Module C: Drugs for Heart Failure Flashcards
Pathophysiology of Heart Failure
-reduction in SV and CO
- impairs ability of ventricle to fill with blood or to eject blood into circulation
- causes include ischemic heart disease, HTN, arrhythmias, cardiomyopathy
Left Ventricle Heart Failure
- L ventricle does not adequately pump blood- pressure in pulmonary circulation increases- causing pulmonary edema
- reduces diffusion of O2 and CO2 between alveoli and pulmonary capillaries
- causes hypoxemia
- dyspnea, exertion dyspnea, orthopnea, paroxysmal nocturnal dyspnea
-can lead to generalized tissue hypoxia and organ dysfunction
Right Ventricular Heart Failure
- congestion in peripheral veins=ankle edema in ambulatory pt. and sacral edema in bedridden pt.
- leads to hepatojugular reflux (increase in JVD when pressure applied over liver)
- can lead to L sided failure
Goals in Tx of Heart Failure
-improve symptoms, slow or reverse deterioration, and prolong survival
-agents used to Tx include drugs that:
1-increase CO (inotropes and vasodilators)
2-reduce pulmonary and systemic congestion (vasodilators and diuretics)
3-slow or reverse cardiac remodelling (angiotensin inhibitors and sympatholytics)
Positively Inotropic Drugs mode of action and examples
- increase cardiac contractility by increasing intracellular Ca+ levels in cardiac myocytes by increasing cAMP levels, directly or indirectly
- ie. cardiac glycosides, B adrenergic, phosphodiesterase inhibitors (PDI)
Cardiac Glycoside (Digoxin)
- positive inotrope
- used to Tx heart failure associated with afib
- not used as mono therapy, but as an adjunct to other Tx
-mechanism: inhibit Na+/K+ ATPase (enzyme involved in intracellular Na+ regulation), causing increase in Ca+ causing stronger force of contraction
- also has negative chronotropic effects = decreased HR and decreased conductivity because of indirect increase in parasympathetic tone = slows AV node conduction velocity and increases AV node refractory period slowing ventricular rate in afib
- also decreases sympathetic tone
- also directly inhibits sympathetic activity
Digoxin
Adverse Effects
- low therapeutic index (TI)
- toxicities can be arrhythmias, gastrointestinal (nausea/v/d), or CNS (hallucinations, seizures)
-antidote for Digoxin toxicity is antibody: digoxin-immune Fab
B adrenoceptor agonist (Dobutamine)
- positive inotrope
- stimulates cardiac contractility and usually less tachycardia than other B-agonists
- also decreases vascular resistance and cardiac after load = increasing CO
-administered by IV in short-term management of AHF and cariogenic shock
Cons: increased mortality rate with high doses, and caused more arrhythmias than digoxin
Phosphodiesterase Inhibitor (Milrinone)
-positive inotrope
Primacor (Milrinone)
- used in AHF, often when other inotropes are ineffective
- inhibits type 3 phosphodiesterase keeping cAMP levels high, keeping Ca++ high, promoting myocardial cell contraction (increased SV)
- also inhibited in smooth muscle=cAMP remains high, decreasing Ca++ levels, resulting in vasodilation
Phosphodiesterase Inhibitors aka…
Inodilators (inotrope + vasodilator)
-improve SV and vasodilator, decreasing after load
Adverse effects of Milrinone
- thrombocytopenia and ventricular arrhythmias
- fewer toxic effects on bone marrow and liver enzyme function than Amrinone but more likely to cause arrhythmias
Vasodilators
mode of action and types
-reduce preload (venous vasodilator) and/or after load (arteriole vasodilator)
- reduction of preload related to Starling’s Law
- reduction of after load reduces resistance that ventricle pumps against (L ventricle)
- both these reductions help improve SV, and also help decrease edema and congestion
types: angiotensin inhibitors (ACE inhibitors or ARB), and nitrate/hydralazine combination
Angiotensin Inhibitors
- vasodilators
- reduce preload and after load
- counteract adverse effects of angiotensin, mostly its role in cardiac remodelling
- very effective in AHF and CHF and in acute MI
- ARBs less effective than ACE in Tx of HF
- ARBS considered add-ons to ACE inhibitors
Hydralazine and Nitrate
- vasodilators
- hydralazine = arteriole vasodilator (reduces SVR)
- nitrate = venous vasodilator (reduces preload)
- combination of these two used to Tx HF in pt. who cannot tolerate angiotensin inhibitors
Carvedilol (Coreg)
- beta adrenoceptor blocker
- B1 and B2 blocker that also produces vasodilation via a1 receptor blockade
- negative inotropic effect
- sympatholytic
- also has antioxidant properties and anti-inflammatory and antiapoptotic properties
- found to increase L ventricular ejection fraction, improve symptoms and slow disease progression
- currently recommended for pt. wit HF that do not have hypotension, pulmonary congestion or AV blocks
- adverse effects: bradycardia, worsening HF, dizziness
