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NBME 22 Answers

nbme22/Block 1/Question#4
A 48-year-old man begins furosemide therapy ...
Decreases the luminal permeability to Na+ in the collecting duct🔍

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 +4  upvote downvote
submitted by hello(184),

Spironolactone and eplerenone are potassium-sparing diurectics that inhibit the Na/K ATPase. Na/K ATPase is on the basolateral membrane. None of the answer choices fit with this.

Amiloride and triamterene are also potassium-sparing diuretics. The mechanism is to block ENaC channels on the luminal membrane, this is choice "B."




Should use a potassium-sparing diuretic (FA 591). Triamterene and amiloride work by blocking ENaC channels.




I got that it needed to be a potassium sparing diuretic. Is there a reason it cannot be an aldosterone antagonist? I chose blocks basolateral K+ channels as these decrease the basolateral K+/Na+/ATPase because the wording of the correct answer did not make sense to me -- assuming they were going for an ENaC blocker (and that decreased luminal permeability indicates that Na+ would be remaining in the lumen, not remaining in the principal cell as I originally thought).

luckeroo  I think the reason it’s a potassium-sparing diuretic rather than an aldosterone antagonist has less to do with why the aldosterone antagonist cannot be used and more to do with the fact that a potassium-sparing diuretic would be more of a “first-line” adjunctive diuretic treatment. +1  
luckeroo  As for the answer choice, potassium sparing diuretics achieve their overall anti-aldosterone effect by competitively inhibiting aldosterone receptors on the interstitial side (decreasing the Na/K-ATPase effect of shunting Na into the blood), thereby decreasing the gradient for sodium to enter the cell from the luminal aspect, blocking ENaC. +2  
yotsubato  There is no such thing as "Basolateral K Channel" there is only basolateral Sodium Potassium Pumps which are controlled by aldosterone. FA pg 573 +9  
nwinkelmann  @yotsubato LOL.... why didn't I think of it that what?! (by the way, that LOL is for me). The only basolateral K channel is the nephron (based on the first aid picture) is in the thick ascending limb of the loop of henle. +  
hello  Spironolactone and eplerenone are potassium-sparing diurectics that inhibit the Na/K ATPase, so I'm not sure what @luckeroo is referring to. Spironolactone and aplerenone are both ALDO antagonists. Na/K ATPase is found on the basolateral membrane. None of the answer choices fit with this. Amiloride and triamterene are also potassium-sparing diuretics; their mechanism is to block ENaC channels on the luminal membrane, this is choice "B." +1  
rxfit  From Katzung Board Review: "Spironolactone and eplerenone are steroid derivatives and act as pharmacologic antagonists of aldosterone in the collecting tubules. By combining with and blocking the intracellular aldosterone receptor, these drugs reduce the expression of genes that code for the epithelial sodium ion channel (ENaC) and Na+/K+ ATPase. Amiloride and triamterene act by blocking the ENaC sodium channels (Figure 15–5). (These drugs do not block INa channels in excitable membranes.) Spironolactone and eplerenone have slow onsets and offsets of action (24–72 h). Amiloride and triamterene have durations of action of 12–24 h." So both K-sparing subtypes are technically correct. +  



It doesn't matter which potassium-sparing diuretic you use. You can still get to this answer. Aldosterone normally upregulates Na/K ATPase in the principal cells of the CD, decreased Na+ intracellularly, which leads to increased ENaC activity. Spironolactone/eplerenone will inhibit this upregulation of ENaC, leading to decreased permeability to Na+ in the CD.

Obv amiloride and triamterene will block principal cell ENaC. It's all in the same class so they will all lead to this effect :)

FA 2019 pg 573




 +0  upvote downvote
submitted by j000(-2),

spironolactone and eplerenone are aldosterone receptor antagonist (they block the effect of aldosterone by blocking the basolateral Na/K ATPase pump), this is not the same thing as blocking a basolateral K+ channel. They block and decrease the potassium conduction. There is no basolateral K+ channel

if the (A) were to say "decrease K+ conduction in collecting duct" that might be correct

so (B) is correct. Triamteren and amiloride block Na+ channel on apical (luminal side) side, decrease permeability of Na+




 +0  upvote downvote
submitted by usmle11a(44),

spironolactone acts as an aldosterone antagonist which means decreasing Na+ permeability

j000  i think they're referring to triamterene and amiloride, not spironolactone spironolactone doesn't actually decrease Na+ permeability +  
jackie_chan  @j000 It doesnt matter, spiro and triamterene/amiloride have a common effect of messing with ENaC. Aldosterone upregulates ENaC, spiro would inhibit that so in effect would decrease luminal permeability to Na in duct due to fewer ENaC channels; triamterene would block the channel directly, same effect. http://tmedweb.tulane.edu/pharmwiki/doku.php/potassium_sparing_diuretics +  



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