The effects of sulindac and indomethacin on the anti‐hypertensive and diuretic action of hydrochlorothiazide in patients with mild to moderate essential hypertension.

Abstract

1 In this double-blind two period crossover study, we investigated the effect of indomethacin and sulindac on blood pressure in 25 hypertensive patients being treated with hydrochlorothiazide. The study consisted of seven 4 week periods. In the first and the last period the patients took placebos, in period two, four and six they were treated with hydrochlorothiazide 50 mg once daily alone, and in the third and fifth period hydrochlorothiazide 50 mg once daily was given in combination with either indomethacin 50 mg twice daily or sulindac 200 mg twice daily in double-blind random order. 2 Blood pressure, measured by sphygmomanometer and arteriosonde, and body weight were determined every 2 weeks. Compared with placebo hydrochlorothiazide decreased the mean arterial pressure by 8%. Addition of both indomethacin and sulindac resulted in only slight and generally similar changes of this blood pressure lowering effect. This was found both for the whole group and when both treatment sequence groups were analysed separately. 3 In contrast to sulindac, indomethacin attenuated the hydrochlorothiazide-induced decreases of body weight, plasma potassium and the increase of plasma renin activity. Both non-steroidal anti-inflammatory drugs (NSAID) reduced the 24 h urinary excretion of prostaglandins (PGs), i.e. PGF2., 6 ketoPGF1, and thromboxane B2 except PGE2.4 From this study it can be concluded that, in contrast to sulindac, indomethacin attentuated the diuretic action of hydrochlorothiazide, hower apparently without consequences for its long-term blood pressure lowering effect. This study does not support the hypothesis that the difference between the two NSAIDs can be explained by different effects on renal PG synthesis.

Nonsteroidal Anti-Inflammatory Drugs and Antihypertensives

“…Sulindac has been observed to enhance the antihypertensive effect of di uretics in some studies [10,26], an effect related to its exclusively extrarenal prostaglandin inhibition. Other studies, however, have found sulindac to decrease renal thiazide clearance [21] and to have no effect on blood pressure in diuretic-treated patients [20,21]. Similar con troversial findings have been observed with indomethacin [20,21] and ibuprofen [10,22].…”

“…Hyporeninemic hypoaldosteronism has been demon strated in several studies in which NSAIDs were added to diuretics [10,18,20,21,28]. This development explains the increase in plasma potassium observed with the used NSAIDs.…”

“…The coadministration of NSAIDs and thiazides re sults in attenuation of the antihypertensive effect of the diuretics with an associated increase in body weight [10,[20][21][22][23][24] and plasma potassium levels [10,20,21], The atten uation of the antihypertensive effect likely results from blunting of the natriuresis of thiazides. Unlike the find ings with loop diuretics, however, there are no significant effects of indomethacin (used as a prototype of NSAIDs) on thiazide pharmacokinetics.…”

“…The use of indomethacin [15,20,21,25], diflunisal [15], sulindac [21], and ibuprofen [22] has led to suppression of the plasma renin activity (PRA). Diver gent findings, however, have been observed [10,22,24], The reasons for these disparate findings may be sought in the variable levels of endogenous renin secretion with different dietary Na intake [20], the méthodologie details of the studies at variance, and the dissimilar inhibitory potencies of the different classes of NSAIDs on renal prostaglandin synthesis [20,21,22,26]. On the other hand, some NSAIDs (sulindac) may not suppress PRA because they do not inhibit PGD synthesis (renal prostaglandins) which is a known stimulant of renin secretion [10,20,22].…”

Tedavi̇ Altindaki̇ Hi̇pertansi̇f Hastalarda Nonsteroidal Anti̇i̇nflamatuar İlaçlarin Anti̇hi̇pertansi̇f İlaçlarla Etki̇leşmeleri̇

“…Derg. 26 (2) Bununla beraber damar duvarlarında PGI 2 sentezini stimüle ettiği ve direkt antihipertansif etkisinin PGI 2 ile alakalı olduğu iddia edilmektedir (28,34,35,36 …”