Antihypertensive drugs NSAIDs

The NSAIDs prolong bleeding time and increase the effects of anticoagulants, lithium, cyclosporine, and the hydantoins. These dru may decrease the effects of diuretics or antihypertensive drug >. Long-term use of the NSAIDs with acetaminophen may increase the risk of renal impairment. 

The hypotensive effects of most antihypertensive dru are increased when administered with diuretics and other antihypertensives. Many dnigp can interact with the antihypertensive drugs and decrease their effectiveness (eg, antidepressants, monoamine oxidase inhibitors, antihistamines, and sympathomimetic bronchodilators). When the ACE inhibitors are administered with the NSAIDs, their antihypertensive effect may be decreased. Absorption of the ACE inhibitors may be decreased when administered with the antacids. Administration of potassium-sparing diuretics or potassium supplements concurrently with the ACE inhibitors may cause hyperkalemia. When the angiotensin II receptor agonists are administered with... 

Lithium intoxication can be precipitated by the use of diuretics, particularly thiazides and metola-zone, and ACE inhibitors. NSAIDs can also precipitate lithium toxicity, mainly due to NSAID inhibition of prostaglandin-dependent renal excretion mechanisms. NSAIDs also impair renal function and cause sodium and water retention, effects which can predispose to interactions. Many case reports describe the antagonistic effects of NSAIDs on diuretics and antihypertensive drugs. The combination of triamterene and indomethacin appears particularly hazardous as it may result in acute renal failure. NSAIDs may also interfere with the beneficial effects of diuretics and ACE inhibitors in heart failure. It is not unusual to see patients whose heart failure has deteriorated in spite of increased doses of frusemide who are also concurrently taking an NSAID. 

In combination with potassium-sparing diuretics severe hyperkalaemia may occur. The elimination of lithium is prolonged. Non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the antihypertensive effect of ACE inhibitors. 

Corticosteroids interact with barbiturates, carbamazepine, phenytoin, primidone, frusemide, thiazide, NSAIDs, antidiabetics, and antihypertensive drugs. Benzquinamide hydrochloride is incompatible with chlordiazepoxide, diazepam, and some barbiturates. Care should be exercised when handling bisacodyl to avoid contact with skin and mucosal membranes. 

P-adrenoceptor blockers lose some antihypertensive efficacy when nonsteroidal anti-inflammatory drugs (NSAIDs), especially indomethacin, are coadministered the effect involves inhibition of production of vasodilator prostaglandins by the kidney leading to sodium retention. 

Prostaglandin synthesis. Nonsteroidal anti-inflammatory drugs (NSAIDs), e.g. indomethacin, attenuate the antihypertensive effect of p-adrenoceptor blockers and of diuretics, perhaps by inhibiting the synthesis of vasodilator renal prostaglandins. This effect can also be important when a diuretic is used for severe left ventricular failure. 

The antihypertensive effect of beta-blockers can be impaired by the concurrent administration of some nonsteroidal anti-inflammatory drugs (NSAIDs), possibly because of inhibition of the synthesis of renal vasodilator prostaglandins. This interaction is probably common to all beta-blockers, but may not occur with aU NSAIDs for example, sulindac appears to affect blood pressure less than indometacin (405-407). 

NSAIDs inhibited the effects of aU antihypertensive drug categories. However, in patients taking beta-block-ers and vasodilators, NSAIDs produced a greater increase in supine mean blood pressure than in patients taking diuretics, but only the pooled inhibitory effect of NSAIDs on the effects of beta-blockers achieved statistical significance. When the data were analysed by tjrpe of NS AID the meta-analysis showed that aU NSAIDs increased supine blood pressure, and that piroxicam, indometacin, and ibuprofen produced the most marked increases. However, only piroxicam had a statistically significant effect with respect to placebo. Aspirin,... 

This study also had two main limitations first, most of the trials were small, which precluded definitive conclusions about the effects of individual NSAIDs or individual antihypertensive drug classes secondly, in most studies, therapy was short term and the patients were relatively young, making generalization of the results difficult, as NSAIDs are most often prescribed long term and for elderly people. 

The impact of NSAIDs on blood pressure in elderly people has been evaluated in three epidemiological studies, with similar findings (SEDA-19, 92). The use of NSAIDs was significantly associated with hypertension or the use of antihypertensive drugs. Reliable data are available for hypertension in the elderly. Recent users of NSAIDs have a 1.7-foId increase in the risk of initiating antihypertensive therapy compared with non-users, and the use of NSAIDs significantly predicts the presence of hypertension (OR = 1.4 95% Cl = 1.1,1.7) (21). 

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... 

Direct information seems to be limited to this study but what occurred is consistent with the way indometacin reduces the effects of many other different antihypertensives (e.g. see ACE inhibitors + NSAIDs , p.28, and Beta blockers + Aspirin or NSAIDs , p.835). It apparently does not affect every patient. If indometacin is added to established treatment with prazosin, be alert for a reduced antihypertensive response. It is not known exactly what happens in patients taking both drugs long-term, but note that with other interactions between antihypertensives and NSAIDs the effects seem to be modest. The manufacturers say that prazosin has been given with indometacin (and also aspirin and phenylbutazone) without any adverse interaction in clinical experience to date. Other manufacturers also... 

For the effects of NSAIDs on other antihypertensive drug classes see ACE inhibitors , (p.28), calcium-channel blockers , (p.861) and thiazide diuretics , (p.956). 

Table 23.2 Summary of epidemiological studies and meta-analyses of the effect of NSAIDs on blood pressure in patients taking antihypertensive drugs...

NSAIDs can cause increases in blood pressure due to their effects on sodium and water retention. Various NSAIDs have been reported to reduce the efficacy of other antihypertensive drug classes, for example see ACE inhibitors + NSAIDs , p.28. It would therefore be prudent to monitor concurrent use of hydralazine and NSAIDs. 

The most potentially serious drug interactions include the concomitant use of NSAIDs with lithium, warfarin, oral hypoglycemics, high-dose methotrexate, antihypertensives, angiotensin-converting enzyme inhibitors, fi-blockers, and diuretics. 

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