Drugs for heart failure

Question 1

inhibits sodium/potassium pump thereby decreasing calcium expulsion via Na-Ca exchanger
-at low dose decreases HR (SA node) and conduction velocity of AV node by prolonging refractory period
At high dose, cardiac arrhythmias
-inhibited by potassium (drug binding) & magnesium (calcium loading)
-enhanced by calcium
* use for heart failure + afib
CONTRAINDICATED in WPW with afib

Answer 1

digitalis/digoxin

*on EKG: therapeutic level increases PR interval and decreases QT interval

Question 2

bipyridine compounds which cause inhibition of phosphodiesterases (these normally inactivate cAMP and cGMP) -> inhibits PDE-3

• increase calcium influx
• positive inotropic effects
• most of benefit is from venodilation
• only available in parenteral forms & used for acute heart failure or severe exacerbation of chronic heart failure, especially when there has been insufficient improvement with conventional vasodilators

Answer 2

inamrinone
milrinone

Tox of inamnirone: nausea, vomiting, arrhythmias, thrombocytopenia, liver enzyme changes
Milrinone: less marrow and liver tox

*Note: chronic milrinone therapy is associated with increased mortality (probably from ventricular arrhythmias) and is only used short-term in hospitalized patients

Question 3

sensitizes troponin to calcium
inhibits phosphodiesterases
venodilation

Answer 3

levosimendan (not approved in USA)

Question 4

beta-1 selective agonist
synthetic analog of dopamine
increases CO
decreases ventricular filling pressure
-can stimulate angina
shift the Frank-Starling curve up -> increased SV

Answer 4

dobutamine
(and dopamine, if increased bp is needed)
*used in stress tests

Question 5

What are first line drugs used for heart failure?

Answer 5

1. diuretics
2. ACE inhibitors
3. angiotensin receptor antagonists
4. aldosterone antagonists
5. beta blockers
   (in acute failure, use diuretics and vasodilators)

Question 6

diuretic drug of choice in heart failure

• reduces venous pressure
• reduces ventricular preload
• reduces salt and water retention in edema
• reduced cardiac size leads to improved pump efficiency
• loop agent

Answer 6

furosemide

*Adverse: fall in CO, hypokalemia, hypomagnesemia -> both cause arrhythmias

Question 7

aldosterone antagonist diuretics

• aldosterone may cause myocardial and vascular fibrosis and baroreceptor dysfunction, so this can decrease morbidity and mortality in patients on ACE inhibitors
• consider use in all patients with moderate or severe heart failure

Answer 7

spironolactone

eplerenone

Question 8

What are some ACE inhibitors used to treat heart failure? Why?

Answer 8

captopril or enalapril reduces peripheral vascular resistance and therefore afterload
also reduce aldosterone secretion, so decrease salt and water retention, reducing preload
-decreased angiotensin also decreases sympathetic activity
-reduce long-term remodeling of heart and vessels
-Use ACE inhibitor for LV dysfunction but no evident of edema
Note: do not replace digoxin with ACE inhibitor, because can cause deterioration

Question 9

Why are angiotensin receptor blockers used for heart failure? Name 2.

Answer 9

losartan and candesartan have limited benefit but are used in patients who are intolerant of ACE inhibitors because of cough

Question 10

synthetic form of endogenous brain natriuretic peptide (BNP)
-increases cGMP in smooth muscle cells and reduces venous and arteriolar tone
Effects are:
1. rapid potent vasodilation
2. decreased intracardiac pressures
3. augment forward CO
4. decreases renin-angiotensin-aldosterone system
5. decreases sympathetic responses
6. promotes diuresis
-administered as a bolus then followed by continuous infusion

Answer 10

nesiritide

Adverse: hypotension, significant renal damage & death

nesiritide is Natrecor
-use only in patients who cannot tolerate or do not respond to IV nitroglycerin or nitroprusside

Question 11

isosorbide dinitrate/hydralazine combination used in African American patients for heart failure

Answer 11

BiDil

Question 12

What are signs of digoxin toxicity?

Answer 12

vision changes
GI disturbances
cardiac arrhythmia
If severe, do not give antiarrhythmic because automaticity will likely be depressed and cause arrest; do not cardiovert -> only shock for vfib

Question 13

pure arteriolar vasodilator

Answer 13

hydralazine

Question 14

What conditions would you use digoxin?

Answer 14

heart failure with afib,
afib, aflutter, PSVT
less commonly used as antiarrhythmic because of effectiveness of beta-blockers, calcium channel blockers, amiodarone

Question 15

Why does hypokalemia exacerbate digitalis toxicity?

Answer 15

further inhibition of the sodium potassium pump
This is a concern when digitalis is used with diuretics.
Hypomagnesemia & hypercalcemia can also promote dig toxicity

Question 16

Why can dobutamine be used in heart failure and dopamine not?

Answer 16

Dobutamine and dopamine both stimulate beta 1 receptors to increase cardiac contractility. Dopamine at high doses stimulates alpha receptors and causes vasoconstriction, increasing HR and afterload.
Dobutamine has balanced action of alpha1 vasoconstriction and beta2 vasodilation.

Question 17

decreases NaCl reabsorption in the distal convoluted tubule

use in mild chronic failure

Answer 17

hydrochlorothiazide