Was USMLE Rx wrong with this question?

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Phloston

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I just encountered this question in USMLE Rx:

A patient with a known allergy to sulfa drugs presents to the emergency department with severe shortness of breath and rapid, shallow breathing. A pulmonary examination reveals bilateral crackles halfway up from the bases, and x-ray film of the chest shows pulmonary vascular redistribution and bilateral interstitial markings. The attending physician chooses to treat the patient with a high dose of a diuretic agent. Subsequently, the patient develops muscle weakness and difficulty hearing his wife's voice.

Which of the following diuretics did the physician most likely administer?

A) Acetazolamide

B) Ethacrynic acid

C) Furosemide

D) Hydrochlorothiazide

E) Spironolactone


--------

When I read this question, I thought it was obvious that because the patient has a sulfa allergy, that ethacrynic acid would be the appropriate diuretic to use. Not hard.

However, notice that after the physician administers the diuretic, the patient develops ototoxic effects.

My assumption was that the physician must have administered furosemide instead of ethacrynic acid, because if he had correctly administered the latter, then the ototoxic effects, and patient's condition as a whole, would not have been exacerbated!

Furthermore, USMLE Rx says the answer is ethacrynic acid, not furosemide. Their reasoning is that because the patient has a sulfa allergy, furosemide is not the correct drug to use. Once again, this was never debated, but the vignette suggests the physician unknowingly administered furosemide, thereby causing the patient more harm.

Am I missing something, or is this question just not written well?

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Well, I think your original reasoning was correct in assuming the doc knew what he was doing regarding a sulfa allergy... and loop diuretics can cause ototoxicity (including the non-sulfa ethacrynic acid).. therefore ethacrynic acid should be the clear choice

In regard to muscle weakness, unsure but according to wikipedia... "Etacrynic acid can also cause low potassium levels, which may manifest as muscle cramps or weakness."

Maybe poorly written, but I guess they are emphasizing the potential side effects of loop diuretics overall?
 
Yeah, I don't think his condition was exacerbated. The ototoxicity is a different condition... he's not having a hypersensitivity reaction. If he had a sulfa drug allergy, he'd have a much more severe reaction to furosemide/acetazolamide/HCTZ... so it's reasonable that he's just developing ototoxicity in response to ethacrynic acid, since spironolactone doesn't cause those effects. The muscle weakness is a nonspecific enough sign so that I'd probably just ignore it.
 
I would just think that the ototoxicity is much more salient an outcome of furosemide- vs ethacrynic acid-use. I've always heard that the biggest problem associated with ethacrynic acid is acute gout (i.e. hyperuricaemia). Nevertheless, PubMed does cite ototoxicity as a possible effect of ethacrynic acid.

Borderline question in terms of how it's worded.

It requires being committed to ethracrynic acid causing ototoxicity, as opposed to just acute gout, even though the latter is much more prevalent (it also requires that we believe the doctor was a competent one).
 
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Well, ototoxicity may be an uncommon effect of ethacrynic acid, but it does happen. Just because gout is more common doesn't mean that it'll happen to everybody.

And I don't think we have to rely on the competence of this particular doctor. If the patient was on furosemide, he would have had a sulfa drug allergy.
 
Well, ototoxicity may be an uncommon effect of ethacrynic acid, but it does happen...

Yes, this particular question focused on a less prevalent side-effect. It's good to now know that it could show up.

And I don't think we have to rely on the competence of this particular doctor. If the patient was on furosemide, he would have had a sulfa drug allergy.

We can't rule out sulfa allergy from this vignette alone. His absence of classic SJS doesn't mean we could exclude progressive leukopenia, for instance. After all, acute gout should have been classic for ethacrynic acid.
 
We can't rule out sulfa allergy from this vignette alone. His absence of classic SJS doesn't mean we could exclude progressive leukopenia, for instance. After all, acute gout should have been classic for ethacrynic acid.

Sure, but patients with sulfa allergy will generally have about the same reactions every time you give them a sulfa drug. Of course, that's not always the case, but it's reasonable to expect that.

Also, FA says that ethacrynic acid toxicity is generally "similar to furosemide" except for the fact that it's less likely to cause allergy and less likely to cause gout. So, although ototoxicity may not be common in the real world, it seems like FA (and, consequently, USMLERx) is suggesting that you should consider the side effect profile to be the same as furosemide. So maybe you could consider that to be an oversight (although I wouldn't call it a "mistake" per se) in both USMLERx and FA. Send it in and you might get a $20 gift card out of it.
 
This was actually a great question because it forces one to really contrast furosemide and ethacrynic acid. The issue coming from me is that Rx had barely explained anything. I don't think it would have killed for them to have spent another 60 seconds reinforcing their explanations, but yet again, now that I'm almost finished with the QBank, I'm used to it at this point.
 
Yes, this particular question focused on a less prevalent side-effect. It's good to now know that it could show up.



We can't rule out sulfa allergy from this vignette alone. His absence of classic SJS doesn't mean we could exclude progressive leukopenia, for instance. After all, acute gout should have been classic for ethacrynic acid.

I think its interesting that you say this is a less prevalent side-effect. If I recall correctly, Kaplan stated that Ethacrynic acid has the most prominent side effect of having the worst ototoxicity out of the loop diuretics.

You're doing well though my friend; your reasoning is great :)
 
That's actually a pretty good question. If I remember correctly from pharmacology during our CV block, ethacrynic acid has similar ability to cause ototoxicity, if not more (our professor seemed to emphasize this fact).

This question requires that you ask yourself two questions, and then choose which is most likely:
1) This attending physician did not properly manage this patient and administered furosemide with the full knowledge that the patient had a sulfa allergy. The patient developed ototoxicity as a result.
2) The attending physician properly managed the patient by administering ethacrynic acid due to the patient's sulfa allergy. The patient subsequently developed ototoxicity due to the similar side effect profiles (thus requiring that you remember that EA can cause ototoxicity as well).
 
Kaplan stated that Ethacrynic acid has the most prominent side effect of having the worst ototoxicity out of the loop diuretics.

I'm not at Kaplan QBank yet, but I'll be there soon.

If I remember correctly from pharmacology during our CV block, ethacrynic acid has similar ability to cause ototoxicity, if not more (our professor seemed to emphasize this fact).

Interesting. That's good to know.

----

Well now I'm more aware at this point. Thanks for the help, guys.
 
Yeah, I remember this question, tripped me up too. I think it's poorly worded. I assumed the physician gave the patient furosemide and the patient subsequently developed a reaction to it. I hadn't thought of the fact that the physician already knew about the contraindication of furosemide in this case, and thus gave the patient ethacrynic acid. And both these drugs can cause ototoxic effects.
 
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