Loop
diuretics and Thiazides
The use of
ACE inhibitors with loop or thiazide
diuretics is normally safe and effective, but `first-dose hypotension' (dizziness, fainting) can occur, particularly if the dose of diuretic is high (greater than
furosemide 80 mg daily or equivalent) and often in association with predisposing conditions (heart failure, renovascular hypertension, haemodialysis, high levels of renin and angiotensin, low-sodium diet, dehydration,
diarrhoea or vomiting, etc.). In addition,
renal impairment, and even acute
renal failure, have been reported, and diuretic-induced hypokalaemia may occur when
ACE inhibitors are used with potassium-depleting
diuretics.
First-dose hypotension is well established. For those with risk factors consider temporarily stopping the diuretic or reducing its dosage a few days before the ACE inhibitor is added, but if this is not clinically appropriate give the first dose of the ACE inhibitor under close supervision.
ACE inhibitors should be started with a very low dose, even in patients at low risk (e.g. those with uncomplicated essential hypertension taking low-dose thiazides). All patients should be given a simple warning about what can happen and what to do if hypotension occurs. The immediate problem (dizziness etc.) can usually be solved by the patient lying down. Any marked hypotension is normally transient, but if not it may be necessary to temporarily reduce the diuretic dosage. Severe reactions (e.g.
renal impairment or hypokalaemia) are rare, and routine monitoring during the initiation of the ACE inhibitor should suffice. However, if increases in urea and
creatinine occur, a dosage reduction and/or discontinuation of the diuretic and/or ACE inhibitor may be required.
Potassium-sparing
diuretics The use of
ACE inhibitors with
potassium-sparing diuretics, such as amiloride,
eplerenone,
spironolactone and
triamterene can result in hyperkalaemia, particularly in the presence of other risk factors (e.g. advanced age,
diabetes, doses of
spironolactone greater than 25 mg daily, and particularly
renal impairment).
The concurrent use of
ACE inhibitors and amiloride or
triamterene is normally not advised, but if both drugs are appropriate potassium levels should be closely monitored. The presence of a loop or thiazide diuretic may not necessarily prevent hyperkalaemia. The combination of an ACE inhibitor and
spironolactone or
eplerenone is beneficial in some indications, but close monitoring of
serum potassium and
renal function is needed, especially with any changes in treatment or in the patient's
clinical condition. It has been suggested that
spironolactone should not be given with
ACE inhibitors in those with a glomerular filtration rate of less than 30 mL/minute.