NBME 3 Help

[alternatego]

tried searching for a topic like this but found nothing, so here go my questions.

Section 3
39. 40 yo woman with cholelithiasis, she begins oral therapy with ursodeoxycholic acid. Which is the best rationale for treatment?
A. Addition of bilirubin into the bile
B. Decrease in the concentration of bile acids
C. Decrease in the ratio of cholesterol to bile acids
D. Increase in the ability of the gallbladder to concentrate bile
E. Increase in the concentration of lecithin in the bile

I chose C, answer sheet says it is B, but I don't know what to think about that answer.

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[Myxedema]

You're correct. From Katzung Pharmacology: "...Prolonged ursodiol therapy expands the bile acid pool, this does not appear to be the principal mechanism of action for dissolution of gallstones. Ursodiol decreases the cholesterol content of bile by reducing hepatic cholesterol secretion."

Decreased cholesterol secretion --> Decrease in cholesterol/bile acid ratio

 

[alternatego]

Thanks!

 

[Belleza156]

You're correct. From Katzung Pharmacology: "...Prolonged ursodiol therapy expands the bile acid pool, this does not appear to be the principal mechanism of action for dissolution of gallstones. Ursodiol decreases the cholesterol content of bile by reducing hepatic cholesterol secretion."

Decreased cholesterol secretion --> Decrease in cholesterol/bile acid ratio

Actually he's not correct. The question isn't asking the MOA, its asking why would you give ursodiol to a pt......to dissolve and/or prevent gallstones. It's end effect of changing the ratio isn't what's being tested.

The question is testing to see if you know that ursodiol therapy will solubilize cholesterol and increase the concentration level at which gallstones form (ursodiol will make up more than half of the concentration of the bile; its not that bile will consist of more bile acid....even though more bile will eventually be made).

"The overall effect of ursodiol is to increase the concentration level at which saturation of cholesterol occurs. The various actions of ursodiol combine to change the bile of patients with gallstones from cholesterol-precipitating to cholesterol-solubilizing, thus resulting in bile conducive to cholesterol stone dissolution. "

http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=72736
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[Myxedema]

This is just semantics. The rationale of a treatment is of course on the mechanism of action of a drug (e.g. What is the rationale of using foscarnet in acyclovir-resistant herpes?), just as it's based on the pathophysiology, side effect profile, efficacy, etc. So, the answer to the question "why would I give ursodiol to a patient" is "to reduce the cholesterol secretion in order to decrease the cholesterol/bile acid ratio, which will decrease the likelihood of stone precipitation and formation"

 

[Belleza156]

Answer continues to be B.

You may want to try reading the link I posted, but you will need to read the whole thing, jot just the couple lines that support answer C. BTW answer D is also a MOA of ursodiol

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[Myxedema]

Answer continues to be B.

You may want to try reading the link I posted, but you will need to read the whole thing, jot just the couple lines that support answer C. BTW answer D is also a MOA of ursodiol

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So is this your argument?: There's reduced concentration of bile acids in cholelithiasis --> Ursodiol increases the bile acid concentration --> Decreases the likelihood of precipitation of cholesterol; increases cholesterol solubility in bile

 

[Belleza156]

So is this your argument?: There's reduced concentration of bile acids in cholelithiasis --> Ursodiol increases the bile acid concentration --> Decreases the likelihood of precipitation of cholesterol; increases cholesterol solubility in bile

Not quite. The bile acid is usually made up of hydrophobic bile acids. These are the bile acids that accumulate and cause cholesterol gallstones. Ursodiol which is derived from cholesterol is naturally present in bile acid , but in small quantities and its hydrophillic. So when you pump up the patient with ursodiol you are changing the concentration of the endogenous hydrophobic bile acid, you are decreasing it. Ursodiol will eventually go from being 5 % of bile acid to ~50-60% of bile acid. This makes bile acid more hydrophillic, enough so that cholesterol stones dont form.

The question is poorly phrased, but then again its also from an old NBME, so you wouldn't expect such ambiguity on more recent NBMEs. The answer should be phrased better to say "decreases the hydrophobic bile acid concentration" because in reality you are just adding more bile salt but a hydrophillic one instead. Since you are adding a synthetic bile salt it can be said that you are decreasing the overall concentration.

When I did this question in June I was convinced that every answer key was wrong, and C had to be the answer. But after doing a few questions in Uworld related to the topic I realized it was in fact B.

 

[Myxedema]

Not quite. The bile acid is usually made up of hydrophobic bile acids. These are the bile acids that accumulate and cause cholesterol gallstones. Ursodiol which is derived from cholesterol is naturally present in bile acid , but in small quantities and its hydrophillic. So when you pump up the patient with ursodiol you are changing the concentration of the endogenous hydrophobic bile acid, you are decreasing it. Ursodiol will eventually go from being 5 % of bile acid to ~50-60% of bile acid. This makes bile acid more hydrophillic, enough so that cholesterol stones dont form.

I understand your logic, but this bold part is not the main reason why ursodiol decreases bile stones. It's obviously true, but both pharmacology and medicine texts I've checked list this (expansion of bile acid pool) as a minor mechanism. They list decreased cholesterol excretion as the main reason. So that's why I chose C. But at any rate, I agree with what you've written below:

The question is poorly phrased, but then again its also from an old NBME, so you wouldn't expect such ambiguity on more recent NBMEs. The answer should be phrased better to say "decreases the hydrophobic bile acid concentration" because in reality you are just adding more bile salt but a hydrophillic one instead. Since you are adding a synthetic bile salt it can be said that you are decreasing the overall concentration.

When I did this question in June I was convinced that every answer key was wrong, and C had to be the answer. But after doing a few questions in Uworld related to the topic I realized it was in fact B.

I agree and I thank you for your comment. This was a good question to review the bile acid metabolism.