Kaplan Pharm Question

[MudPhud20XX]

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In the treatment of congestive heart failure, which drug provides the benefits of lowering preload, lowering afterload, and inhibiting cardiac remodeling?

A. Digoxin
B. Furosemide
C. Inamrinone
D. Lisinopril
E. Spironolactone

I chose E, but the answer is D. Why not E?

I thought spironolactone inhibits cardiac remodeling? Is it b/c it has nothing to do with lowering afterload and preload?

Also, when it says it reduces cardiac remodeling, what is the mechanism? How does the drug inhibit the cardiac remodeling?

Many thanks in advance.

 

[shigella123]

After doing UW I would have gone for E too. What does the explanation say?

 

[MudPhud20XX]

Wow you are not sleeping? Thanks for the feedback.

Here is the explanation:

ACE inhibitors such as lisinopril are considered drugs of choice for the chronic management of heart failure. These drugs provide many benefits, including lowering both preload and afterload, inhibiting cardiac remodeling, and prolonging survival. Spironolactone can also inhibit remodeling and prolong survival but doesn't have any effect on afterload. (and preload too.) Furosemide lowers preload as its primary benefit in heart failure.

 

[shigella123]

Nope, not sleeping.

As I remember from UW, spironolactone inhibits aldosterone effects on cardiac fibroblasts and so stops remodeling. But since they are talking about afterload and preload then that's the reason the answer is ACEI.

Thanks for the q, it cleared up my confusion too. 🙂

 

[shigella123]

I'm still confused about when to use carvedilol/spironolactone/ACEI to inhibit CHF remodeling. Which do we use and when?
I knew about the carvedilol and spironolactone from UW, but I had no idea ACEI also stopped remodeling.

 

[Renaissance Man]

That was a tough question. My gut would've chosen E as well, but I don't think diuretics really have an affect on afterload (as you mentioned). These are the types of questions I miss fairly regularly on practice questions. Thanks for sharing as I am not doing Kaplan!

 

[periaqueductal]

In the treatment of congestive heart failure, which drug provides the benefits of lowering preload, lowering afterload, and inhibiting cardiac remodeling?

A. Digoxin
B. Furosemide
C. Inamrinone
D. Lisinopril
E. Spironolactone

I chose E, but the answer is D. Why not E?

I thought spironolactone inhibits cardiac remodeling? Is it b/c it has nothing to do with lowering afterload and preload?

Also, when it says it reduces cardiac remodeling, what is the mechanism? How does the drug inhibit the cardiac remodeling?

Many thanks in advance.

This is a good question and important to understand for renal.
You did the right thing in narrowing it down to D and E based on cardiac remodeling. Both inhibit water retention and therefore decrease preload. The key is reducing afterload. ACEIs prevent conversion of AngI to AngII. AngII is a vasoconstrictor that will increase TPR and thus afterload. Spironolactone is only blocking the effects of Aldo at the DCT. This will not have as direct of an effect on Afterload. So E is the best answer.

 

[alicealicealice]

As for your question on when to use (details not relevant for Step 1 but general knowledge is), ACEi are used for all stages of heart failure (lisinopril 5mg is often the first drug given and then titrated up, with beta blockers then added). Classically, spironolactone has only been shown to have a mortality benefit in NYHA Class 3/4 (RALES Trial).

As for your question on remodeling, a simplified way to look at it:
Remodeling= Structural, functional, and molecular changes of myocytes and surrounding collagen matrix

Main Components of remodeling = Neurohormonal and Hemodynamic stresses

Neurohormonal Remodeling:
Low Cardiac Output-->Body perceives low flow state, thinks you are hypovolemic (even though you may be volume overloaded)-->Release of "hypovolemic hormones" = ADH, Renin, Norepinephrine (Renin in turn causes increase ATII and Aldoserone)--> Exact mechanism is unclear, but suffice it to say that these hormones have direct effect on the structure of the heart with the end result being hypertrophy and fibrosis (evidence: AT and Aldo receptors are found on fibroblasts cultured from myocardial scar tissue, KO AT Receptor mice dont develop heart failure after MI, ACEi and ARB has been shown to reverse remodeling, etc ). High NorE levels are a poor prognostic sign; high catecholamine levels damage the heart directly (in addition to the hemodynamic stresses from elevated BP etc).

So pharmacology is focused on blocking NorE with BetaBlockers, ATII with ACEi/ARBs, and aldo with spironolactone/eplerenone. All 3 groups have been shown to decrease mortality in HF.

Side notes:
Furosemide, hydralazine/nitrates, digoxin have symptomatic benefits (wtih dig reducing hospitalizations) but no proven mortality benefits.

Notable drugs to avoid in HF include calcium channel blockers and NSAIDs (among many others).

 

[ketosisevangelist]

OLD SCHOOL TERM FOR THIS IS BALANCED DILATION!

REMEMBER, ACE INHIBITORS DO THIS....SO DO THE NITRATES (just like the wonderful explanation above me is explaining in beautiful detail)!!!!