Heart failure NSAIDs

COX-2, cyclooxygenase-2 HF, heart failure NSAID, non-steroidal antiinflammatory drug. 

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. 

Although the risk of GI complications is relatively small with short-term therapy, coadministration with a proton pump inhibitor should be considered in elderly patients and others at increased GI risk. NSAIDs should be used with caution in individuals with a history of peptic ulcer disease, heart failure, uncontrolled hypertension, renal insufficiency, coronary artery disease, or if they are receiving anticoagulants concurrently. 

Nephron adaptation to chronic diuretic therapy NSAID use Heart failure... 

NSAID Heart failure Worsening of heart failure... 

Management of an acute attack of gout involves the use of high doses of nonsteroidal anti-inflammatory agents (NSAIDs). Colchicine is useful in patients with heart failure where the use of NSAIDs is contraindicated because of water retention. Allopurinol and other uricosuric agents are not indicated for acute attacks as they may aggravate the condition. The use of an intra-articular corticosteroid injection in gout is unlicensed. 

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. 

Cardiovascular safety. Both drug types promote salt retention, can exacerbate heart failure and tend to raise blood pressure. COX-2 selective drugs also appear to raise the risks of thrombotic events, notably stroke and myocardial infarction, and recent evidence suggests that non-selective NSAIDs also raise these risks, though it is unclear whether to the same degree. For both drug types, dose and duration of treatment appear to affect risk. 

These findings from special renal studies and the clinical trial data indicate that inhibition of Cox-2 does not eliminate the renal effects of NSAIDs because Cox-2-derived prostanoids are involved in normal renal function. However, the kidney contains considerably more Cox-1 than Cox-2, and the localization of the two isoforms is different It is not yet known whether the Cox-2 inhibitors will be safer in subgroups of patients prone to develop acute renal failure with NSAIDs, such as those patients with severe volume depletion, congestive heart failure, or hepatic cirrhosis with ascites (Bosch-Marce et al., 1999). Also, it is not known whether rare events, such as interstitial nephritis or papillary necrosis, will occur with long-term use of Cox-2 inhibitors, although studies in animals suggest that such events may be related to Cox-1 inhibition, since only Cox-1 is found in the papilla. Therefore, Cox-2 inhibitors may not produce these serious adverse effects (Khan etal., 1998). 

Chronic heart failure is typically managed by reduction in physical activity, low dietary intake of sodium (less than 1500 mg sodium per day), and treatment with vasodilators, diuretics and inotropic agents. Drugs that may precipitate or exacerbate CHF—nonsteroidal antiinflammatory drugs (NSAIDs), alcohol, (3-blockers, calcium channel-blockers and some antiarrhythmic drugs—should be avoided if possible. Patients with CHF complain of dyspnea on exertion, orthopnea, paroxysmal nocturnal dyspnea, fatigue, and dependent edema. 

History of hypersensitivity to aspirin or another NSAID, severe heart failure, patients with previous or active peptic ulceration... 

Systemic steroids (e.g. prednisolone) can also be used. These may be of use in patients with severe or polyarticular attacks or those with renal disease or heart failure which may preclude the use of NSAIDs or colchicine. 

Diclofenac is contraindicated in those with a history of hypersensitivity to aspirin or another NSAID, severe heart failure, patients with previous or active peptic ulceration, or porphyria. It should be avoided in pregnancy. It should be used with caution in patients with allergic disorders, renal, hepatic and cardiac impairment, the elderly, in lactation and in those with coagulation defects. 

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... 

PROGESTOGENS 1. ANALGESICS -NSAIDs 2. ANTI HYPERTENSIVES AND HEART FAILURE DRUGS - ACE inhibitors, angiotensin II receptor antagonists 3. DIURETICS — potassium-sparing t risk of hyperkalaemia Drospirenone (component of the Yasmin brand of combined contraceptive pill) is a progestogen derived from spironolactone that can cause potassium retention Monitor serum potassium weekly until stable and then every 6 months... 

Diuretics (commonly referred to as water pills ), which are used to treat heart failure and high blood pressure - a decreased effect of these drugs because NSAIDs cause fluid retention. 

NSAIDs should be avoided in patients with chronic renal insufficiency due to the risk of inducing further kidney damage. In patients at risk, acute renal feilure can occur after a single dose of drug. Risk fectors include dehydration, hypertension, congestive heart failure, concomitant use of angiotensin-converting enzyme inhibitors, and advanced age. 

Feenstra J, Grobbee DE, Mosterd A, Strieker BH. Adverse cardiovascular effects of NSAIDs in patients with congestive heart failure. Dmg Safety 1S>97 17 166-180. 

In a randomized comparison of celecoxib and diclofenac plus omeprazole, renal adverse events, including hypertension, peripheral edema, and renal insufficiency, were common and similar in the two groups (105). They occurred in the 24% of the patients who took celecoxib and in 31% of those who took diclofenac plus omeprazole. Among patients with renal impairment at baseline, 51% of those who took celecoxib and 41% of those who took diclofenac plus omeprazole had renal adverse events. Careful monitoring of renal function in patients taking COX-2 inhibitors or traditional NSAIDs is mandatory, especially in high-risk subjects (for example those with pre-existing renal disease, diabetes, or heart failure). 

However, these data are limited and must be interpreted with caution, since NSAIDs have significant toxic effects on the kidney only in patients at risk (that is those with volume depletion, heart failure, cirrhosis, intrinsic renal disease, and hypercalcemia), in whom the secretion of vasodilator prostaglandins is increased in an attempt to counteract the effect of increased renal vasoconstrictors, such as angiotensin II. 

In contrast, published case reports and case series have provided more insight into the potential nephrotoxicity associated with COX-2-selective inhibitors. Taken together, these case reports suggest that COX-2 inhibitors, like non-selective NSAIDs, produce similar and consistent renal adverse effects in patients with one or more risk factors that induce prostaglandin-dependent renal function (that is patients with renal and cardiovascular disease and taking a number of culprit medications, such as diuretics and ACE inhibitors). Acute renal insufficiency, disturbances in volume status (edema, heart failure), metabolic acidosis, hyperkalemia, and hyponatremia have been commonly described. The duration of treatment with COX-2 inhibitors before the development of chnically recognized renal impairment ranged from a few days to 3-4 weeks. Withdrawal of COX-2 inhibitors and supportive therapy most often resulted in resolution of renal dysfunction, but in some patients hemodialysis was required (102,108-112). 

Furosemide inhibits the absorption of indometacin (42), while the diuretic and hypotensive effects of most diuretics are blunted by indometacin and probably also other NSAIDs (43). Intravenous furosemide is commonly given to patients with acute heart failure to relieve pulmonary congestion. Symptomatic relief occurs before the onset of diuresis, and the beneficial effect is believed to result from a venodUator action of furosemide, which precedes its diuretic effect. This venodilator response is inhibited by indometacin, suggesting that it occurs through local prostaglandin release. 

A series of 11 spontaneously reported cases in which renal impairment was associated with the use of nimesulide has been described (17). The adverse events were represented by acute renal insufficiency n — 2), acute deterioration of chronic renal insufficiency n — 3), fluid retention n = 4), and oliguria and macro hematuria n = 1 each). The patients had a median age of 57 (range 17-81) years and six had some predisposing condition (chronic renal insufficiency, heart failure, diabetes, use of diuretics) to NSAID-induced functional renal impairment. Apart from one patient, nimesulide was taken for a very short time (less than 8 days). A favorable outcome ensued after withdrawal of therapy in aU patients. The acute deterioration of renal function described in these patients pointed to hemodynamically mediated renal impairment in all cases, with the exception of one man in whom interstitial nephritis was suspected. 

Much less is known about the risk of congestive heart failure with NSAIDs. The rate of hospitalization for congestive heart failure in more than 10 000 patients over 55 years of age during exposure to both diuretics and NSAIDs was compared with the rate in those exposed to diuretics alone (31). At mean follow up of 4.7 years, there was an increased risk of hospitalization when diuretics and NSAIDs were used concomitantly (RR = 1.8 95% Cl = 1.4, 2.4). 

In 600 elderly patients with documented congestive cardiac failure there was a possible or probable link between NSAIDs and heart failure in 27 cases (32). In some, the mechanism was apparently a reduction in the effect of furosemide. In others the NSAID may have caused an imbalance in circulatory homeostasis. Preexisting renal impairment was not observed in any of the 27 cases. This study suggests that in elderly people congestive heart failure may be a complication of NSAIDs. 

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