Aspirin renal clearance

Renal clearance of lithium is reduced about 25% by diuretics (eg, thiazides), and doses may need to be reduced by a similar amount. A similar reduction in lithium clearance has been noted with several of the newer nonsteroidal anti-inflammatory drugs that block synthesis of prostaglandins. This interaction has not been reported for either aspirin or acetaminophen. All neuroleptics tested to date, with the possible exception of clozapine and the newer atypical antipsychotics, may produce more severe extrapyramidal syndromes when combined with lithium. 

Drugs that alter the pH of urine can significantly affect the renal excretion of other drugs. Acid urine increases the effectiveness of mercurial diuretics. It also accelerates the excretion of basic drugs such as meperidine, tricyclic antidepressants, amphetamines, and antihistamines. Acidic drugs, such as aspirin, streptomycin, phenobarbital, sulfonamides, nalidixic acid, and nitrofurantoin have been shown to increase renal clearance in alkaline urine (61). The possible effects of urine pH on the renal excretion of drugs has been illustrated by the observation that if urine is rendered sufficiently alkaline, the excretion of amphetamine is markedly delayed and effective blood levels, after a single dose, can be maintained for several days (62). 

Aspirin and methotrexate compete for renal tubular secretion, and aspirin alters the systemic and renal clearances of intravenous methotrexate (131). However, the clinical relevance of this interaction is not clear. In one study, aspirin (mean dose 4.5 g) in 12 patients did not cause more toxicity than other NSAIDs taken by 22 other patients (132). 

Antacids and food can delay and decrease the absorption of tolmetin. NSAIDS are known to decrease renal clearance of lithium carbonate, thus increasing lithium serum levels and risks of adverse effects. Concomitant use of tolmetin and aspirin may decrease plasma levels of tolmetin. 

Several NSAIDs, including aspirin, ibuprofen, and piroxicam, increase serum levels of methotrexate by interfering with its renal clearance. The adverse effects of methotrexate, including its hematotoxicity are predictably increased. The answer is (J). 

The damaging effects of aspirin and NSAIDs on the gut appear to be additive. The mechanisms behind the pharmacokinetic changes have not been resolved. Changes in the rates of absorption and renal clearance and competition for plasma protein binding have been proposed. 

A study in 15 patients with rheumatoid arthritis given a single 10-mg bolus dose of methotrexate, either with or without aspirin 975 mg four times daily, found that the methotrexate clearance was reduced by aspirin (systemic clearance about 16%, renal clearance of unbound methotrexate about 30%). Also the unbound traction of methotrexate was higher during aspirin use. Despite these changes no acute toxicity was seen. Another study found that aspirin did not atfect the pharmacokinetics of methotrexate. Yet another study found that, although aspirin did not alter the pharmacokinetics of methotrexate, it did increase the AUC of the metabolite 7-hy-droxy methotrexate. ... 

Renal clearance of methotrexate is inhibited by aspirin the increased serum levels of methotrexate can lead to bone marrow toxicity. 

The main interactions of aspirin and the salicylates were reviewed in SED VIII (p. 174). New papers have appeared on interactions with various anti-flammatory drugs, though data on indomethacin in this connection are contradictory (168 -172 ). There may be species differences in these interactions (172 ). Plasma concentrations of salicylate are markedly reduced (30—70%) by antacids as a result of increased urine pH and enhanced renal clearance of salicylate (173 ). In guinea pigs aspirin enhances the metabolism of paracetamol to the hepatotoxic metabolite which is excreted in the urine as paracetamol mercaptu-ric acid (174). This interaction may potentiate the toxicity of phenacetin and paracetamol. 

Probenecid is a uricosuric agent that blocks the tubular reabsorption of uric acid, increasing its excretion. Because of its mechanism of action, probenecid is contraindicated in patients with a history of uric acid stones or nephropathy. Probenecid loses its effectiveness as renal function declines and should be avoided when the creatinine clearance is 50 mL/minute or less. Its uricosuric effect is counteracted by low aspirin doses, which many patients receive for prophylaxis of coronary heart disease. 

Renal function impairment No changes were observed in the pharmacokinetics of dipyridamole or its glucuronide metabolite with creatinine clearances ranging from approximately 15 mL/min to more than 100 mL/min if data were corrected for differences in age. Avoid aspirin in patients with severe renal failure (glomerular filtration rate less than 10 mL/min). 

The arylpropionic acid derivatives are useful for the treatment of rheumatoid arthritis and osteoarthritis, for reduction of mild to moderate pain and fever, and for pain associated with dysmenorrhea. Side effects of the drugs are similar to but less severe than those described for the salicylates. Those who are sensitive to salicylates also may be sensitive to and have adverse reactions when taking ibuprofen and related drugs. Acute hypersensitivity to ibuprofen has been reported in patients with lupus. The hypersensitivity reaction to sulindac can be fatal. The use of sulindac has also been linked to cases of acute pancreatitis. The use of dimethylsulfoxide (DMSO) topically in combination with sulindac has been reported to induce severe neuropathies. The concurrent use of ibuprofen with aspirin reduces the antiinflammatory effects of both drugs. Ibuprofen is contraindicated in patients with aspirin sensitivity leading to bronchiolar constriction and in patients with an-gioedema. As with all NSAIDs, renal and liver function should be normal for adequate clearance of the drugs. 

Concurrent administration of aspirin reduces ketoprofen protein binding and increases its clearance. Salicylate also reduces the metabohc conversion of ketoprofen to its conjugates and their renal elimination, and enhances its conversion to non-conjugated metabohtes (15). 

Various NSAIDs, such as ibuprofen, indomethacin, ketoprofen, phenylbutazone, piroxicam, and oxyphenbutazone, can decrease renal creatinine and lithium clearance by their common inhibitory action on prostaglandin synthesis. Aspirin (acetylsalicylic acid) and sulindac have not been found to increase lithium plasma steady-state concentrations. ... 

Acute renal failure developed in a woman taking captopril when she started to take aspirin for arthritis. Renal function improved when both were stopped. However, in a re-analysis of data from the Hypertension Optimal Treatment (HOT) study, long-term low-dose aspirin 75 mg daily had no effect on changes in serum creatinine, estimated creatinine clearance or the number of patients developing renal impairment, when compared with placebo. Of 18 790 treated hypertensive patients, 41% receiv an ACE inhibitor. ... 

No change in serum lithium levels was seen in 7 patients taking lithium when they were given aspirin 975 mg four times daily for 6 days. Another report states that aspirin 600 mg four times daily had no effect on the absorption or renal excretion of single doses of lithium carbonate given to 6 healthy subjects. Further reports describe no change in serum lithium levels with lysine aspirin, intravenous aspirin, or intravenous sodium salicylate. However, lithium clearance was slightly reduced by 22% by intravenous sodium salicylate, and a study in one healthy subject found a 32% increase in mean serum-lithium levels from 0.41 to 0.54 mmol/L after 5 days of oral aspirin treatment (975 mg four times daily for 2 days, then 650 mg four times daily for 3 days). ... 

Aspirin is rapidly hydrolyzed in the plasma to salicylic acid such that plasma levels of aspirin are essentially undetectable 1-2 hours after dosing. Salicylic acid is primarily conjugated in the liver to form salicyluric acid. Salicyhc acid has a plasma half-life of approximately 6 hours. The clearance of aspirin is limited by the abihty of the liver to conjugate salicyclic acid. After conjugation by the liver, the metabolites undergo renal excretion. 

Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the clearance of MTX (121). However, the effect is relatively small and does not appear to have a clinically significant effect (118,122,123). Conversely, if NSAIDs induce acute renal failure, high levels of MTX and toxicity can be encountered. We have observed two patients who developed severe MTX-induced leukopenia associated with NSAID-induced renal failure. 

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). 

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