The influence of indomethacin and sulindac on some pharmacological actions of atenolol in hypertensive patients.

Abstract

Indomethacin and sulindac were used as tools to study the role of renal and/or systemic prostaglandins in the pharmacological response to atenolol. Patients receiving chronic treatment with atenolol 100 mg received indomethacin 50 mg twice daily or sulindac 200 mg twice daily in a randomised crossover trial. Indomethacin significantly reduced the antihypertensive action of atenolol while sulindac had no effect. The role that systemic and/or renal prostaglandins may play in the antihypertensive action of atenolol is discussed with reference to renal PGI production and inhibition of platelet cyclo-oxygenase.

Nonsteroidal Anti-Inflammatory Drugs and Antihypertensives

“…The blunting of the anti hypertensive effect has not been, however, uniformly observed [15, 20-22, 24, 25]. While there are suggestions that the variability may be due to the class of NSAIDs [10,26,30], this is not a consistent finding. 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.…”

“…As both classes of drugs reduce PRA, pre-ß-blocker administration of NSAIDs may limit the antihy pertensive component related to PRA lowering. The blunting of the antihypertensive effect has not been ob served uniformly in all studies [24,29,30,32], The differ ences in some of the results between nonselective and selective beta blockers may be due to the fact that inhibi tion of prostaglandin synthesis might result in increased adrenoceptor sensitivity. Enhancement of alpha-medi ated vascular tone by NSAIDs might, therefore, be more apparent in the presence of a nonselective beta blocker than in the presence of a highly cardioselective one.…”

“…Increased circu lating prostaglandins may play a role in the antihyperten sive effects of ß-blockers [11,23,27,30,31], and suppres sion of their production by the use of NSAIDs will result in attenuation of this effect. This is suggested by several studies showing that the reduction in the urinary 6-keto-PGF, (the metabolite of the main vasodilatory prosta noid prostacyclin, PGI2 correlated with an increase in blood pressure [23,30,31]. The second factor may involve elimination of a potential hypotensive mechanism of ß-blockers.…”

Flurbiprofen interaction with single doses of atenolol and propranolol.

“…For example, the antihypertensive efficacy of propranolol (Durao et al, 1977;Watkins et al, 1980), oxprenolol (Salvetti et al, 1982a) and atenolol (Salvetti et al, 1982b) appear to be attenuated by indomethacin. In contrast, other NSAID such as sulindac (Salvetti et al, 1983), naproxen and aspirin (Chalmers et al, 1983) appear not to be implicated in such effects. The aim of this study was to investigate in hypertensive patients the interaction between flurbiprofen, a phenylalkanoic acid derivative, and two ,-adrenoceptor antagonists, propranolol and atenolol.…”

??-Blockers Drug Interactions of Clinical Significance

“…[89,90] In addition, when given with propranolol, heart rate reduction as well as efficacy in the treatment of premature ventricular contractions were reduced. [9I , 92) In animals, the mechanism for this effect might be a reduction in the number of ~-receptors found in the heart and presumably vascular smooth muscle.…”