Which one of the following statement is false about NSAIDs? (AIIMS Nov 2009)
|A||Acetylsalicylic acid is an irreversible inhibitor of COX enzyme|
|B||Salicylic acid reduces in vivo synthesis of prostaglandins|
|C||Duration of action of aspirin is primarily related to the pharmacokinetic clearance of the drug from the body|
|D||Antiplatelet effect of low-dose aspirin is related to presystemic COX inhibition|
a. Inhibition of cyclooxygenase (COX), the enzyme responsible for the biosynthesis of prostaglandins and certain related autocoids, generally is thought to be a major facet of the mechanism of action of NSAIDs. Aspirin covalently modifies both COX-1 and COX-2 thus resulting in an irreversible inhibition of cyclooxygenase activity.
b. This is an important distinction for aspirin, as the duration of the effects of aspirin is related to the turnover rate of cyclooxygenases in different target tissues. Platelets are especially susceptible to prolong.
c. Aspirin-mediated, irreversible inactivation of cyclooxygenase because they have little or no capacity for protein synthesis and thus cannot regenerate the lost cyclooxygenase enzyme.
d. Hence, single dose of aspirin will inhibit the platelet cyclooxygenase for the life of the platelet (8-11 days). A daily dose of aspirin as small as 40 mg is sufficient to produce the effect.
e. The ability of platelets to be inhibited by such low dose of aspirin is related to the presystemic inhibition of the cyclooxygenase in the portal circulation before the aspirin is de acetylated to salicylate in the liver.
f. In contrast to aspirin, salicylic acid has no acetylating capacity. But like aspirin it reduces the synthesis of prostaglandins in vivo.