Which one of the following statements is not true about NSAIDs?
Ans. is 'c' i.e., Duration of action of aspirin is primarily related to pharmacokinetic clearance of the drug form the body Inhibition of COX by Aspirin o Aspirin inhibits COX irreversibly by acetylating one of its serine residues; return of COX activity depends on synthesis offresh enzyme (not on the pharmacokinetic clearance of the drug). On the other hand, Other NSAIDs are competitive and reversible inhibitors of COX, return of activity depends on their dissociation from the enzyme which in turn is governed by the pharmakokinetic clearance from the body. o Duration of action of aspirin is dependent on synthesis of fresh COX. o Duration of action of other NSAIDs is dependent on pharmakinetic clearance of the drug from the body. o Salicylates are salts of salicylic acid, e.g., methyl saiicylate, sodium salicylate, acetyl salicylic acid (aspirin). Salicylates are rapidly metabolized to salicylic acid which is the active form (reduces PG synthesis). However, in contrast to aspirin, salicylic acid has no acetylating capacity (as it does not contain acetyl group). Therefore, it inactivates the COX reversibly (irreversible inhibition requires acetylation of COX). Antiplatelet action of aspirin o Antiplatelet effect of low dose aspirin is related to presystemic inhibition of cyclooxygenase. Aspirin inhibits the synthesis of TXA2 in platelets as well as PGI2 in vessels wall by inhibiting enzyme cyclooxygenase. However, at low doses aspirin has platelet antiaggregatory effect due to inhibition of synthesis of TXA2 because : ? i) Platelets are exposed to aspirin in the poal circulation before it is deacetylated during first pass metabolism (presystemic metabolism) in liver. Here it inactivates COX and inhibits the synthesis of TXA2 As aspirin is metabolized in liver very little aspirin reaches the systemic circulation to inhibit PGI2 synthesis. ii) Aspirin irreversibly inhibit cycloxygenase of platelets. Platelets do not have nuclei, they cannot synthesize fresh enzyme. Therefore, low doses of aspirin suppresses TXA2 formation till fresh platelets are formed. On the other hand, intimal cells (endothelium) of vessel wall can synthesize fresh COX, activity returns rapidly and PGI2 synthesis restas rapidly.
Acetyl salicylic acid is an irreversible inhibitor of COX enyzme
Salicylic acid reduces in vivo synthesis of prostaglandins
Duration of action of aspirin is primarily related to the pharmocokinetic clearance of the drug from the body
Anitplatelet effect of low-dose aspirin is related to presystemic COX inhibition