4.4 - Heart Failure Drugs Flashcards
What is systolic heart failure? What causes it?
HF explained by decreased effectiveness of ventricles
Causes include:
–> Cardiomyopathies
–> MI
–> HTN
–> Valvular disease
What are signs of HF?
Activation of SNS and RAAS
–> Increased contractility, tachycardia, HTN (compensatory mechanisms)
–> Increase in preload and afterload
–> Decreased tissue perfusion
–> Edema
–> Diaphoresis
Cardiac output =
Heart Rate x Stroke Volume
What causes an increase in preload in HF?
Fluid buildup behind the heart increases EDV –> Increases pressure on heart during diastole
What causes increase in afterload in HF?
RAAS causes vasoconstriction, which puts more pressure on the heart during systole.
What kinds of drugs are used to treat chronic HF?
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
What would you give to someone to treat HF who does not tolerate ACEi/ARB/ARNI?
Hydralazine + nitrate
Can digoxin be used for acute or chronic HF treatment?
Chronic patients that also have a-fib
What are BNP natriuretic peptides?
A substance released by the heart and other tissues when blood volume is too high
What is neprilysin?
A substance that breaks down natriuretic peptide and AngII
What is sacubitril? What are precautions to using it?
Angiotensin Receptor Neprisyl Inhibitor (ARNI)
–> Inhibits neprilysin, an enzyme that breaks down BNP natriuretic peptides, which are released when blood volume is too high
What is ivabradine?
Blocks ion channel responsible for generating SA node pacemaker current –> slows accelerated HR (>70)
What kinds of drugs are dapaglifozin, empaglifozin, and canaglifozin?
SGLT-2 Inhibitors
–> Inhibit Na/glucose reabsoption in proximal tubule, diuretic effects, reduces preload
What are the adverse effects of SGLT-2 Inhibitors?
Causes urine high in glucose
–> fungal infections
–> polyuria
–> hypotension
–> Euglycemic diabetic ketoacidosis
What kind of drug is digoxin?
A cardiac glycoside
What plant are cardiac glycosides from?
Digitalis
How do cardiac glycosides work? (mechanism of action)
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
What are the adverse effects of cardiac glycosides?
–>N&V
–> Arrythmias (late afterdepolarization)
–> Seeing concentric circles around light
–> Narrow therapeutic index - be aware of K levels
How do you treat a cardiac glycoside overdose?
Neutralizing anti-digoxin antibody fragments (Digiband)
What is a late/delayed afterdepolarization?
unwanted depolarization after the action potential
What drug causes delayed/late afterdepolarization?
Digoxin
What kinds of drugs cause early afterdepolarization?
Class III antiarrhythmic drugs
–> Sotalol
–> Amiodarone
How do we treat acute HF?
Increase O2 sats (>92%)
–> Intubation, O2
Reduce volume overload
–> i.v. furosemide
Increase cardiac contractility and BP
–> Dobutamine, dopamine, milrinone
At high doses, what does dopamine do?
Stimulate a1 - vasoconstriction
How does cAMP effect the heart vs vascular smooth muscle?
In smooth muscle
–> Relaxation of BVs
In the heart
–> Increased force of contraction
this is good for treating HF!
Which enzyme degraded cAMP?
Phosphodiesterase
Which drugs are phosphodiesterase inhibitors?
Milrinone and Inamrinone
Why is the use of phosphodiesterase inhibitors limited?
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
