Heart Failure Drugs

Question 1

What is the major underlying cause of HF?

Answer 1

Inability of the heart to supply O2 to the tissues

Usually a result of chronic Hypertension

Question 2

HF is usually due to _____ ventricular dysfunction

Answer 2

Left

Can be either HFrEF or HFpEF

Question 3

What is the most common mechanism of death for heart failure patients?

Answer 3

Sudden death due to arrhythmias

30-50% of patients with severe symptoms die within one year

Question 4

How does increased preload aggravate HF?

Answer 4

As preload increases, the increased stretch and contractility increase stroke volume

Question 5

Afterload is determined by…

Answer 5

Arterial resistance, from aortic impedance or vascular resistance

Question 6

What types of drugs affect afterload?

Answer 6

ARTERIODILATOR drugs

Increase peripheral resistance via arterial constriction

Question 7

What drugs can act to increase preload?

Answer 7

VENODILATORS

Question 8

Inherent ability of cardiac muscles to shorten and develop force

Answer 8

Myocardial contractility

Question 9

What drugs can be used to affect contractility?

Answer 9

Beta blockers DECREASE contractility

Inotropic drugs INCREASE contractility

Question 10

Why is controlling HR important in HF?

Answer 10

Determines cardiac output

CO = HR x SV

Question 11

What drugs can be used to affect HR?

Answer 11

Reflex tachycardia occurs with HF as the decreased CO increases baroreflex activation and sympathetic stimulation of the heart

BETA BLOCKERS will reduce cardiac work by slowing the HR

Question 12

** What is the MOA for Digoxin

Answer 12

Inhibition of membrane sodium pump (Na/K ATPase) leads to cardiac effects

Increase intracellular Na
Decreased expulsion of intracellular Ca —> increased intracellular Ca —> increased SR Ca —> increased actin-myosin interaction

POSITIVE INOTROPY

Question 13

In normal hearts, heart rate is reduced or slowed by…

Answer 13

Vagal stimulation due to sensitization of arterial barorecepters, stimulation of central vagal nuclei, or increased SA node sensitivity to ACh

Question 14

In failing hearts, ______ is increased

Answer 14

Cardiac output

Sympathetic tone is already high. As digitalis increases myocardial contractility, the sympathetic tone will be reduced

Question 15

**What are the earliest signs of Digoxin toxicity?

Answer 15

GI - N/V/D even at low dose (disappear after d/c)

Other adverse effects:
Digoxin has narrow margin of safety (toxic even at therapeutic doses)
CNS side effects (HA, fatigue, drowsiness, hallucinations)
ARRHYTHMIAS

Question 16

**What are the most common and dangerous cardiac side effects of Digoxin?

Answer 16

Arrhythmias (sinus bradycardia, ectopic ventricular beats, AV block, BIGEMINY)

Must stop Digoxin and give K+

V fib is the most common cause of death

Perform regular EKGs

Question 17

How to deal with digoxin intoxication

Answer 17

Minor (GI): discontinue or reduce digitalis

Moderate (arrhythmias): oral or IV K+ along with above

Severe (overdose/life-threatening arrhythmias): immunotherapy with Digitalis Immune Fab along with above

Question 18

**What drug enhances Digoxin toxicities?

Answer 18

***Quinidine (displaces digoxin from tissue binding sites)

***Thiazides/Loops —> hypokalemia-induced toxicity

***Beta blockers further decrease SA/AV node activity

***NE-releasing agents sensitize myocardium to digoxin

Question 19

What drugs can reduce digoxin toxicity?

Answer 19

Those that prevent absorption

Cholestyramine
Bran
Activated charcoal
Etc

Question 20

What drugs can decrease the effectiveness of digoxin?

Answer 20

CCBs (reduce contractility)

Question 21

Which Phosphodiesterase Inhibitor is used in late stage HF?

Answer 21

Milrinone - positive inotropic drug that also causes vasodilation

IV only for acute HF (Palliative only) b/c long term use increases mortality

Question 22

Positive inotropic agent used in short-term treatment of severe refractory HF

Answer 22

Dobutamine (Dobutrex)

Selective B1-agonist —> inotropic effect

IV only

Don’t use with beta blockers

Question 23

Dopamine uses:

Low Dose —> _________

Mod Dose —> _________

High Dose —> __________

Answer 23

Low Dose —> D1 receptors in kidney —> renal vasodilation

Mod Dose —> B1 receptors in heart —> inotropic effect

High Dose —> Alpha receptors in vessels —> vasoconstriction

Used for short-term treatment of severe refractory HF (useful if an increased BP is needed)

Question 24

How are diuretics used in HF?

Answer 24

Reduce salt and water retention —> reduced venous pressure, reduced edema, and reduced cardiac size

Spironolactone and eplerenone have additional benefits over other directives by inhibiting aldosterone receptors —> reduced mortality rate

Watch K/Mg while on diurectics

Question 25

What are all the drugs that reduce HF mortality?

Answer 25

Aldosterone antagonists (Spironolactone and eplerenone)

Beta blockers,

ACE/ARBs

ARB + neprilysin inhibitor

Question 26

Backbone of HF treatment

Answer 26

ACE inhibitors

Will diminish cardiac workload by:
• Decreasing afterload through AngII-induced vasoconstriction
• Decreasing preload by reducing aldosterone release

Question 27

Why do you get a dry cough with ACE inhibitors but not ARBs?

Answer 27

Because of the reduction in bradykinin metabolism (also performed by ACE)

Question 28

Sacubitril/Valsartan (Entresto) is a combo of what two drug classes?

Answer 28

ARB (Valsartan)

Neprilysin Inhibitor (Sacubitril) - degrades natriuretic peptides, bradykinin and others

Better at reducing mortality in HF compared to ACEs alone

Question 29

The Neprilysin inhibition in Sacubitril/Valsartan does what?

Answer 29

Decreases:
• Vasoconstriction
• Sodium retention
• Cardiac remodeling

Question 30

***Adverse effects and contraindications of Sacubitril/Valsartan

Answer 30

Hypotension
Hyperkalemia (from the ARB) esp with a K-sparing diuretic
COUGH and ANGIOEDEMA

Contraindicated in 2nd/3rd trimester of pregnancy (teratogenic)
No concurrent use with an ACE

Question 31

Which beta blockers are used to decrease mortality in early HF?

Answer 31

Carvedilol (Coreg)
Metoprolol (Lopressor)

Dangerous in severe, end-stage HF b/c of the NEGATIVE INOTROPIC EFFECT

Question 32

Vasodilators are used in HF to …

Answer 32

Reduce preload, afterload, or both —> reduced damaging remodeling of the heart

Examples:
Sodium nitroprusside (VEINS —> preload)
Isosorbide dinitrate
Hydralazine

Question 33

Which drug blocks the funny current in the heart —> reduced HR

Answer 33

Ivabradine (Corlanor)

Reduces HR when beta blockers cant/wont