Drugs for Heart Failure

Question 1

Symptoms seen with heart failure

Answer 1

Dyspnea
Fatigue
Palpatations

^^seen in both types

Question 2

Diastolic HF

Answer 2

Increased LV pressure/LV can’t relax
–too much calcium

LA can’t pump blood to LV

Don’t tolerate tachycardia well

Question 3

Systolic HF

–what changes are seen in the heart?

Answer 3

Decreased number of cells
Giant cells
Decreased capillary density
Decreased mitochondrial protein
Increased contraction due to fetal actin and myosin
Increased fibroblasts

Question 4

What causes the changes seen in systolic HF?

Answer 4

Too much

• NE
• AT II
• Aldosterone
• Proinflammatory cytokines

Possibly endothelin and vasopressin

Question 5

What are digitalis glycosides used for?

Answer 5

To improve fxn in systolic HF
–mild positive ionotropes

Comes from foxglove

DIGOXIN

Question 6

What drugs increase CO in HF?

Answer 6

Digoxin

Dobuatmine

Question 7

What drugs are used to relieve edema in HF?

Answer 7

Diuretics

• -often furosemide first
• -spironolactone
  
  • –aldosterone antagonist

Question 8

What drugs are used to decrease angiotensin II?

Answer 8

ACE inhibitors
ARBs if severe cough with ACE inhib

Improve quality of life

Question 9

What drugs are used to decrease peripheral resistance with HF?
Why?

Answer 9

isosorbide dinitrate
hydralazine
–decreases tone

to unload stressed heart
to decrease mortality

Question 10

What drugs are used to decrease HR in HF?

Answer 10

Beta blockers

• -can decrease mortality and improve quality of life
• -start with low dose

Carvedilol is especially good

• -blocks beta 1, beta 2, and alpha 1
• -has antioxidant effect
• -decreases remodeling!!!!

Question 11

What treatments increase survival in CHF?

Answer 11

Spironolactone
ACE inhibitors
Vasodilators
Beta blockers

Question 12

How does digoxin induce inotropy?

Answer 12

Inhibits Na/K ATPase in plasma membrane of myocyte and call Na+ accumulates

Increase in Na+ decreases the gradient

Since Na+ gradient drives the Ca2+ extrusion during depolarization, the reduced Na+ gradient leads to less Ca2+ extrusion by the Na+/Ca2+ exchange

Ca2+ accumulates!!! –> exactly what you want when there is not enough Ca2+

Question 13

Vagal effects of digitalis glyocsides

Answer 13

Action on brain stem
–strong cardiac slowing

Also some direct slowing of conduction in heart due to partial depolarization

Glycosides may still be used in atrial tachycardias when other drugs don’t work

Question 14

Toxicity of cardiac glycosides

• -therapeutic index
• -three common symptoms

Answer 14

Low therapeutic index (~2)
–have to be careful!

Three common symptoms

• -anorexia, nausea
• -arrhythmias
• -neurologica
  
  • -headache, drowsiness, confusion
  • -green, yellow vision

Question 15

How do you treat cardiac glycoside toxicity?

Answer 15

KCl when K+ low
Antiarrhythmic drugs
Atropine for excess vagal activity
Digoxin AB!!

Question 16

What drugs are used for systolic heart failure?

Answer 16

Beta blockers are first line
–slow HR to increase diastole and allow better filling

Some CCBs may decrease ventricular stiffness
Verapamil decreases HR

ACE inhibitors prevent remodeling but may lower BP

Diuretics useful since these patients develop significant congestions
–often hypotension results

Question 17

Nesiritide

Answer 17

Use for sypnea in serious HF

• -peptide given IV
• • t1/2 = 18 min

Causes vasodilation and natriuresis (relieves edema)
–acts on GPCR to increase cGMP and NO

Known as BNP

Question 18

Milrinone

Answer 18

Caffeine analog
Positive inotrope for HF

Inhibits PDE-3, specific for heart and blood vessels

Good therapeutic index
(compared to digoxin)

S/E mild - fever, some hepatotoxicity