Heart Failure Pharmacology

Question 1

What are the stages of heart failure

Answer 1

Question 2

What are the staples of HF therapy

Answer 2

Diuretics + salt/fluid restriction AND

ACE/ARB + BB

Question 3

What are ARNIs and effect

Answer 3

Angiotensin Receptor Blocker/Neprilysin Inhibitor

More Natriuretic Peptide effect (more vasodilat), Less AT1 effect (less vasoconstriction)

Question 4

Eligibility for ARNI

Answer 4

–EF <35%, NYHA II-III

–GFR >30, K <5.0

–SBP >95mmHg

–On stable dose of ACE-I/ARB

• BEWARE hypotension
• Do NOT use if h/o angioedema

Question 5

Aldosterone antagonists and side effects

Answer 5

•Spironolactone: Old drug, cheap

–Adverse Effects: Hyperkalemia* (increase in deaths seen after widespread use), 10% gynecomastia

•Eplerenone: New drug, expensive, less gynecomastia

–Adverse Effects: Hyperkalemia

Question 6

BB shown to have mortality benefit in HFrEF, what is the benefit

Answer 6

Metoprolol XL (succinate), Carvedilol, Bisoprolol (Europe)

The beneft of BB is primarly CHRONIC – reduce arrhythmia, protect from adverse effects of chronic adrenergic stimulation, lead to reverse remodeling

Question 7

Adverse effects of beta blockers

Answer 7

Adverse Effects: Hypotension, bradycardia, depression, erectile dysfunction, AV block, bronchospasm (rarely)

CAUTION with dosing in acute decompensated heart failure – the abrupt negative inotropic effects of BB can worsen the decompensation

Question 8

Effects of ISDN/Hydralazine and adverse effects

Answer 8

Vasodilator therapy, causes afterload reduction

Mortality benefit in Black pts who are optimized on BB/ACE-I (A-HeFT study)

Adverse Effects: Headache, dizziness, hypotension

Question 9

Broad treatment for patient profile. (4 states)

Answer 9

Question 10

Warm and Wet treatment

Answer 10

Diuretics + Afterload Reduction

Question 11

Diuretics used for HF

Answer 11

Loop diuretics are staple – use IV at least BID

Thiazide diuretics are add-on therapy if loop diuretics reaching high doses without significant effect (Metalazone)

Question 12

What is the significance of JVP

Answer 12

• Surrogate measurement for intravascular volume
• Measuring central venous pressure (CVP), which is surrogate for right atrial pressure (RAP), which can be surrogate for pulmonary capillary wedge pressure (PCWP), which is a surrogate for LV end diastolic pressure (LVEDP)

Question 13

Purpose of afterload reduction in HF

Answer 13

• Heart failure causes activation of the Renin-Angiotensin-Aldosterone system
• Decreased cardiac output à diminished renal blood flow à activation of RAAS

–ATII increases afterload (vasoconstriction) + Na/H2O retention in kidney

–Aldosterone increases Na/Fluid absorption in kidney

Question 14

Approad to beta blockers with HF

Answer 14

Question 15

Treatment stapes for cold and wet

Answer 15

Diuretics + Afterload Reduction + Inotropes

Question 16

Actions of inotropes and examples

Answer 16

Increase CO by increasing contractility

Adrenergic agents stimulate α/β1 receptors: Dopamine, Dobutamine

PDE 3 inhibitor decreases cAMP degradation à increased intracellular Ca à increased contractility: Milrinone

Question 17

MOA of inotropes

Answer 17

Adrenergic agents stimulate the B receptors -> cAMP increase -> increased intracellular calcium -> contraction

PDE3 inhibitors decrease the breakdown of cAMP -> increased intracellular Ca -> contraction

Question 18

Adverse effects of inotropes

Answer 18

Dopamine and dobutamine: increase HR and tachychardia

Milrinone: drop in BP, caution in renal failure

Question 19

Effect of nitroprusside

Answer 19

Pure afterload reduction (arterial dilation), excellent to reduce afterload (SVR) without changing preload, dropping BP/MAP (sometimes MAP comes up due to decreased SVR so improved CO)

Question 20

MOA of digoxin and effect

Answer 20

• Na+, K+ - ATPase inhibitor
• Mechanism: Increase intracellular Na+ -> increase Na+/Ca++ exchange -> increase intracellular Ca++ -> increase contractility

•Anti-arrhythmic effect

Question 21

Signs of digoxin toxicity

Answer 21

• Digoxin toxicity: Confusion, nausea/vomitting, diarrhea, bradycardia, ECG findings. Classically associated with yellow vision
• Suspected toxicity: Check level, check/correct electrolytes, stop digoxin, Digi-bind (Fab antibody) in extreme cases or hyperkalemia (K > 5.5)

Question 22

Drugs that make HFrEF worse

Answer 22

Question 23

NON-PHARMACOLOGIC THERAPY
HFrEF

Answer 23

• ICD (Internal Cardiac Defibrillator) to prevent sudden arrhythmic cardiac death
• CRT (Cardiac Resynchronization Therapy) = Bi-ventricular pacemaker in patients with LBBB
• Advanced Therapies: Transplant, Ventricular Assist Device (VAD)