Spironolactone Aspirin

Underexcretion of urate is caused by all diuretics (except spironolactone), aspirin, ethambutol, pyr-azinamide, nicotinic acid, and alcohol (which increases urate synthesis and also causes a rise in blood lactic acid that inhibits tubular secretion of urate). The diagnosis of gout ideally requires the demonstration of negatively birefringent needle-shaped crystals in synovial fluid (monosodium urate monohydrate crystals), not just elevated serum urate. 

The administration of spironolactone (Aldactone) interferes in the determination of 11-hydroxy corticosteroid by methods that depend on formation of fluorescence in strong sulfuric acid (W15). In 5 patients, the administration of the drug produced as much as a 5-fold increase in the apparent plasma cortisol levels. Aspirin interferes in the determinations of homovanillic acid (HVA) by a fluorometric method. The HVA fluorophore occurs at 320 nm and 420 nm, and acetylsalicylic acid produces fluorescence at 305 to 405 nm (H12). 

Drugs that may affect aspirin include activated charcoal, ammonium chloride, ascorbic acid or methionine, antacids and urinary alkalinizers, carbonic anhydrase inhibitors, corticosteroids, and nizatidine. Drugs that may be affected by aspirin include alcohol, ACE inhibitors, anticoagulants (oral), beta-adrenergic blockers, heparin, loop diuretics, methotrexate, nitroglycerin, NSAIDs, probenecid and sulfinpyrazone, spironolactone, sulfonylureas and exogenous insulin, and valproic acid. 

Aspirin has been shown to slightly reduce the natriuretic effect of spironolactone in healthy individuals, possibly by reducing active renal tubular secretion of canrenone, the active metabolite of spironolactone. However, the hypotensive effect of spironolactone and its effect on urinary potassium excretion in hypertensive patients is apparently not affected. Until more clinical data are available on this potential interaction, patients receiving both drugs should be monitored for signs and symptoms of decreased clinical response to spironolactone [65]. 

ASPIRIN POTASSIUM-SPARING DIURETICS 1 efficacy of spironolactone Uncertain Watch for poor response to spironolactone... 

Enalapril, paracetamol, sotalol, dipyrone, vancomycin, captopril, fluconazole, cefazolin, metoprolol, aspirin, ticlopidine, prednisolone, propranolol, digoxin, sildenafil, furosemide, dexamethasone, carvedilol, ketoprofen, nifedipine, terbinafine, acenocoumarol, spironolactone/urine HPLC DAD Column LiChroCART Purospher STAR, RP-18e (250 x 4 mm, 5 pm) Mobile phase MeOH ACN 0.05 % TFA in water (gradient elution) Detection DAD X = 200 50 nm Adjusted to pH 7.0, protein precipitation LOD 0.01-1.44 pg/mL LOQ 0.04-4.35 pg/mL [72]... 

In low dosages (up to 2 g/day), aspirin reduces urate excretion and blocks the effects of probenecid and other uricosuric agents (22,23). However, in 11 patients with gout, aspirin 325 mg/day had no effect on the uricosuric action of probenecid (22). In higher dosages (over 5 g/ day), salicylates increase urate excretion and inhibit the effects of spironolactone, but it is not clear whether these phenomena are of importance. 

The renal tubular secretion of canrenone, the main metabolite of spironolactone, is blocked by aspirin (22), abolishing the diuretic response, although the antihypertensive effect is apparently not affected (23). 

Holhfield JW. Failure of aspirin to antagonize the antihypertensive effect of spironolactone in low-renin hypertension. South Med J 1976 69(8) 1034-6. 

Apart from the valuable benefit of aldosterone antagonism in hypertension, MR blockade has been shown to substantially reduce both morbidity and mortality among patients with severe chronic heart failure (CHF) and post-myocardial infarction (MI) in clinical trials [17, 18]. The Randomized Aldactone Evaluation Study (RALES) has shown that 26 mg spironolactone on average per day on top of existing standard therapy [i.e. an angiotensin-converting enzyme (ACE) inhibitor, aspirin and a loop diuretic] given to patients with severe heart failure (New York Heart Association class III or IV, left ventricular ejection fraction <35%) results in 30%... 

Simultaneous acebutolol, acetazolamide, acetophenetidin, adrenosterone, aldosterone, amitriptyline, androsten-3,17-dione, aspirin, carbamazepine, cephalothin, chlorothiazide, dehydrocorticosterone, deoxycorticosterone, deo cortisol, desipramine, dexamethasone, diazepam, equilenin, estradiol, estriol, estrone, fluorometholone, furosemide, hydrochlorothiazide, hydroxycorticosterone, hydroxyprogesterone, hydroxyprogesterone, imip-ramine, indomethacin, methylhydroxyprogesterone, methylprednisolone, nandrolone, nordiazepam, nortriptyline, pheniramine, phenobarbital, phenytoin, prednisolone, prednisone, primidone, probenecid, progesterone, quinine, spironolactone, testosterone, theophylline, triamcinolone, tripelennamine... 

Most of the renal tubular reabsorption ofU occurs in the proximal tubule. Nevertheless, Id retention can be increased by any diuretic that leads to depletion of Na, particularly the thiazides (see Chapter 28). Renal excretion can be increased by administration of osmotic diuretics, aceta-zolamide or aminophylline, and triamterene. Spironolactone does not increase the excretion of LiL Some nonsteroidal anti-inflammatory agents can facilitate renal proximal tubular resorption of Id and thereby increase concentrations in plasma to toxic levels. This interaction appears to be particularly prominent with indomethacin, but also may occur with ibuprofen, naproxen, and COX-2 inhibitors, and possibly less so with sulindac and aspirin. A potential drug interaction can occur with angiotensin-converting enzyme inhibitors, causing lithium retention (see Chapter 29). 

Sabidal S.R. Choline theophyllinate Sachicoron Mepenzolate bromide Sachol - Choline salicylate Sadamin -Xanthinol niacinate Sadocort Triamcinolone Sadoreum - Indomethacin Safitex Tolmetin Sagamicin Micronomicin Sagisal Spironolactone Saicil Ampicillin Saiclate - Cyclandelate Sainosine Trimetazidine St, Joseph Aspirin St. Joseph Aspirin Acetaminophen St. Joseph Cough Syrup - Dextromethorphan hydrobromide... 

The antihypertensive effects of spironolactone in patients with hypertension were unaffected by anti-inflammatory doses of aspirin in one small study, although there is evidence that these doses of aspirin reduce the spironolactone-induced loss of sodium in the... 

In another study in 7 patients with ascites due to liver cirrhosis, pre-treatment with two doses of aspirin 900 mg reduced the natriuretic effect of spironolactone 300 mg daily by 33%. However, there was no significant change in urinary output. ... 

An adequately but not extensively documented interaction. Despite the results of the studies showing a reduced natriuretic effect, the small study in hypertensive patients shows that the blood pressure-lowering effects of spironolactone might not be affected by anti-inflammatory doses of aspirin. In general, concurrent use need not be avoided, but if the diuretic response to spironolactone is less than expected consider this interaction as a cause. 

None of these studies looked at the effects of low-dose aspirin on spironolactone. Nevertheless, it is likely that the proven protective cardi-... 

There is much evidence of the nephrotoxicity of aspirin (140 ). Administration of aspirin (4 g daily) was associated with a rise in plasma creatinine (average increase 38%) and a fall in creatinine clearance (average decrease 25%). These changes were observed in 8 of 9 patients with rheumatoid arthritis and 10 of 11 healthy volunteers. There was no change in the clearance of chromium edetate (150 ). In another study aspirin produced similar changes in plasma creatinine and creatinine clearance. However, the blood urea was also increased and the inulin clearance was reduced in parallel with the creatinine clearance, suggesting that glomerular filtration was reduced (151 =). Aspirin also reduces the urinary excretion of canrenone, a metabolite of spironolactone. This effect may be caused by competition for active renal tubular secretion (152). 

Aspirin inhibits the renal effects of spironolactone on water and electrolyte balance, and inhibition of the active tubular secretion of the metabolite canienone has been postulated as a mechanism (152). 

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