Drugs for CHF

Question 1

If you’re Stage A for CHF what does that mean and what measures do you take to prevent it?

Answer 1

You’re AT RISK.

Lifestyle changes: Manage HTN, lipids, diabetes. No smoking or alcohol.

Preventative Drugs: ACE inhibitors (Captopril… any pril)

Question 2

Stage B CHF means what? What drug class do you add to your ACE inhibitor at this point?

Answer 2

Stabe B CHF means your EF has dropped below 50%

Keep taking your ACE inhibitor, and add a B-blocker to decrease the workload on your heart.

Question 3

Stage C CHF is indicated by what? What do you take now?

Answer 3

Significant onset of symptoms indicates a Stage C CHF patient.

Edema, Dyspnea, Orthopnea, PND.

Take your ACE inhibitor, your B-blocker, and add a diuretic, Digoxin, and Spironolactone.

Question 4

WTF is spironolactone?

Answer 4

A K+ sparing diuretic. (Makes you secrete water but retain your body’s potassium content)

It’s a direct Aldosterone antagonist.

Question 5

What is the treatment when you reach Stage D Heart Failure?

Answer 5

You have refractory edema, symptoms even at rest, and your heart has pretty much had it.

IV inotropes to keep you going till you can get a heart transplant.

Significant mortality risk.

Question 6

WHy are ACE inhibitors indicated LONG before you have any hemodynamic issues (congestion… pump failure) with CHF?

Answer 6

ACE inhibitors prevent and may even reverse the effect of Angiotensin II’s mitogenic effects on the myocardium.

• Cardiac myocyte hypertrophy
• vascular smooth muscle hypertrophy
• Fibrosis of the heart and vessels;remodeling
• Atherosclerosis

SLOWS THIS CRITICAL PROCESS that has to happen for Heart Failure to occur.

Question 7

WHich is better? ACE inhibitors or ARBs?

Answer 7

ACE inhibitors, because they’ve been shown to decrease morbidity and mortality in CHF.

There isn’t enough data on ARBs yet, so ACE inhibitors are preferred unless the patient can’t stand the cough (bradykinin buildup)

Question 8

Does combining ACEi’s and ARBs have a beneficial effect?

Answer 8

Nope. No increased benefit. Take one or the other.

Question 9

What is the name of the direct Renin inhibitor?

Answer 9

Aliskiren.

the one that ends in “REN” inhibits RENin.

Question 10

Name the most common ACE inhibitors.

Answer 10

Captopril, Lisinopril.

Question 11

Name the most common ARB.

Answer 11

Losartan.

Question 12

What drug is renoprotective in diabetics?

Answer 12

Captopril (or any ACE inhibitor)

Question 13

Side effects of ACE inhibitors.

Answer 13

most common: HYPOTENSION (esp. first dose)
2nd most common: DRY IRRITATING COUGH (bradykinin)

Others:
Na+ depletion (since you’re secreting it in urine)
Hyperkalemia (you retain it)
Andioedema

Question 14

MOA and side effects of Aliskiren.

Answer 14

MOA: Direct inhibitor of Renin’s protease action (no Ang –>Ang1)

Toxicity: like the others…
Hypotension
Hyperkalemia
Andioedema

INHIBITS p-GLYCOPROTEIN, so be careful in use with antibiotics

Question 15

Side effects of ARBS:

Answer 15

Hypotension
Hyperkalemia
Liver Dysfx

Question 16

What B-blocker is approved in the US for HTN but NOT CHF?

Answer 16

Nebivolol (the 3rd generation with NO inducing activity)

BUT Docs use it off-label in the US anyway. It’s approved in Europe. Why not.

Question 17

What are the beneficial effects of B-blockers in CHF?

Answer 17

Prevent B1 receptors from becoming over saturated and less responsive to Epi and NE. If chronically stimulated by Epi and NE, the B-receptors will down regulate and the heart will become less excitable, contributing to the heart failure.

There are 2 mechanisms/pathways of B-receptor activation.

1. Acute stimulation/high receptor levels: leads to increased inotropic effects via increased calcium sensitivity, benefiting the heart. (no gene expression is altered)
2. Chronic stimulation/lower receptor levels: myocyte hypertrophic effects via altered gene expression. (deleterious)

We just want to prevent the second one from happening.

Question 18

What B-blocker is used the most for CHF?

Answer 18

Bisoprolol
Metoprolol
Carvedilol

Question 19

Just a reminder… what are the 3 extra effects of Carvedilol?

Answer 19

Antioxidant activity
A antagonism
Ca2+ blocker

Question 20

MOA of digoxin.

Answer 20

Increases the intracellular Ca2+ concentration by acting on 2 pumps:

Na+/K+ ATPase
Na+/Ca+ exchanger

Increases contractility of myocytes, thereby increasing SV.
(maintains CO)

increases inotropic response to endogenous neurotransmitters.

Question 21

Talk about Digoxin.

Answer 21

Digoxin does 2 relatively contradictory things, and use depends on the situation. For CHF, we use it as a + inotrope.

Digoxin is a cardiac glycoside, and is beneficial because you can measure its serum levels and keep track of its usage (patient-specific)

Question 22

Digoxin is most effective when used in conjunction with….

Answer 22

Vasodilators –> Decrease afterload

Diuretics –> reduce preload by keeping volume down

Question 23

Your patient is starting to see Halos around lights, and feeling confused and tired. What do you need to give him to combat this drug toxicity? What drug is causing it?

Answer 23

Digoxin toxicity.

Give him DIGIBIND

Question 24

Why is it important that the serum level of digoxin can be measured? (one of the only reasons it can even be used…)

Answer 24

Digoxin has a narrow therapeutic window that varies from person to person. Monitoring their response and simultaneous serum levels is the only way to safely treat a patient.

Question 25

Does Digoxin use significantly lower morbidity and mortality in CHF patients?

Answer 25

YEP

Question 26

What’s the EF threshold for Digoxin administration?

Answer 26

Use Digoxin when the EF < 25.

Question 27

Name the most commonly used Loop Diuretic.

Answer 27

Furosemide

Question 28

Name the 2 K+ sparing diuretics that are direct Aldosterone Inhibitors.

Answer 28

Spironolactone and Eplerenone

Question 29

Main side effect of diuretics?

Answer 29

Electrolyte imbalance
Hypokalemia (except with spironolactone and eplerenone), Hyponatremia
Hypotension

Question 30

Which of the diuretics improves survival and prognosis of a CHF patient?

Why?

Answer 30

Spironolactone and Eplerenone (the K+ sparing direct aldosterone inhibitors)

Why? Aldosterone has a mitogenic effect on the myocardium. (same reason ACE inhibitors improve morbidity/mortality….block the cause of cell growth)

Loop diuretics like Furosemide and Bumetide have no effect on morbidity/mortality.

Question 31

How do vasodilators help in CHF?

Answer 31

Vasodilators cause decreased TPR, which lowers the BP, and decreases after load.

Question 32

Name the main vasodilator drug.

Answer 32

HYDRALAZINE …. used only for patients who can’t tolerate ACE inhibitors.

NESIRITIDE –> human recombinant BNP
- naturally combats renin and aldosterone release

Question 33

What effects does Nesiritide have on preload and after load?

Answer 33

LOWERS BOTH

Question 34

What drugs are used to manage advanced CHF?

Answer 34

IV vasodilators : Nitrates , or Nesiritide for those who can’t tolerate nitrates.

IV inotropes: Dobutamine for a bit till you can get patient on Digoxin long term

TRANSPLANT

Question 35

MOA of Dobutamine

Answer 35

B-agonist –> Works in absence of endogenous NTs

Only use as a transition drug