CHLOROTHIAZIDE AND HYDROCHLOROTHIAZIDE: A COMPARATIVE STUDY OF THEIR HYPOTENSIVE, SALURETIC AND HYPERURICEMIC ACTION

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Abstract
Twenty-three patients with "chronic hypertensive cardiovascular disease" were studied. Daily doses of the drugs were 1000 mg and 500 mg chlorothiazide, and 100 and 50 mg of hydrochlorothiazide. The serum concentration and 24-hour urinary excretion of Na, K and uric acid were measured regularly. The effects of oral administration of the drug and the placebo on blood pressure and total body weight was also observed. For the analysis of the data the classical method of "two way analysis of variance" was used. To determine the significance of the "F" ratio thus obtained; and to make all pertinent comparisons between mean values, a further analysis was carried on according to the method described by Scheffe. Although there was a highly significant (P< 0.001) reduction in both systolic and diastolic blood pressure in all the patients, there was no significant difference between the 2 drugs, or the 2 different doses of each drug. Prolonged oral administration of both doses of chlorothiazide and hydrochlorothiazide caused a highly significant (P< 0.001) rise in the serum uric acid concentration. The average serum urea N remained within normal limits during the study. Despite normal serum urea N level in all patients, the average serum uric acid was elevated even before chlorothiazide or nydrochlorothiazide was administered. The significance of this observation as a possible indication of early renal deterioration in hypertension is currently under investigation. The differences in mean serum K concentration during the chlorothiazide, hydrochlorothiazide and placebo in the entire group of patients were highly significant (P < 0.001). The fall in serum K was greater with higher doses of each drug. Comparing the smaller dosage of each drug, the fall in serum K was greater with hydrochlorothiazide than with chlorothiazide. The changes in serum Na concentration were not significant and this was attributed to the fact that the patients retained normal Na balance by the time the serum Na was measured. The variations in 24-hour urine volume, and 24-hour urinary excretion of Na and K were not of the magnitude to affect the analysis of variance as a whole. Chlorothiazide and hydrochlorothiazide (each at 2 different dose levels) have the same effects on blood pressure, serum level of Na, K and uric acid. For all practical purposes the lower dosage is to be recommended since it has as much hypotensive effect as the higher dose and less kaluretic effect.