Spironolactone tubular secretion

Quinidine inhibits the tubular secretion of digoxin which consequently raises the plasma digoxin concentration, which may be associated with toxicity. Certain other drugs also increase the digoxin concentration like verapamil, amiodarone, spironolactone etc. 

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]. 

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. 

Spironolactone inhibits the active tubular secretion of digoxin by about 25% and in some cases digoxin dosages may have to be reduced (295). 

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). 

Spironolactone increases steady-state digoxin concentrations by about 30%, probably by inhibiting the renal tubular secretion of digoxin by P glycoprotein. There may also be a pharmacodynamic interaction with digoxin. The clinical importance of these observations is uncertain (SEDA-9, 209). 

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). 

When ascites and edema become severe, diuretic therapy can be very useful. However, cirrhotic patients are often resistant to loop diuretics because of decreased secretion of the drug into the tubular fluid and because of high aldosterone levels. In contrast, cirrhotic edema is unusually responsive to spironolactone and eplerenone. The combination of loop diuretics and an aldosterone receptor antagonist may be useful in some patients. 

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