or intravenously (as enalo-
prilat). Its elimination half-life is 4–8 hours but increases to 11 hours in prolonged
thereapy. It has a duration of action of approximately 20 hours.Angiotensin II receptor antagonists (ARAs)
Losartan
Losartan is a substituted imidazole compound.