The effects of nonsteroidal anti-inflammatory drugs on human hypertensive vascular disease.
The co-administration of nonsteroidal anti-inflammatory drugs (NSAIDs) and antihypertensive agents often, but not always, results in blunting of the effect of antihypertensive therapy. Although NSAIDs have no detectable pressor effects in normal subjects or untreated hypertensive people, they seem to antagonize the action of the majority of antihypertensive agents, making it necessary to increase their dosage, and often preventing proper control of blood pressure, particularly in black and elderly patients. The mechanism of this pharmacodynamic interaction is not completely understood, but may involve inhibition of vascular and renal prostaglandin (PG) synthesis, with resulting vasoconstriction and impaired renal excretion of Na+ and water. Also, suppression of a possible intermediary action of PG in the antihypertensive action of agents such as angiotensin converting enzyme inhibitors has been proposed. Certain antihypertensive drugs, such as Ca(2+)-channel blockers, centrally acting alpha agonists, and diuretics seem less sensitive to antagonism by NSAIDs. Aspirin and sulindac seem to be devoid of pressor effects, and thus provide a safe alternative in patients at risk for this interaction. These compounds may, in selected circumstances, even potentiate the effects of antihypertensive medications. Studies are underway to evaluate the hemodynamic effects of more selective blockers of arachidonate metabolism, such as thromboxane synthase inhibitors and selective inhibitors of PGH synthase-2.
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Department of Pharmacology, University of Chieti G. D'Annunzio School of Medicine, Italy.
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Patrono
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D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001241:Aspirin / Q000009:adverse effects; D001794:Blood Pressure / Q000187:drug effects*; D004347:Drug Interactions; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001241:Aspirin