Aspirin binding

L. Aarons, R Cbfton, G. Fleming, M. Rowland, Aspirin Binding and the Effect of Albumin on Spontaneous and Enzyme-Catalysed Hydrolysis , J. Pharm. Pharmacol. 1980, 32, 537-543. 

More recently, Kintz (personal communication) has attempted to analyze for aspirin in hair after taking 500 mg/d for two weeks. Approximately 1 ng of aspirin/mg of hair was observed. A similar user of cocaine would be considered a heavy cocaine user. If aspirin binding to hair was as strong as cocaine, 10 to 100 times more aspirin would have been expected. 

The best-known NSAID is aspirin, acetylsalicylic acid. Aspirin binds to the COX active site, and, once bound, can acetylate Ser530 (Fig. 5) [1]. Acetylation of this active site serine causes irreversible COX inactivation. Curiously, the hydroxyl group of Ser530 is not essential for catalysis, but acetylated Ser530 protrudes into the COX site and interferes with the binding of AA. 

In 1 969, Dr. John Vane and his collaborators at the Royal College of Surgeons in London discovered that aspirin inhibited production of prostaglandins by injured tissue. Eventually it was shown that this happens because aspirin binds to cyclooxygenase, inhibiting the conversion of arachidonic acid to PCCj. This stops the production of prostaglandins, resulting in a reduction of... 

Because aspirin binds irreversibly with cyclooxygenase it inhibits the enzyme in platelets for their entire lifespan, since platelets are unable to... 

Another important function of albumin is its ability to bind various ligands. These include free fatty acids (FFA), calcium, certain steroid hormones, bilirubin, and some of the plasma tryptophan. In addition, albumin appears to play an important role in transport of copper in the human body (see below). A vatiety of drugs, including sulfonamides, penicilhn G, dicumarol, and aspirin, are bound to albumin this finding has important pharmacologic implications. 

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

The answer is c. (Hardman, pp 887, 889.) Bile acid-binding resins bind more than just bile acids, and binding of simvastatin to cholestyramine is the most likely mechanism for decreased Gl absorption. Cholestyramine may also bind to several other drugs, including digoxin, benzothiadiazides (thiazides), warfarin, vancomycin, thyroxine (T4), and aspirin. Medications should be given one hour before or four hours after cholestyramine. 

The hydrolysis of acetylsalicylic acid (aspirin) has also been described, and it involves the rapid acetylation of Lys199 [123], This reactive site also involves Trp214 and has been called the U-site [124], Drugs that inhibit the hydrolysis of substituted acetylsalicylic acids by HSA and decrease the fluorescence intensity of Trp214 are referred to as U-type drugs (e.g., sulfinpyrazone and warfarin). Because U-type drugs also bind to the site know as site I (which overlaps with subdomain IIA), the U-site and I-site are believed to overlap. Lysine residues also appear to be involved in the /3-lactamase activity of HSA [125],... 

Y. Kurono, H. Yamada, K. Ikeda, Effects of Drug Binding on the Esterase-Like Activity of Human Serum Albumin. V Reactive Site towards Substituted Aspirins , Chem. Pharm. Bull. 1982, 30, 296 - 301. 

Aspirin Aspirin is poorly bound to plasma proteins and its apparent volume of distribution is low (10 L). Its metabolite, salicylic acid, is highly bound to plasma proteins, but its binding is concentration-dependent (nonlinear). At low concentrations (less than 100 mcg/mL), approximately 90% of salicylic acid is bound to albumin. Salicylic acid is widely distributed to all tissues and fluids in the body, including the CNS, breast milk, and fetal tissues. 

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). 

C. Aspirin inhibits platelet cyclooxygenase. Abciximab, a monoclonal antibody, binds to and inhibits the platelet glycoprotein Ilb/IIIa receptor. Dipyridamole inhibits platelet cyclic AMP phosphodiesterase and raises cyclic AMP levels. Eptifibatide binds to the glycoprotein Ilb/IIIa complex. 

Multiple drug interactions can occur with the TCA drugs. Because of their high degree of binding to plasma proteins, competition for binding sites can exist between TCAs and phenytoin, aspirin, phenothiazines. 

Rapidly and complefely absorbed from G1 fracf enferic-coafed absorpfion delayed recfal absorpfion delayed and incomplefe. Profein binding High. Widely disfribufed. Rapidly hydrolyzed fo salicylafe. Half-life 15-20 min (aspirin) 2-3 hr (salicylafe af low dose) more fhan 20 hr (salicylafe af high dose). 

In adults, TCAs are highly protein-bound medications. At any one time 75%-95% of the drug in the body will be bound to circulating ttj glycoprotein. Competition for binding sites on ttj glycoprotein by drugs such as aspirin, phenytoin, and some phenothiazines... 

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