Diuretics have been used to treat
hypertension since 1958. The doses used were relatively high. Dose-dependent side effects and the increasing availability of other drugs such as beta- and alpha-blockers,
calcium-entry blockers, and
angiotensin-converting enzyme (
ACE) inhibitors, with equal
antihypertensive efficacy but additional effects in
cardiovascular diseases, led to a decrease in
diuretic use. In controlled trials, little or no protection against
coronary artery disease (CAD) was discussed as being due to the
diuretics' side effects. The main side effects are
hypokalemia,
hyperglycemia, and
hyperlipidemia.
Hypokalemia occurs most often (up to 30%) in
thiazide-treated hypertensive patients, and may cause arrhythmias in patients with CAD. This side effect is clearly dose-dependent and may be avoided by comedication with antikaliuretics.
Glucose intolerance may develop in about 3% of
diuretic-treated men and is reversible after discontinuation of the
diuretic. This side effect is functionally correlated with
hypokalemia and therefore is not seen when patients are given a comedication (for example,
spironolactone prevents
hypokalemia).
Hypercholesterolemia was first reported in 1964 during long-term
diuretic treatment. During the first 12 weeks of treatment,
low-density lipoprotein (
LDL) cholesterol increased 5-15% in men and postmenopausal women. After 1 year of
therapy, the levels decreased to pretreatment values. However, in placebo-controlled trials, the placebo groups exhibited
cholesterol levels falling below the
diuretic group. Although the mechanisms and the clinical implications of these side effects are not completely understood, the perception grew that
diuretics per se may have been at least partially responsible for the lack of protection against CAD.(ABSTRACT TRUNCATED AT 250 WORDS)