Hypertension NSAID effect

Many centres prefer to avoid using NSAIDs in any patient with liver disease because of their side-effect profile. However, if the liver disorder is purely cholestatic in origin and the disease has not progressed to cirrhosis and portal hypertension, NSAIDs may be an option. Any risk-benefit assessment should consider the potential risk of hepatotox-icity, albeit rare. There are no specific contraindications in this patient because they are not cirrhotic, do not have deranged clotting, and are unlikely to be at increased risk of deteriorating renal function. If deemed necessary an NSAID could be used cautiously. 

When linezolid is used with antiplatelet drugs such as aspirin or die NSAIDs (see Chap. 18) diere is an increased risk of bleeding and thrombocytopenia When administered widi die MAOIs (see Chap. 31) the effects of the MAOIs are decreased. There is a risk of severe hypertension if linezolid is combined widi large amounts of food containingtyramine (eg, aged cheese, caffeinated beverages, yogurt, chocolate, red wine, beer, pepperoni). 

The COX-2 enzyme is also produced normally in the kidney thus COX-2 inhibitors exert renal effects similar to those of conventional NSAIDs. Both drug classes may increase sodium reabsorption and fluid retention and can provoke renal insufficiency and hyperkalemia. COX-2 inhibitors should be used with caution in patients with heart failure or hypertension. 

Indomethacin was used traditionally, but its relative cyclooxygenase-1 (COX-1) selectivity theoretically increases its gastropathy risk. Thus other generic NSAIDs may be preferred. Adverse effects of NSAIDs include gastropathy (primarily peptic ulcers), renal dysfunction, and fluid retention. NSAIDs generally should be avoided in patients at risk for peptic ulcers, those taking warfarin, and those with renal insufficiency or uncontrolled hypertension or heart failure. 

Patients should be asked if they are having adverse effects from their medications. They should also be monitored for any signs of drug-related effects, such as skin rash, headaches, drowsiness, weight gain, or hypertension from NSAIDs. 

Celecoxib (Celebrex) and rofecoxib (Vioxx) are highly selective COX-2 inhibitors. Because of this, they produce less erosion of the GI mucosa and cause less inhibition of platelet aggregation than do the nonselective COX inhibitors. Short-term (6 months-to a year) clinical trials have shown that celecoxib and rofecoxib produce less GI toxicity than nonselective NSAIDs. However, serious GI bleeding and ulceration have occurred in patients taking these drugs, and long-term prospective studies of their safety have yet to be completed. Like the nonselective NSAIDs, the selective COX-2 inhibitors can produce renal side effects such as hypertension and edema. 

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. 

The coxibs continue to be investigated to determine whether their effect on prostacyclin production could lead to a prothrombotic state. The frequency of other adverse effects approximates that of other NSAIDs. Celecoxib causes no more edema or renal effects than other members of the NSAID group, but edema and hypertension have been documented. 

Rofecoxib, a furanose derivative, is a potent, selective COX-2 inhibitor (Table 36-1). In the USA, rofecoxib is approved for osteoarthritis and rheumatoid arthritis, and it also appears to be analgesic and antipyretic—in common with other NSAIDs. This drug does not inhibit platelet aggregation and appears to have little effect on gastric mucosal prostaglandins or lower gastrointestinal tract permeability. At high doses it is associated with occasional edema and hypertension. Other toxicities are similar to those of other coxibs. 

Other measures include the clinician s global assessment based on the patient s history of activities and limitations caused by OA, the Western Ontario and McMaster Universities Arthrosis Index, Stanford Health Assessment Questionnaire, and documentation of analgesic or NSAID use. Patients should be asked if they are having adverse effects from their medications. They should also be monitored for any signs of drug-related effects, such as skin rash, headaches, drowsiness, weight gain, or hypertension from NSAIDs. 

ANTI HYPERTENSIVES AND HEART FAILURE DRUGS NS AIDs 1 hypotensive effect, especially with indometacin. The effect is variable amongst different ACE inhibitors and NSAIDs, but is most notable between captopril and indometacin NSAIDs cause sodium and water retention and raise BP by inhibiting vasodilating renal prostaglandins. ACE inhibitors metabolize tissue kinins (e.g. bradykinin) and this may be the basis for indometacin attenuating hypotensive effect of captopril Monitor BP at least weekly until stable. Avoid co administering indometacin with captopril... 

The shift in hemostatic balance toward a prothrombotic state might not be the only mechanism by which COX-2 inhibitors could increase the risk of cardiovascular adverse effects. In fact, non-selective NSAIDs can raise blood pressure and antagonize the hypotensive effect of antihypertensive medications to an extent that may increase hypertension-related morbidity (55,56). The problem is clinically relevant, as arthritis and hypertension are common co-morbid conditions in elderly people, requiring concurrent therapy. 

Intravenous administration of indometacin increases blood pressure, coronary vascular resistance, and myocardial oxygen demands, decreasing coronary flow. A controlled short-term study showed that indometacin increased blood pressure in patients with mild untreated essential hypertension (SEDA-17, 108). In view of the increasing use of parenteral administration, the acute hemodynamic effects of indometacin may now occur more often, especially in the elderly (5). The mechanism is poorly understood, but apparently a direct action is exerted on the resistance vessels in various regions. This is probably independent of indometacin s action on prostaglandin formation. The chnical relevance is largely unknown, but other NSAIDs should probably be prescribed for patients with occlusive vascular diseases affecting the cerebral and/or coronary vessels. 

Another meta-analysis provided more complete and useful results (23). Its primary aim was to produce an estimate of the overall effect of NSAIDs on blood pressure, and its secondary aims were to evaluate the mechanisms by which NSAIDs alter blood pressure and to determine susceptibility factors. Moreover, as NSAIDs have been associated with raised blood pressure in normotensive individuals and in both treated and untreated hypertensive subjects, the authors tried to discover different effects in these subgroups. Finally, they studied whether different NSAIDs alter blood pressure to the same degree. 

All NSAIDs interfere with hypertension control in patients taking diuretics, beta-blockers, or vasodilators, although contrasting data have been published on the effects of these drugs on blood pressure (233). Moreover, they interact diversely with different... 

Antihypertensive drugs Indometacin Reduction in hypotensive effect, probably related to impaired prostaglandin synthesis (causing salt and water retention) and vascular prostaglandin synthesis (causing vasoconstriction) Avoid all NSAIDs in treated hypertensive patients if possible if not, use sulindac preferentially may need additional antihypertensive therapy... 

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. 

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