Hypertension ibuprofen effect

Selectivity for COX-1 versus COX-2 is variable and incomplete for the older NSAIDs, but many selective COX-2 inhibitors have been synthesized. The selective COX-2 inhibitors do not affect platelet function at their usual doses. In testing using human whole blood, aspirin, ibuprofen, indomethacin, piroxicam, and sulindac are somewhat more effective in inhibiting COX-1. The efficacy of -2-selective drugs equals that of the older NSAIDs, while gastrointestinal safety may be improved. On the other hand, selective COX-2 inhibitors may increase the incidence of edema and hypertension. As of December 2008, celecoxib and the less selective meloxicam are the only COX-2 inhibitors marketed in the USA. Rofecoxib and valdecoxib, two previously marketed, selective COX-2 inhibitors, have been withdrawn from the market due to their association with increased cardiovascular thrombotic events. Celecoxib has an FDA-initiated "black box" warning concerning cardiovascular risks. It has been recommended that all NSAID product labels be revised to include cardiovascular risks. 

Non-steroidal anti-inflammatory drugs (NSAIDs) are often reported to interfere with the blood pressurelowering action of thiazide diuretics (SED-14, 667). In 17 women with arthritis and hypertension taking fosinopril and hydrochlorothiazide, ibuprofen, sulindac, and nabu-metone, each for 1 month, had no effect on mean arterial pressure (47). These results suggest that the ACE inhibitor fosinopril may neutralize the tendency of NSAIDs to increase blood pressure in thiazide-treated hypertensive patients. However, the design of this study precluded such a conclusion, since no evidence was provided that any of the NSAIDs increased blood pressure in the absence of fosinopril. Furthermore, the numbers were small and the precision of the comparison is likely to have been low. Careful monitoring of blood pressure is necessary when NSAIDs are introduced in thiazide-treated hypertensive patients, even when ACE inhibitors are co-prescribed. 

Two studies that compared the interaction of celecoxib with ACE inhibitors found no difference in blood pressure effects compared to placebo [58, 59]. In one study (n=359), the blood pressure (systohc and diastolic) effects of celecoxib 200 mg BID and nabumetone 1 g BID were found to be similar to placebo, but significantly different from ibuprofen 800 mg IID [58]. In the second study (n=178), the effects of celecoxib 400 mg daily and placebo on 24-hour blood pressure in hypertensive patients controlled on hsinopiil 10-40 mg daily was evaluated [59]. No difference between groups was observed in 24-hour ambulatory SBP. The difference between groups in 24-hour diastolic BP was only 1.4 mm Hg. The change from baseline in 24-hour blood pressure (1.8 mm Hg/1.4mm Hg) is less than what has been the effect of NSAIDs on the SBP (defined as an increase >20 mm Hg with an absolute value of >140 mm Hg) reported for traditional NSAIDs in ACE inhibitor-treated patients. On the other hand, co-ad-ministration of rofecoxib 25 mg daily with benazepril 10-40 mg for 4 weeks in patients with mild to moderate... 

Palmer RFI, Flaig AE, Flavin SK, Lyengaer NK. Effects of Ibuprofen, nabumetone and celecoxib on blood pressure control in hypertensive patients on ACE inhibitors. American Journal of Flypertension 2001 4 85A. 

Alam S, Purdle DM, Johnson AG, Alam S, Purdie DM, Johnson AG. Evaluation ofthe potential interaction between NaCI and prostaglandin inhibition in elderly individuals with isolated systolic hypertension. Journal of Hypertension 1999 7 1195-1202. Brater DC, Anderson S, Baird Betal. Effects of ibuprofen, naproxen, and sulindacon prostaglandins in men. Kidney International 1985 27 66-73. 

In the recent 8000-patient celecoxib long-term arthritis safety study [123], significantly more patients receiving traditional NSAlDs (ibuprofen or diclofenac) experienced clinically significant elevations in serum creatinine and/or serum urea nitrogen levels when compared to celecoxib. In an equally large gastrointestinal safety trial with rofecoxib, the incidence of adverse effects related to renal function for rofecoxib was similar to naproxen (1.2% versus 0.9%, respectively) [124]. When rofecoxib and celecoxib were directly evaluated in elderly hypertensive OA patients who manifested "normal" serum creatinine at the time of study recruitment, the overall incidence of clinically... 

In one study, sulindac 200 mg twice daily given to patients taking capto-pril 100 to 200 mg twice daily caused only a small rise in blood pressure (from 132/92 to 137/95 mmHg). Sulindac 150 mg twice daily did not attenuate the blood pressure response to captopril when it was substituted for ibuprofen in an elderly woman. Similarly, sulindac 200 mg twice daily did not blunt the antihypertensive effect of enalapril in 9 patients with hypertension. Two studies in black women also found that sulindac 200 mg twice daily for one month did not alter the antihypertensive effect of fosinopril 10 to 40 mg daily or lisinopril 10 to 40 mg daily (given with hydrochlorothiazide 25 mg daily). - ... 

There is evidence that most NSAIDs can increase blood pressure in patients taking antihypertensives, although some studies have not found the increase to be clinically relevant In various small studies, indometacin reduced the antihypertensive effects of the beta biockers. There is some evidence that piroxicam usually interacts similarly. Ibuprofen and naproxen have reduced the effect of beta blockers in some small studies but not others. Two isolated cases of hypertension have been reported with naproxen and ibuprofen in patients treated with propranolol and pindolol, respectively. Celecoxib, but not rofecoxib, inhibits the metabolism of metoprolol. Limited information su ests that normally di-... 

In patients with essential hypertension, indomethacin, given by in intramuscular injection at 1 mgkg increases blood pressure and total peripheral vascular resistance associated with diminution of cardiac output". However, reports that indomethacin, given orally at 75-200 mg day for 4-7 days, increases blood pressure in patients with untreated, uncomplicated, essential hypertension contrasts with reports that it does not . Cyclo-oxygenase inhibitors, indomethacin and ibuprofen, were also without effect on blood pressure in patients with renovascular hypertension . Yet, in two siblings with renin-dependent hypertension and aldosteronism, the administration of indomethacin at 250 mg day for 16 days was found to lower blood pressure and plasma renin activity, despite promoting slight retention of salt and water ... 

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