Heart Failure Drugs Flashcards
What is the major underlying cause of HF?
Inability of the heart to supply O2 to the tissues
Usually a result of chronic Hypertension
HF is usually due to _____ ventricular dysfunction
Left
Can be either HFrEF or HFpEF
What is the most common mechanism of death for heart failure patients?
Sudden death due to arrhythmias
30-50% of patients with severe symptoms die within one year
How does increased preload aggravate HF?
As preload increases, the increased stretch and contractility increase stroke volume
Afterload is determined by…
Arterial resistance, from aortic impedance or vascular resistance
What types of drugs affect afterload?
ARTERIODILATOR drugs
Increase peripheral resistance via arterial constriction
What drugs can act to increase preload?
VENODILATORS
Inherent ability of cardiac muscles to shorten and develop force
Myocardial contractility
What drugs can be used to affect contractility?
Beta blockers DECREASE contractility
Inotropic drugs INCREASE contractility
Why is controlling HR important in HF?
Determines cardiac output
CO = HR x SV
What drugs can be used to affect HR?
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
** What is the MOA for Digoxin
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
In normal hearts, heart rate is reduced or slowed by…
Vagal stimulation due to sensitization of arterial barorecepters, stimulation of central vagal nuclei, or increased SA node sensitivity to ACh
In failing hearts, ______ is increased
Cardiac output
Sympathetic tone is already high. As digitalis increases myocardial contractility, the sympathetic tone will be reduced
**What are the earliest signs of Digoxin toxicity?
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
**What are the most common and dangerous cardiac side effects of Digoxin?
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
How to deal with digoxin intoxication
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
**What drug enhances Digoxin toxicities?
***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
What drugs can reduce digoxin toxicity?
Those that prevent absorption
Cholestyramine
Bran
Activated charcoal
Etc
What drugs can decrease the effectiveness of digoxin?
CCBs (reduce contractility)
Which Phosphodiesterase Inhibitor is used in late stage HF?
Milrinone - positive inotropic drug that also causes vasodilation
IV only for acute HF (Palliative only) b/c long term use increases mortality
Positive inotropic agent used in short-term treatment of severe refractory HF
Dobutamine (Dobutrex)
Selective B1-agonist —> inotropic effect
IV only
Don’t use with beta blockers
Dopamine uses:
Low Dose —> _________
Mod Dose —> _________
High Dose —> __________
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)
How are diuretics used in HF?
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
What are all the drugs that reduce HF mortality?
Aldosterone antagonists (Spironolactone and eplerenone)
Beta blockers,
ACE/ARBs
ARB + neprilysin inhibitor
Backbone of HF treatment
ACE inhibitors
Will diminish cardiac workload by:
• Decreasing afterload through AngII-induced vasoconstriction
• Decreasing preload by reducing aldosterone release
Why do you get a dry cough with ACE inhibitors but not ARBs?
Because of the reduction in bradykinin metabolism (also performed by ACE)
Sacubitril/Valsartan (Entresto) is a combo of what two drug classes?
ARB (Valsartan)
Neprilysin Inhibitor (Sacubitril) - degrades natriuretic peptides, bradykinin and others
Better at reducing mortality in HF compared to ACEs alone
The Neprilysin inhibition in Sacubitril/Valsartan does what?
Decreases:
• Vasoconstriction
• Sodium retention
• Cardiac remodeling
***Adverse effects and contraindications of Sacubitril/Valsartan
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
Which beta blockers are used to decrease mortality in early HF?
Carvedilol (Coreg)
Metoprolol (Lopressor)
Dangerous in severe, end-stage HF b/c of the NEGATIVE INOTROPIC EFFECT
Vasodilators are used in HF to …
Reduce preload, afterload, or both —> reduced damaging remodeling of the heart
Examples:
Sodium nitroprusside (VEINS —> preload)
Isosorbide dinitrate
Hydralazine
Which drug blocks the funny current in the heart —> reduced HR
Ivabradine (Corlanor)
Reduces HR when beta blockers cant/wont
