Nonsteroidal anti-inflammatory drugs and antihypertensives

Approximately 60 million people in the United States have hypertension (BP greater than or equal to 140/90 mm Hg), 40 million have arthritis clinically suitable for nonsteroidal anti-inflammatory drug (NSAID) therapy, and millions take NSAIDs for nonarthritic conditions, creating considerable potential for concomitant administration of NSAIDs and antihypertensive agents. It is estimated that more than 20 million people are on concurrent therapy. Most NSAIDs produce mild elevations of normal blood pressure levels and can partially or completely antagonize the effects of many antihypertensive drugs. The effect on blood pressure can vary from no effect to hypertensive crisis. In pooled studies, the average increase in mean arterial pressure was 10 mm Hg, and duration was short-lived or chronic. Significant interactions occur in about 1% of patients per year. The risk is greatest in the elderly, blacks, and patients with low-renin hypertension. NSAIDs may block the antihypertensive effects of thiazide and loop diuretics, beta-adrenergic blockers, alpha-adrenergic blockers, and angiotensin-converting enzyme inhibitors. No interactions have been reported with centrally acting alpha agonists or the calcium channel blockers. The mechanism of the hypertensive effects of NSAIDs seem primarily related to their ability to block the cyclo-oxygenase pathway of arachidonic acid metabolism, with a resultant decrease in prostaglandin formation. The prostaglandins are important in normal modulation of renal and systemic vascular dilatation, glomerular filtration, tubular secretion of salt and water, adrenergic neurotransmission, and the renin-angiotensin-aldosterone system. Blockade of salutary effects of prostaglandins by NSAIDs results in a complex series of events culminating in attenuation of the effects of many antihypertensive agents. High-risk patients treated with NSAIDs should be identified and have blood pressure, renal function, and serum potassium frequently monitored.