Aspirin protein binding

Avoid aspirin, as it may increase free T4 and T3 levels by interfering with plasma-protein binding ° Fluid resuscitation... 

Distribution - Valproic acid is rapidly distributed. Volume of distribution of total or free valproic acid is 11 or 92 L/1.73 m, respectively. Valproic acid has been detected in CSF (approximately 10% of total concentrations) and milk (about 1% to 10% of serum concentrations). Therapeutic range is commonly considered to be 50 to 100 mcg/mL of total valproate. The plasma protein binding of valproate is concentration-dependent. Protein binding of valproate is reduced in the elderly, in patients with chronic hepatic diseases, in patients with renal impairment, and in the presence of other drugs (eg, aspirin). Conversely, valproate may displace certain protein-bound drugs (eg, phenytoin, carbamazepine, warfarin, tolbutamide). 

Iopanoic acid is as potent a uricosuric agent as probenecid and this effect might explain some renal complications aspirin reduces the uricosuric effect but can also impair X-ray visualization because of competition at plasma protein-binding sites. Fluctuations of serum urate after oral cholecystography can interfere with diagnostic tests and even precipitate an attack of gout (578). 

Salicylates Interference with renal excretion of drugs that undergo active tubular secretion. Salicylate renal excretion dependent on urinary pH when large doses of salicylate used. Aspirin (but not other salicylates) interferes with platelet function. Large doses of salicylates have intrinsic hypoglycemic activity. Salicylates may displace drugs from plasma protein binding sites. Carbonic anhydrase inhibitors [NE] Increased acetazolamide serum concentrations increased salicylate toxicity due to decreased blood pH. 

B. Aspirin was competing for protein binding with digoxin, leading to increased concentrations of free digoxin and thus more free digoxin eliminated by the kidneys. 

For a displacement interaction to become clinically important, a second mechanism usually operates sodium valproate can cause phenytoin toxicity because it both displaces phenytoin from its binding site on plasma albumin and inhibits its metabolism. Similarly aspirin and probenecid (and possibly other nonsteroidal anti-inflammatory drugs) displace the folic acid antagonist methotrexate from its protein-binding site and reduce its rate of active secretion by the renal tubules the result is serious methotrexate toxicity. 

Aspirin displaces sodium valproate from protein binding sites (112) and reduces its hepatic metabolism (113). 

Orr JM, Abbott FS, Farrell K, Ferguson S, Sheppard I, Godolphin W. Interaction between valproic acid and aspirin in epileptic children serum protein binding and metabolic effects. Clin Pharmacol Ther 1982 31(5) 642-9. 

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). 

Concomitant use of heparin and oral anticoagulants can increase the risk for bleeding due to the antiplatelet effect of aspirin. In addition, use with alcohol can increase the risk of Gl bleeding. / spirin displaces a number of drugs (e.g., tolbutamide, nonsteroidal anti-inflammatory drugs [NSAIDs], methotrexate, phenytoin, and probenecid) from protein binding sites in the blood. Corticosteroid use can reduce serum salicylate levels by increasing the clearance of aspirin. 

The most frequent side effects arc gastric di.strcss and headache. It has also been as.sociated with peptic ulceration, blood disorders, and possible deaths. The side effects appear to be dose related and sometimes can be minimized by rcduc-ing the dose. It is not recommended for use in children because of po.ssible interference with resistance to infection. Like many other acidic compounds, it circulates bound to blood protein, thus requiring caution in the concurrent use of other protein-binding drugs. Indomethacin is recummended only for patients who cannot tolerate aspirin and in place of phenylbutazone in long-term therapy, for which it appears to be le.ss hazardous than coitico.steroid ur phenylbutazone. 

Drugs can compete for the same protein binding sites and this is a form of drug interaction. A well-known and important example is that of warfarin and aspirin. Warfarin is an anticoagulant, which binds extensively to plasma proteins, and this is taken into account when dosages are worked out. Aspirin taken with warfarin competes for the same... 

If warfarin and aspirin are used simultaneously, both drugs appear in the plasma in higher than expected concentrations due to competition for plasma protein binding. This will increase the pharmacological activity of both drugs, but the action of warfarin is of most importance. 

An interaction involving protein binding displacement may occur with aspirin. 

Children given antipyretic doses of aspirin co-administered with valproate were found to exhibit a decrease in protein binding and an inhibition of the metabolism of valproate. The common use of aspirin should alert to the need for caution if these drugs are co-administered. Interaction with other non-steroidal anti-inflammatory drugs (NSAIDs) may not be so prominent. 

Aspirin i plasma protein binding of methotrexate (a relatively minor contribution to the interaction) and the renal excretion of high doses of methotrexate. Salicylates compete with methotrexate for renal elimination... 

Salicylates are highly bound to plasma protein albumin, with binding being concentration dependent. At low therapeutic concentrations of 100 pg/mL, approximately 90% of aspirin is plasma protein bound, whereas at higher concentrations of approximately 400 pg/mL, only 76% binding is observed. Plasma protein binding is a major factor in the drug interactions observed for salicylates. 

Aspirin displaces warfarin from protein-binding sites and will increase the ehent s bleeding therefore, the nurse should question administering the aspirin. 

---