Heart Failure Drugs

Question 1

1. How does chronic heart failure cause heart remodeling?

Answer 1

Hypertrophy can lead to ischemic changes, impairment of diastolic filling, and alterations in ventricular geometry (remodeling) by local ATII and aldosterone that facilitate heart remodeling and fibrosis

Remodeling includes cardiac dilation and slow structure changes, including connective tissue is proliferated, and myocardiac cells with fetal cell features, and cardiac cells die by accelerated apoptosis

Question 2

What two drugs and cardiomyopathy condition that decrease contractility with loss of myocardium (eg, MI),

Answer 2

β-blockers (acutely),
non-dihydropyridine Ca2+ channel blockers,

Dilated cardiomyopathy

Question 3

Drugs that ↓ preload:

Answer 3

digoxin, diuretics, ACEIs, ARBs, and venodilators (nitro drugs)

Question 4

Drugs that ↓ afterload:

Answer 4

digoxin, ACEIs, ARBs, and arteriodilators: CCBs, hydralazine, fenoldopam, K channel opening drugs (minoxidil and diazoxide), nitro drugs

Question 5

Drugs that ↑ contractility:

Answer 5

digoxin
beta agonists: dobutamine
PDE III inhibitors: Inamrinone and milrinone

Question 6

Drugs that ↓ remodeling of cardiac muscle:

Answer 6

ACEIs, ARBs, spironolactone, beta blockers

Question 7

PRIMARY TREATMENTS FOR CHF

Answer 7

Positive Inotropic agents
Digitalis (Digoxin)
Bipyridines/ PDE inhibitors (Inamrinone and milrinone)
Beta-adrenergic agonists (dobutamine)

Other agents (not positive inotropic agents):
Diuretics (Spironolactone and eplerenone)
ACE-I, ARB and aliskiren
Vasodilators (Nesiritide, Bosentan)
Beta-adrenergic blockers (carvedilol, metoprolol, - increase NO)

Question 8

2. Which drugs decrease heart remodeling and increase survival in heart failure?

Answer 8

ACEI, ARB
Spinorolactone, eplerenone
Carvedilol, metoprolol

Question 9

3. What is the MOA of digoxin?

Answer 9

Cardiac glycosides increase contraction of the cardiac sarcomere by increasing the cytosolic free calcium concentration

1. Digoxin binds (competes with K+ ) to and inhibit Na+/K+-ATPase
2. Intracellular sodium concentration is increased

Question 10

4. Why digoxin increase parasympathetic activity?

Answer 10

Autonomic actions: because cytosolic calcium is increased, which triggers Ach and Norepinephrine release from parasympathetic and sympathetic nerve terminal, respectively

Question 11

5. Why digoxin can treat atrial fibrillation?

Answer 11

Parasympathomimetic responses at low dose: inhibit SA, block A-V conduction ( M2 mostly in atrial cells). Blockage of A-V conduction is the MOA for treatment of atrial fibrillation

Question 12

6. What are the ADR of digoxin?

Answer 12

GIT
Anorexia, nausea, vomiting and diarrhea

CNS
Disorientation, hallucination, visual disturbances (altered color perception - digoxin toxicity)
Gynecomastia, rare.

ECG
shortening of the action potential duration due to increased potassium conductance that is caused by increased intracellular calcium
Increased PR interval – caused by decreased AV conduction velocity
Less negative of resting membrane potential, easy premature depolarization
Toxic responses
Can cause any arrhythmia.

Question 13

7. How potassium affect digoxin?

Answer 13

shortening of the action potential duration due to increased potassium conductance that is caused by increased intracellular calcium
Increased PR interval – caused by decrease AV conduction

Question 14

8. What is the MOA of amrinone and milrinone? When do you use them?

Answer 14

Acts by inhibiting the enzyme phosphodiesterase-3.
which increases cAMP in:
heart muscle = increase inotropy - contractility
smooth muscle = decrease TPR - vasodilation

cAMP phosphorlyates MLCK and inactivates MLCK
D1, B2 agonist, milrinone

Uses: Only IV for short term therapy
Only for ACUTE heart failure

or severe exacerbation of CHF.

Question 15

9. What is the MOA of nesiritide?

Answer 15

cGMP dephosphorylates MLC

is recombinant human BNP approved for treatment of acute decompensated CHF

producing potent venous and arteriolar vasodilation

Question 16

10. How do you treat chronic heart failure?

Answer 16

Limit physical activity
Reduce weight
Reduce water intake
Control hypertension
Na+ restriction
Diuretics
Angiotensin antagonists
Digoxin
Beta blockers
Vasodilators

Question 17

11. What are the symptoms of acute left heart failure?

Answer 17

Symptoms: 
Orthopnea: sit up
Dyspnea even sit up at rest
Pink sputum
Sweating
Anxiety
Physical signs:
Whole lung rales
Gallop heart rate
Cyanosis

CXR:
Heart enlarge
Butterfly infiltration

Question 18

12. How do you treat acute heart failure?

Answer 18

1. O2
2. Morphine IV or IH (calm down patient)
3. Furosemide IV
4. Digoxin IV (no repeat until 4 h later)
5. Nitroprusside iv fusion, quickly reduce both artery and venous pressure (remember avoiding light, wrapping all tube and bag in foil paper)—why?
6. Life support
7. Treat the cause (surgery to correct valvular disorders)

Question 19

13. Does ACEI decrease both preload and afterload?

Answer 19

Yes, slows remodeling

Question 20

14. How CVS drugs change EDV and ESV and SV and HR?

Answer 20

If they decrease preload (EDV) and afterload (EDV)
If they decrease CO that also decreases SV and HR
pulse pressure also decrases SV

Question 21

15. What is the MOA of ivabradine? Sacubitril?

Answer 21

Inhibits SA node funny (if) channel, reduces heart rate but does not suppress heart contraction

Sacubitril is neprilysin inhibitor
Neprilysin is the enzyme to degrade natreuretic peptide (BNP) and bradykinin

In patients with chronic symptomatic heart failure who tolerate an ACE inhibitor or ARB, replacement by an ARNI is recommended to further reduce morbidity and mortality

ARNI ( ARB+ neprilysin inhibitor) (valsartan+ sacubitril)

Question 22

Signs and symptoms in HF

Answer 22

Tachycardia
Decreased exercise tolerance & SOB
Peripheral and pulmonary edema
Myocardial hypertrophy

Question 23

What will reduce exercise tolerance ?

Answer 23

B blocker

Verapamil and Diltiazem