Effects of Disease

Few studies have assessed the pharmacokinetics and pharmacodynamics of thiazide diuretics in the clinical conditions in which they are used. In general, changes seem to be similar to those discussed with loop diuretics. No studies have assessed pharmacodynamics. Patients with decreased renal function have slowed elimination of tizolemide and trichlormethiazide with an inverse correlation of elimination half-life with creatinine clearance. This effect would presumably result in a diminished peak diuresis and a prolonged response compared to healthy subjects. No studies have assessed this hypothesis, probably because thiazides are relatively ineffective in patients with decreased renal function. One study showed no difference from normal in the time at which the peak concentration of chlorothiazide occurred in patients with cirrhosis.

The influence of CHF on the disposition of chlorothiazide, hydrochlorothiazide, and hydroflumethiazide has been assessed. As with loop diuretics, patients with concomitant decreases in renal function had longer half-lives of elimination. In contrast to loop diuretics, CHF does not delay absorption of the thiazides. Consequently, patients with CHF with relatively normal renal function do not differ from healthy subjects in the pharmacokinetics of thiazide diuretics.

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