4.4 - Heart Failure Drugs

Question 1

What is systolic heart failure? What causes it?

Answer 1

HF explained by decreased effectiveness of ventricles
Causes include:
–> Cardiomyopathies
–> MI
–> HTN
–> Valvular disease

Question 2

What are signs of HF?

Answer 2

Activation of SNS and RAAS
–> Increased contractility, tachycardia, HTN (compensatory mechanisms)
–> Increase in preload and afterload
–> Decreased tissue perfusion
–> Edema
–> Diaphoresis

Question 3

Cardiac output =

Answer 3

Heart Rate x Stroke Volume

Question 4

What causes an increase in preload in HF?

Answer 4

Fluid buildup behind the heart increases EDV –> Increases pressure on heart during diastole

Question 5

What causes increase in afterload in HF?

Answer 5

RAAS causes vasoconstriction, which puts more pressure on the heart during systole.

Question 6

What kinds of drugs are used to treat chronic HF?

Answer 6

ACE inhibitors or ARBs
–> Reduce preload + afterload

B-Blockers
–> Protect heart from deleterious effects of SNS overstimulation

Diuretics (K-sparing/loop)
–> Reduce pulmonary or peripheral edema

Nitroglycerin + hydralazine
–> Reduce preload + afterload

Question 7

What would you give to someone to treat HF who does not tolerate ACEi/ARB/ARNI?

Answer 7

Hydralazine + nitrate

Question 8

Can digoxin be used for acute or chronic HF treatment?

Answer 8

Chronic patients that also have a-fib

Question 9

What are BNP natriuretic peptides?

Answer 9

A substance released by the heart and other tissues when blood volume is too high

Question 10

What is neprilysin?

Answer 10

A substance that breaks down natriuretic peptide and AngII

Question 11

What is sacubitril? What are precautions to using it?

Answer 11

Angiotensin Receptor Neprisyl Inhibitor (ARNI)
–> Inhibits neprilysin, an enzyme that breaks down BNP natriuretic peptides, which are released when blood volume is too high

Question 12

What is ivabradine?

Answer 12

Blocks ion channel responsible for generating SA node pacemaker current –> slows accelerated HR (>70)

Question 13

What kinds of drugs are dapaglifozin, empaglifozin, and canaglifozin?

Answer 13

SGLT-2 Inhibitors
–> Inhibit Na/glucose reabsoption in proximal tubule, diuretic effects, reduces preload

Question 14

What are the adverse effects of SGLT-2 Inhibitors?

Answer 14

Causes urine high in glucose
–> fungal infections
–> polyuria
–> hypotension
–> Euglycemic diabetic ketoacidosis

Question 15

What kind of drug is digoxin?

Answer 15

A cardiac glycoside

Question 16

What plant are cardiac glycosides from?

Answer 16

Digitalis

Question 17

How do cardiac glycosides work? (mechanism of action)

Answer 17

Blocks Na-K ATPase
–> Competes with potassium, so if someone is hyperkalemic it will increase the effects of the drug
–> Results in increased intracellular Ca levels

Results in increased force of contraction. Electrical effects include decreased HR and atrioventricular conduction

Question 18

What are the adverse effects of cardiac glycosides?

Answer 18

–>N&V
–> Arrythmias (late afterdepolarization)
–> Seeing concentric circles around light
–> Narrow therapeutic index - be aware of K levels

Question 19

How do you treat a cardiac glycoside overdose?

Answer 19

Neutralizing anti-digoxin antibody fragments (Digiband)

Question 20

What is a late/delayed afterdepolarization?

Answer 20

unwanted depolarization after the action potential

Question 21

What drug causes delayed/late afterdepolarization?

Answer 21

Digoxin

Question 22

What kinds of drugs cause early afterdepolarization?

Answer 22

Class III antiarrhythmic drugs
–> Sotalol
–> Amiodarone

Question 23

How do we treat acute HF?

Answer 23

Increase O2 sats (>92%)
–> Intubation, O2

Reduce volume overload
–> i.v. furosemide

Increase cardiac contractility and BP
–> Dobutamine, dopamine, milrinone

Question 24

At high doses, what does dopamine do?

Answer 24

Stimulate a1 - vasoconstriction

Question 25

How does cAMP effect the heart vs vascular smooth muscle?

Answer 25

In smooth muscle
–> Relaxation of BVs

In the heart
–> Increased force of contraction

this is good for treating HF!

Question 26

Which enzyme degraded cAMP?

Answer 26

Phosphodiesterase

Question 27

Which drugs are phosphodiesterase inhibitors?

Answer 27

Milrinone and Inamrinone

Question 28

Why is the use of phosphodiesterase inhibitors limited?

Answer 28

They have numerous adverse effects and linked to non-specificity
–> e.g., also increases cGMP, which is the mechanisms of action of eretile dysfunction drugs