9 Heart Failure Drugs

Question 1

What are the effects of digoxin?

Answer 1

• positive inotrope
  
  • increases contractile state of myocardium
  • increases SV
• increases vagal tone
  
  • decreases HR
• arterial/venous dilation (decreased venous pressure)

**shifts frank-starling curve to I+V point

Question 2

What is the MOA of digoxin?

Answer 2

• inhibits Na/K ATPase
  
  • increases intracellular Na -> decreases drive to extrude Ca via Na/Ca exchanger- -> indirect increase in intracellular Ca
• K competes for binding of digoxin to Na/K ATPase

Question 3

What are some side effects of digoxin?

Answer 3

Affects all excitable tissues:

• GI tract (N/V/D)
• Visual disturbances
• Neurologic (hallucinations)
• Muscular
• Cardiac (arrhythmias)

**toxicity enhanced with hypokalemia

Question 4

What is the clinical use of digoxin?

Answer 4

Limited to heart failure patients with LV systolic dysfunction in atrial fibrillation (or in sinus patients with continued symptoms despite maximal therapy)

Question 5

What are the effects of diuretics?

Answer 5

• promote elimination of Na and water -> reduce intravascular volume -> decreased venous return
• decreased preload= no longer in range promoting pulmonary congestion
  
  • ​reduce EDP without reducing SV (move to point D on frank starling curve)

Question 6

Describe furosemide

Answer 6

• loop diuretic (potent)
• widely used (many heart failure patients require chronic loop diuretic therapy to maintain euvolemia)
• promotes K loss -> hypokalemia

Question 7

Describe chlorothiazide

Answer 7

• thiazide diuretic
• rarely used alone
  
  • use in combo therapy with loop diuretics in patients refractory to loop diuretics alone
• promotes K loss -> hypokalemia

Question 8

Describe amiloride

Answer 8

• K-sparing diuretic
• weak diuretic activity but limits K and Mg wasting
  
  • commonly used in combo therapy

Question 9

Describe triamterene

Answer 9

• K-sparing diuretic
• weak diuretic activity but limits K and Mg wasting
  
  • commonly used in combo therapy

Question 10

What are the effects of angiotensin II?

Answer 10

1. potent arterial constrictor (increases BP)
2. Na and water retention (via aldosterone stimulation)
3. promote neuronal and adrenl medulla catecholamine release -> enhances sympathetic activity
4. arrhythmogenic
5. promotes cardiac remodeling (hypertrophy, fibrosis, apoptosis)

Question 11

What are the effects of aldosterone?

Answer 11

1. promotes Na and water retention
2. promotes K secretion
3. promotes cardiac remodeling (fibrosis)

Question 12

What are the effects of ACE inhibitors?

Answer 12

• decrease systemic vascular resistance (afterload)
  
  • block constricting activity of Ang II
• reduce intravascular volume and systemic/pulmonic congestion
  
  • block Ang II/aldosterone retention of Na and water
• limit maladaptive ventricular remodeling

Question 13

Describe captopril

Answer 13

• ACE inhibitor
  
  • decrease vascular resistance/afterload
  • block Ang II/aldosterone retention of Na and water
  • limit maladaptive ventricular remodeling

Question 14

Describe enalapril

Answer 14

• ACE inhibitor
  
  • decrease vascular resistance/afterload
  • block Ang II/aldosterone retention of Na and water
  • limit maladaptive ventricular remodeling

Question 15

What are some side effects of ACE inhibitors?

Answer 15

• hyperkalemia (esp when combined with K sparing diuretics)
• angioedema (from bradykinin)
• dry cough (from bradykinin)
• hypotension
• renal failure

Question 16

Describe angiotensin receptor blockers

Answer 16

• competitively block AT1 receptor
• do NOT prevent degradation of bradykinin
• potential alternative for heart failure patients who can’t tolerate an ACE inhibitor

Question 17

Describe losartan

Answer 17

• angiotensin receptor blocker
• potential alternative for heart failure patients who can’t tolerate an ACE inhibitor

Question 18

Describe valsartan

Answer 18

• angiotensin receptor blocker
• potential alternative for heart failure patients who can’t tolerate an ACE inhibitor

Question 19

What are some side effects of angiotensin receptor blockers?

Answer 19

• hypotension
• renal failure
• hyperkalemia (esp with K sparing diuretics)

Question 20

Describe the Valsartan/Sacubitril combination pill

Answer 20

• Valsartan= angiotensin blocker
• Sacubitril= neprilysin inhibitor
  
  • decreases breakdown of vasoactive peptides (ANP, bradykinin, etc)
  • counters the neurohormonal activation that leads to vasocontstriciton, Na retention, and maladaptive remodeling
• Combo= superior to enalapril in reducing risks of death and hospitalizations for heart failure

Question 21

Describe aldosterone antagonists

Answer 21

• decreases fibrosis and adverse ventricular remodeling normally induced by excess aldosterone in heart failure
• improves mortality rates
• reduces symptoms such as…
  
  • edema
  • arrhythmias
  • fibrosis (in myocardium and vessels)

Question 22

Describe spironolactone

Answer 22

• aldosterone antagonist
• decreases fibrosis and adverse ventricular remodeling normally induced by excess aldosterone in heart failure

Question 23

Describe eplerenone

Answer 23

• aldosterone antagonist
• decreases fibrosis and adverse ventricular remodeling normally induced by excess aldosterone in heart failure

Question 24

What is an adverse effect of aldosterone antagonists?

Answer 24

Hyperkalemia

Question 25

What are the types of vasodilators? Give examples

Answer 25

* venous * nitrates * mixed * ACE inhibitors * Ang II inhibitors * nitroprusside * arterial * hydralazine

Question 26

What are the hemodynamic effects of different vasodilators?

Answer 26

* venous * _decreases preload_ (LV EDV) * results in decreased wall stress (little effect on SV) * arterial * _reduces afterload_ (decreases systemic resistance) * results in increased SV and decreased wall stress * mixed * reduces _both preload and afterload_ * results in increased SV and decreased wall stress

Question 27

Describe the isosorbide dinitrate/hydralazine combo

Answer 27

* improves survival in heart failure patients (though less effective than ACE inhibitors) * substitute when not able to tolerate ACE inhor ang blocker (e.g. in renal dysfunction) * more effective in african americans

Question 28

What are the effects of beta blockers on heart failure?

Answer 28

Ultimately stop the chronic sympathetic stimulation that worsens heart failure... * decrease arrhythmias, oxygen demans, and BP * prevent disease progression/remodeling * inhibit cardiotoxic actions of catecholamines * reduce Beta 1 receptor down-regulation \*\*can initially worsen cardiac function, must start at a low dose and gradually increase to maximum dose

Question 29

Describe ivabradine

Answer 29

* slows HR by blocking I_f channels in pacemaker cells * considered for use in heart failure patients with a resting heart rate over 70 bpm (including those already taking a beta blocker) * prolongs survival time

Question 30

Describe the best drugs to use in NYHA classes I-IV

Answer 30

Question 31

What are some non-medication therapies for heart failure?

Answer 31

* salt restriction * rehab/exercise * biventricular pacing/cardiac resynch therapy (CRT) * implantable cardio-defibrillator devices (ICDs) * mechanical circulatory support * ventricular assist devices (VADs) * implantable artificial hearts * heart transplant

Question 32

What therapies are used in heart failure with preserved ejection fraction?

Answer 32

* diuretics (reduce pulmonary congestion/peripheral edema) * caution: avoid underfilling left ventricle * could reduce SV * address correctable causes (e.g. BP) of impaired diastolic function * contractile function preserved (inotropes=useless) * maybe some benefit from RAAS blockade/beta blockers

Question 33

What are some ways to classify acute heart failure?

Answer 33

* "wet"= volume overload consequent of elevated filling pressures (pulmonary congestion/edema) * "cold"= decreased cardiac output consequent of reduced tissue perfusion

Question 34

How would you treat a "warm and wet" patient?

Answer 34

Diuretic and/or vasodilator for pulmonary edema

Question 35

How would you treat a "cold and wet" patient?

Answer 35

diuretic and/or vasodilator for pulmonary edema AND intravenous inotropic therapy to increase cardiac output

Question 36

Describe nitroprusside

Answer 36

* vasodilator for acute heart failure (IV administration) * helpful in patients with severe HF with elevated systemic vascular resistance * direct NO donor that dilates both arteries and veins * reduces preload AND afterload (increases SV)

Question 37

Describe nitroglycerin

Answer 37

* vasodilator for acute heart failure (IV administration) * most commonly used for acute dysfunction due to acute ischemia * primarily induces venodilation and reduces ventricular filling (preload)

Question 38

Describe dobutamine

Answer 38

* inotropic agent for acute heart failure * predominantly affects beta 1 adrenergic receptor stimulation * increases contractility and SV * _little effect_ on peripheral vascular resistance and arterial pressure

Question 39

Describe dopamine

Answer 39

* inotropic agent for acute heart failure (dose dependent pharmacological effect) * low dose (D1 receptors)= renal/mesenteric artery dilation * intermediate dose (D1 and B1 receptors)= renal effect PLUS increases HR and contractility * high dose (D1, B1, a1 receptors)= vasoconstriction

Question 40

Describe milrinone

Answer 40

* phosphodiesterase inhibitor (selective for cardiac/smooth muscle PDE3) * decreases degradation of cAMP * _positive inotropic effect_ (increased CO) * balanced arterial and veno**_dilator_** (decreased preload/afterload) * inotrope + dilation= **_increased stroke volume_**