Regarding Dapsone...Excretion and MOA

shevyatiwari's version from 2015-10-26 10:01

Section 1

Question Answer
Biliary excretion F. Dapsone and metabolites conjugated in liver as dapsone glucaronide - more water soluble and renally excreted
Glucaronide metabolites are major metabolies and easily found in urine and circulation F Found in urine but NOT easily detected in circulation due to rapid clearance
No significant enterohepatic circulationF. Significant as activated charcoal increases elimiation up to 5 times
Excreted unchanged via kidneyF. Renally excreted with parent drug, N-hydrocydapsone are main products - most oftern conjugated with glucaronide
Probenecid reduces renal clearanceT. implies renal tubular transport
Dose adjustment required for liver failure and cirrhosis F. No effect
Half life requred BD dosing F. Half life 24-26hrs permits daily dosing

Section 2

Question Answer
Inhibition of folic acid pathway is MOA for inflammatory diseasesF. MOA of folic acid pathway relevant only for leprosy. For inflammation MOA - UNKNOWN
Most useful for treating disease with eosinophilic infiltrates in the skinF. NEUTROPHILIC INFILTRATES
May directly affect neutrophilic functionT.
Inhibits neutrophil myeloperoxidaseT
Inhibits neutrophil respiratory burst mechanisms and inhibits neutrophil tissue damageT
Induction of esoinophil myeloperoxidaseF Inhibits eosinophil myleoperoxidase ( enxyme also present in monocytes
Inhibition of neutrophil adhesion to vascular endothelium integrinsTrue
Inhibits chemotaxis in part by inhibition of f-met-leu-phe mediated chemotaxisTrue
Inhibitis dihydropteroate synthetase (enzyme in reduction of folic acid)T .MOA = leprosy
Inhibits generation of 5-lipogenase products in neutrophils and macrophagesTrue
Dapsone inhibits myelpperoxidase and reduces oxidative damage to normal tissues in neutrophilic and granulomatous dermatosesTrue
Dapsone can be metabolised by N-acteyltransferase which is generally decreased in slow acetylatorsT
Increase in adverse effects assoc. with Dapsone seen in slow acetylatorsFalse
Dapsone can be metabolized by N-hydroxylase leading to less reactive metabolite dapsone hydroxylamineF. to MORE REACTIVE metabolite dapsone hydroxylamine
Glucaronidation of monoacetyl dapsone leads to water soluble metabolites and renal excretionTrue
G6PD is an antioxidant emzyme with a net effect of increased hydroxylamine metabolites which are strong antioxidantsF G6PD is an antioxidant enzyme with net result of DECREASED hyroxylamine which are strong OXIDANTS
Genetic deficiency of G6PD - resultant increase in haemolysis as hydroxylamine metabolites act as strong oxidants (RBC membrane damage )True

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