Which of the following drug causes irreversible inhibitor of cyclooxygenase?
ANSWER: (B) AspirinREF: Goodman an dGillman's 11TH ed, Page 440, KDT 6th edition, Katzung 9th edition http://en.wikipedia.org/ wiki/ Cy clooxy genas eRepeat in December 2010MECHANISM OF ACTION OF ASPIRIN:Non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin and derivatives of ibuprofen, inhibit cyclooxygenase activity of PGH2 Synthase. There are two isoforms of PGH2 Synthase: COX-1 & COX-2 (Cyclooxygenase 1 & 2)Aspirin's ability to suppress the production of prostaglandins and thromboxanes is due to its non-competitive irreversible inactivation of the cyclooxygenase (COX1 & COX2) enzyme.Cyclooxygenase is required for prostaglandin and thromboxane synthesis. Aspirin acts as an acetylating agent where an acetyl group is covalently attached to a serine residue in the active site of the COX enzyme. This makes aspirin different from other NSAIDs (such as diclofenac and ibuprofen), which are competitive reversible inhibitors CYCLOXYGENASE: COX1COX 2ALSO KNOWN ASPGH, synthase 1PGH, synthase 2EXPRESSIONAlways present, in all normal tissuesInducible at the site of inflammation (normally very low levels) plus normally in brain & kidneySTIMULUSHumoral stimulationCytokines, growth factors, tumor promotersINCREASE ON STIMULUS2-4 folds10-20 foldsFUNCTIONHousekeeping; e.g. Gastric cytoprotection, Ductus arteriosus patencyInflammatory
Naproxen
Aspirin
Indomethacin
Acetaminophen
Prostaglandins