NSAIDs, antihypertensive agents and loss of blood pressure control

American Family Physician,  March, 1995  by Lori L. MacFarlane,  Deborah J. Orak,  William M. Simpson

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CENTRAL [ALPHA.sub.2] AGONISTS

Central [alpha.sub.2] agonists stimulate [alpha.sub.2] receptors and inhibit efferent sympathetic activity in the peripheral vasculature.[12] Studies of the interaction between NSAIDS and central [alpha.sub.2] agonists are limited and mainly involve the effects of a single dose of an antihypertensive agent in the animal model. NSAIDs may antagonize the action of central [alpha.sub.2] agonists by increasing total peripheral resistance.[18]

PERIPHERAL ALPHA, BLOCKERS

Peripheral alpha, blockers act at the postsynaptic [alpha.sub.1] receptor, leading to both arteriolar and venous dilation.[12] Prostaglandins can alter vascular responses to sympathetic nerve stimulation, and prazosin (Minipress) has been shown to enhance the synthesis of [PG.sub.2] and [PGE.sub.2].[24] Through prostaglandin inhibition, NSAIDs increase vascular resistance and may attenuate the vasodilatory effect of peripheral alpha, blockers. Clinical trials reporting the interaction between NSAIDs and peripheral [alpha.sub.1] blockers in hypertensive subjects are lacking.[18] However, in an eight-hour study, indomethacin was found to blunt the hypotensive action of prazosin in normotensive subjects.[27]

CALCIUM CHANNEL BLOCKERS

Calcium channel blockers produce smooth muscle relaxation by blocking the inward movement of calcium ions in vascular smooth muscle. This action decreases the force of contraction of vascular smooth muscle and produces vasodilation. Calcium channel blockers induce natriuresis and diuresis, which may contribute to their hypotensive activity.[28-30] Clinical trials have evaluated the effects of sulindac and diclofenac (Cataflam, Voltaren) in elderly hypertensive patients treated with nifedipine (Adalat, Procardia)[31] (Table 2). The addition of either of these NSAIDs did not affect blood pressure. In healthy volunteers, indomethacin did not affect the antihypertensive efficacy of felodipine (Plendil).[32] Similar studies failed to find blood pressure changes with diltiazem Cardizem).[18]

Clinical Significance and Recommendations

Extrapolation of results from reported studies to all primary care patients is difficult because of the variations in blood pressure parameters measured and the populations studied. Although the problem of interaction between NSAIDs and antihypertensive medication may not occur in everyone, it should be considered when patients are receiving both medications, and therapy should be adjusted accordingly if blood pressure control becomes difficult.

Additional trials are necessary to determine the long-term effects of NSAIDs and antihypertensive agents on blood pressure control. Until then, the following recommendations should be considered: (1) blood pressure should be monitored frequently when NSAIDs are combined with diuretics, beta blockers or ACE inhibitors; (2) it appears that NSAIDs may be used with calcium channel blockers without an effect on blood pressure control; (3) indomethacin, the most potent prostaglandin inhibitor, appears to alter blood pressure control to a greater extent than weaker agents, such as sulindac. Although this supposition may be related to the fact that indomethacin has been studied more than the other NSAIDs, caution should still be exercised when combining indomethacin and antihypertensive agents; (4) NSAID use and its necessity should be evaluated before initiating therapy with an antihypertensive agent, before increasing the dosage of an antihypertensive agent and before adding an additional antihypertensive drug, and (5) if patients have lost blood pressure control while taking an NSAID/antihypertensive combination, acetaminophen or nonacetylated salicylates (choline-magnesium salicylate [Trilisate], salsalate [Amigesic, Disalcid, Salsitab]) may be considered as alternative therapy. These agents do not alter prostaglandin synthesis and, therefore, should not attenuate antihypertensive efficacy.