9 Heart Failure Drugs Flashcards
What are the effects of digoxin?
- 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
What is the MOA of digoxin?
- 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
What are some side effects of digoxin?
Affects all excitable tissues:
- GI tract (N/V/D)
- Visual disturbances
- Neurologic (hallucinations)
- Muscular
- Cardiac (arrhythmias)
**toxicity enhanced with hypokalemia
What is the clinical use of digoxin?
Limited to heart failure patients with LV systolic dysfunction in atrial fibrillation (or in sinus patients with continued symptoms despite maximal therapy)
What are the effects of diuretics?
- 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)
Describe furosemide
- loop diuretic (potent)
- widely used (many heart failure patients require chronic loop diuretic therapy to maintain euvolemia)
- promotes K loss -> hypokalemia
Describe chlorothiazide
- thiazide diuretic
- rarely used alone
- use in combo therapy with loop diuretics in patients refractory to loop diuretics alone
- promotes K loss -> hypokalemia
Describe amiloride
- K-sparing diuretic
- weak diuretic activity but limits K and Mg wasting
- commonly used in combo therapy
Describe triamterene
- K-sparing diuretic
- weak diuretic activity but limits K and Mg wasting
- commonly used in combo therapy
What are the effects of angiotensin II?
- potent arterial constrictor (increases BP)
- Na and water retention (via aldosterone stimulation)
- promote neuronal and adrenl medulla catecholamine release -> enhances sympathetic activity
- arrhythmogenic
- promotes cardiac remodeling (hypertrophy, fibrosis, apoptosis)
What are the effects of aldosterone?
- promotes Na and water retention
- promotes K secretion
- promotes cardiac remodeling (fibrosis)
What are the effects of ACE inhibitors?
- 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
Describe captopril
- ACE inhibitor
- decrease vascular resistance/afterload
- block Ang II/aldosterone retention of Na and water
- limit maladaptive ventricular remodeling
Describe enalapril
- ACE inhibitor
- decrease vascular resistance/afterload
- block Ang II/aldosterone retention of Na and water
- limit maladaptive ventricular remodeling
What are some side effects of ACE inhibitors?
- hyperkalemia (esp when combined with K sparing diuretics)
- angioedema (from bradykinin)
- dry cough (from bradykinin)
- hypotension
- renal failure
Describe angiotensin receptor blockers
- competitively block AT1 receptor
- do NOT prevent degradation of bradykinin
- potential alternative for heart failure patients who can’t tolerate an ACE inhibitor
Describe losartan
- angiotensin receptor blocker
- potential alternative for heart failure patients who can’t tolerate an ACE inhibitor
Describe valsartan
- angiotensin receptor blocker
- potential alternative for heart failure patients who can’t tolerate an ACE inhibitor
What are some side effects of angiotensin receptor blockers?
- hypotension
- renal failure
- hyperkalemia (esp with K sparing diuretics)
Describe the Valsartan/Sacubitril combination pill
- 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
Describe aldosterone antagonists
- 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)
Describe spironolactone
- aldosterone antagonist
- decreases fibrosis and adverse ventricular remodeling normally induced by excess aldosterone in heart failure
Describe eplerenone
- aldosterone antagonist
- decreases fibrosis and adverse ventricular remodeling normally induced by excess aldosterone in heart failure
What is an adverse effect of aldosterone antagonists?
Hyperkalemia
What are the types of vasodilators? Give examples
- venous
- nitrates
- mixed
- ACE inhibitors
- Ang II inhibitors
- nitroprusside
- arterial
- hydralazine
What are the hemodynamic effects of different vasodilators?
- 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
Describe the isosorbide dinitrate/hydralazine combo
- 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
What are the effects of beta blockers on heart failure?
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
Describe ivabradine
- slows HR by blocking If 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
Describe the best drugs to use in NYHA classes I-IV
What are some non-medication therapies for heart failure?
- 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
What therapies are used in heart failure with preserved ejection fraction?
- 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
What are some ways to classify acute heart failure?
- “wet”= volume overload consequent of elevated filling pressures (pulmonary congestion/edema)
- “cold”= decreased cardiac output consequent of reduced tissue perfusion
How would you treat a “warm and wet” patient?
Diuretic and/or vasodilator for pulmonary edema
How would you treat a “cold and wet” patient?
diuretic and/or vasodilator for pulmonary edema
AND
intravenous inotropic therapy to increase cardiac output
Describe nitroprusside
- 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)
Describe nitroglycerin
- 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)
Describe dobutamine
- 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
Describe dopamine
- 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
Describe milrinone
- phosphodiesterase inhibitor (selective for cardiac/smooth muscle PDE3)
- decreases degradation of cAMP
- positive inotropic effect (increased CO)
- balanced arterial and venodilator (decreased preload/afterload)
- inotrope + dilation= increased stroke volume
