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Flashcards in Heart Failure Deck (33):

1. What is the main feature of CHF?

CO (either systolic or diastolic) inadequate to provide O2 that the body needs


2. What is systolic failure of CHF?

Mechanical pumping (CONTRACTILITY) and ejection fraction of the heart are reduced. Tx needs inotropic agents to increase amt of calcium. Do not treat with calcium channel blockers as they reduce contractility and SV.


3. What is diastolic failure of CHF?

Occurs due to stiffening of the heart muscles and loss of adequate relaxation leading to abnormal ventricular filling. Tx with diuretics (to help with pulm edema, but will decrease EDV therefore SV at a certain pt), calcium channel blockers (improved ventricular relaxation and reducing HR to allowing for more time with filling), B-blockers (similar to calcium channel blockers. Positive inotropes ARE NOT used for tx in diastolic failure because they increase outflow obstruction.


4. What is the effect of heart failure on preload?

In both systolic and diastolic heart failure there is an increased preload leading to an increase in SV (due to Frank-Starling curve). At a certain pt when diastolic or systolic dysfunction becomes too severe, the heart is exhausted leading to a decline in SV.


5. What are the different classifications of heart failure described by the AHA?

Stage A → high risk for developing heart failure (HTN, diabetes, CAD, hx of cardiomyopathy)
Stage B → asymptomatic heart failure (previous MI, LV dysfunction, valvular disease)
Stage C → symptomatic heart failure (structural heart disease, dyspnea, fatigue, impaired exercise tolerance)
Stage D → refractory end-stage heart failure (marked symptoms at rest despite maximal medical therapy)


6. Why does the heart rate increase with heart failure?

SV decreases leading to activation of sympathetics (B1-adrenoceptors) and therefore increase in HR


7. What is cardiac remodeling?

During HF, there is a decrease in CO leading to myocardial hypertrophy to maintain cardiac performance. At a certain point there are ischemic changes and diastolic filling impairment. Remodeling refers to the dilation and slow changes of the heart due to increased stress on the heart.


8. What are the neurohumoral compensatory responses to HF?

1. Sympathetic nervous system activation – low bp is detected by the baroreceptors leading to B1-activation increasing both HR and contractility. A1 receptors are also activated causing increased peripheral resistance.
2. RAA activation – decreased CO, decreased blood flow to kidneys stimulating renin release therefore increasing peripheral bp
3. Increased release of ADH and ANP


9. Define positive inotropy.

Increase in cardiac contractility (force)


10. Define positive chronotropy.

Increase in HR


11. Define positive dromotropy.

Increase in conduction velocity


12. Define positive lusitropy.

Increase in rate of relaxation of the heart


13. What is the basis behind long term treatment of HF?

1. RAA inhibition
2. SNS activation
*These decrease amt of cardiac remodeling. Remodeling is irreversible so surgical intervention is the only tx when drugs stop working.
**reduce preload, reduce afterload, enhance inotropic state


14. What classes of drugs are recommended for stages A-D of HF?

Stage A → ACEI, ARB
Stage B → ACEI, ARB, B-blockers
Stage C → diuretics, ACEI, B-blocker [routine drugs], aldosterone antag, ARB, digoxin or hydralazine/isosorbide dintrate [if symptoms do not improve]
Stage D → specialized therapies, continuous support, continuous IV positive inotropic therapy, cardiac transplantation or hospice care


15. What is the role of diuretics for HF patients?

Whenever there is evidence of fluid retention (pulm edema, systemic edema, dyspnea), diuretic therapy is recommended. Diuretics reduce venous pressure and ventricular output. This is not used alone b/c it does not alter the disease progression or survival.
1. Thiazide diuretics (ex. hydrochlorothiazide) → preferred over loop diuretics in pts with elevated bp or only mild fluid retention
2. Loop diuretics (ex. Furosemide) → necessary to restore and maintain euvolemia in HF, better than thiazides b/c they maintain their effectiveness in presence of impaired renal function
3. Aldosterone antagonist (ex. spironolactone) → more useful to prevent cardiac fibrosis and remodeling compared to its diuretic effects


16. What are the different categories of angiotensin inhibitors (indirect vasodilators)?

1. ACE inhibitors → reduce LVEF (stage A, B, C), reduce peripheral resistance and therefore afterload, reduce sympathetic activity, reduce long-term remodeling of the heart and vessels
2. ARBs → use only in pts with stage A, B, C heart failure who are intolerance of ACE inhibitors, Candesartan and valsartan are the only ARBs currently approved for HF
3. Renin inhibitors → recently approved to for HTN and is in clinical trials for HF


17. What category do Hydralazine and Isosorbide Dinitrate fall under?

Direct vasodilators that concurrently improve LVEF


18. What is the MOA of Hydralazine and Isosorbide Dinitrate?

Concurrent use produces sustained improvement in LVEF. These drugs are part of the standard therapy in African Americans with moderately severe to severe HF. They can be used in pts unable to tolerate ACE inhibitors or ARBs due to renal insufficiency or hyperkalemia. These medications are usually given along with a diuretic and B-blocker to counter side effects.
These drugs were combined originally b/c of their complementary hemodynamic actions. Nitrates are venodilators, therefore reducing preload and Hydralazine is a vasodilator that acts primarily on arterial smooth muscle reducing peripheral vascular resistance therefore increasing SV and CO. It is also used to reduce cardiac remodeling. Patients take doses 3 times a day.
Adverse side effects for the combination therapy → Hypotension, reflex tachycardia and Na+ and water retention, headache, dizziness, GI disturbances


19. What category of drugs do Carvedilol and Metoprolol fall under?

B-adrenoceptor antagonists (B blockers) – cardioinhibitory drugs


20. What is the clinical application, MOA and adverse effects for Carvedilol and Metoprolol?

Clinical application → B blockers use to treat HTN, angina, MI, arrhythmias, HF. B-blockers slow disease progression, reduce mortality in pts with HF, reduce LVEF, pts should receive B-blockers even if symptoms are mild or well-controlled with ACE inhibitors and diuretic therapy, also recommended for pt with asymptomatic reduced LVEF (stage B), slows the HR and reduces myocardial oxygen
Mechanism of action → antiarrhythmic effects, slowing or reversing ventricular remodeling, improving LV systolic dysfunction, decreasing HR and ventricular wall stress, inhibiting plasma renin release, negative inotropic effect therefore need to be started at low dose
Adverse effects → drug withdrawal, CV effect (bradycardia, reduced exercise capacity, HF, hypotension, AV block), disturbed lipid metabolism, hypoglycemia, bronchoconstriction, CNS effects
Contraindicated → reactive airway disease (asthma, COPD), pts with sinus bradycardia and partial AV block


21. What category of drugs does digoxin fall under?

Cardiac glycoside, inotropic agent


22. What is the clinical application or Digoxin?

Decreases symptoms of HF but DOES NOT increase survival. Indicated for pts with HF and supraventricular tachyarrhythmias. Should be used with other standard HF therapies in pts with symptomatic HF to reduce hospitalizations. Benefits of digoxin in tx with HF has been due to its positive inotropic effect on failing myocardium and efficacy in controlling the ventricular rate response to atrial fibrillation. Digoxin is both positively inotropic (increases contractility of heart) and negatively chronotropic (decreases heart rate).


23. Explain the positive inotropic effect of Digoxin.

Digoxin is a selective and potent inhibitor of cellular Na+/K+ ATPase allowing for an increase in myocardial intracellular calcium. Inhibition of the Na+/K+ ATPase in vascular smooth muscle causes depolarization which causes smooth muscle contraction and vasoconstriction. Digoxin binds to phosphorylated form of a-subunit of Na+/K+ ATPase. Extracellular K+ promotes dephosphorylation of the enzyme decreasing affinity of enzyme for digoxin.


24. Explain the negative chronotropic effect of Digoxin.

Decreases HR due to increased activation of vagal nerve
**note that at high digoxin concentrations there is an increase in SNS activity increasing the automaticity of the cardiac tissue contributing to development of atrial and ventricular arrhythmias


What is the effect of digoxin on baroreceptors?

Digoxin causes baroreceptor sensitization thereby off setting them in the case of HF leading to sustained elevation of plasma NE, renin, etc


What are the adverse effects of Digoxin?

Digoxin has a narrow therapeutic window and is excreted by the kidneys. Therefore if the pt has kidney damage, there could be an increase in Digoxin concentration leading to toxicity. Toxicity can cause: cardiac effects (atrial tachycardias and AV block), GI effects (anorexia, nausea, vomiting), and CNS effects (headache, fatigue, YELLOW VISION).

Note that also since potassium decreases the affinity of digoxin for the Na+/K+ ATPase then hypokalemia causes increased activity which can lead to toxicity. Hyperkalemia has the opposite effect decreasing digoxin activity and toxicity.

Digoxin-induced arrhythmias - due to hypercalcemia enhancing digoxin-induced increase in intracellular Ca2_+overloading Ca2+ stores

Hypomagnesemia - sensitizes the heart to digoxin-induced arrhythmias


What drugs compete for the digoxin binding site? Other drug-drug reactions?

1. quinidine (class I antiarrhythmic)
2. amiodarone (class III antiarrhythmic)
3. Verapamil

*diuretics cause hypokalemia which can increase digoxin activity


When is Digoxin contraindicated?

Hypothyroidism - increases digoxin concentration
Hyperthyroidism - decreases absorption of digoxin making it less active

-don't use in diastolic fx or right side HF, uncontrolled HTN, bradyarrhythmias, hypokalemics


How do you treat Digoxin induced toxicity arrhythmias?

Lidocaine and or Mg+
severe toxicity - tx with digitalis antibodies that bind and inactivate the drug


What phosphodiesterase III inhibitors can be used to treat acute cardiac failure?

Inamrinone, Milrinone
These are inotropic agents that inhibit PDE III used to treat short-term HF pts. DO NOT USED AS LONG-TERM THERAPY. Inhibition of the enzyme leads to increased cAMP producing positive inotopy causing ARTERIAL AND VENOUS VASODILATION. IV administration.

AE - Arrhythmias, hypotension, thrombocytopenia


Dopamine with HF?

Dopamine is used in the treatment of shock post fluid volume replacement. Dopamine is dose-dependent (D1 then B1 then a1). Dopamine can induce natriuresis increasing urine output, stimulate heart and increase blood flow to kidneys.

AE - cardiac arrhythmias esp at high doses due to increased myocardial oxygen demand


Dobutamine with HR?

B1 agonist used to increase CO in acute HF (cardiogenic shock, MI). Dobutamine is a racemic mixture where (-) is a1 agonist and weakly B1 agonist but (+) is a potent B1 agonist and mild B2 agonist. Vascular effect causes vasodilation and cardiac effect is potent inotropic agent. Dobutamine increases CO without elevating O2 demands which is major advantage over other symp drugs.

AE - less arrhythmogenic compared to dopamine


Glucagon with HR?

cardiac stimulant in management of severe cases of b-blocker overdose - glucagon stimulates adenylyl cyclase to produce increase in cAMP levels leading to positive inotropy and chronotropy.
This means that glucagon is able to produce the same effects as a B-agonist without the need for activating B-receptors thereby preventing B-blocker overdose.