[mtoi]

A 26yo woman in her third trimester of pregnancy is mistakenly prescribed sulfametoxazole for uti. Sulfamethoxazole is contraindicated in pregnancy because sulfamethoxazole binds to albumin and can thus displace an important heme degradation product leading tocerebral toxicity in the fetus. The unbound plasma concentration of which of the following intermediate of heme degradation would be affected by sulfamethoxazole administration?
A bilirubin
B bilirubin glucuronide
C biliverdin
D heme
E urobilin
F urobilinogen

 

[lazmo2002]

answer is :
A

 

[Pixie]

A bilirubin

 

[mtoi]

The correct answer is A. heme is degraded peripherally by phagocytic cells into biliverdin by heme oxygenase and then into bilirubin by biliverdin reductase. Bilirubin is then carried by albumin to the liver, where bilirubin is further processed by uridine diphosphate glucuronosyltransferase into bilirubin glucuronide. Bilirubin glucuronide (conjugated direct bilirubin) is much more water-soluble and is then excreted into the colon. Finally, the bacteria in colon deconjugate bilirubin glucuronide to generate urobilinogen, which is excreted in feces; a small fraction of urobilinogen is reabsorbed and excreted as urobilin in urine. Several medications, including sulfonamide antibiotics (such as sulfamethoxazole), warfarin and cholecystographic contrast media bind to albumin at the same site as bilirubin and can thus displace bilirubin from albumin. Unbound bilirubin can deposit in the tissues and is potential neurotoxin to newborns causing acute bilirubin encephalopathy or the chronic permanent sequelae, kernicterus.

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