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 +0  (nbme22#45)

NBME 20 has a question with a guy taking over the counter cough medication and now he has constipation. Want to guess the answer? It was dextro! -> https://nbmeanswers.com/exam/nbme20/458

So I’m pretty sure the NBME 22 question is just straight up wrong.

rockediny  No, not so. Dextro *is* the correct answer here. From the choices given, dextro is the least likely to cause constipation since its main mechanism of action is NMDA antagonism w/ *some* opioid activity -- it can cause constipation but the other choices are MUCH MORE likely to. As for diphenhydramine = it is not appropriate for elderly patients and it isn’t an antitussive.
surely_not_a_robot_  Agreed with @rockediny. Dextro would be the best to prescribe because it has the least amount of constipation out of the drugs that you could prescribe + Anti-cholinergics in the elderly have much more morbidity and risk of mortality.
keycompany  The only way to wrap your head around this is to conclude that Dextro is the "least wrong". I thought a lot about this, and I can't think of any drugs that can suppress cough without also causing constipation, so it makes sense that Dextro is the answer because it is the "least likely" to cause significant constipation. This is probably just a clinical correlate that will be learned during rotations/years in practice.

 +1  (nbme22#45)

How is a synthetic opioid (dextromethorphan) that you can find with a 2 second google search as causing constipation the correct answer? Is it just because tiotropium wouldn’t treat the cough?

moneysacs  Tiotropium would cause constipation bc it’s an anticholinergic. Don’t have any insight into why dextromethorphan is the right answer though, other than process of elimination and diphenhydramine wouldn’t treat his symptoms.
upstairs_bumblebee  I thought it was dextromethorphan because it would bind NMDA receptors and have weaker opioid effect = less constipation? Idk though :/
dr_salface  I agree. I mainly went by way of elimination but even DXM made me think of opiod-induced constipation. Though, all the other answer choices had obvious anticholinergic effects. At least, that was my reasoning for picking dxm.

 +6  (nbme21#4)

Ubiquitin-mediated proteolysis is not reversibly affected by insulin. The question asks for reversible ways that insulin affects it, and ubiquitination would lead to degradation via proteases, which is not reversible. Nuclear/cytoplasmic shunting makes sense because FOXO is a transcription factor, so it can’t do its job if it is in the cytoplasm!

meningitis  Thank you for your explanation! One question: How about the serine phosphorylation? Is it answered by pure memorization that the FOXO TF is serine phosphorylated, or is it a general fact that all TF's are serine-threonine phosphorylated?
tsl19  I'm not sure, but it may be as simple as this: ubiquitin-mediated proteolysis is irreversible, but both N/C shuttling and phosphorylation are generally reversible processes.
didelphus  I also guessed that FOXO must be a part of the PI3K pathway, since insulin regulates metabolism through PI3K and the question stem specifically mentions that. Phosphorylation is a major part of that pathway, so even indirectly phosphorylation would regulate FOXO. Frustrating question.
niboonsh  yes, FOXO is affected downstream of the activation of PI3K. This is a really good video that explains the whole cascade https://www.youtube.com/watch?v=ewgLd9N3s-4
alexb  According to wikipedia (https://en.wikipedia.org/wiki/FOXO1) phosphorylation of FOXO1 is irreversible. This is referring to phosphorylation of serine residues on FOXO by Akt, which occurs in response to insulin. But the NBME answer suggests it's reversible. What's up?

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