DRUGS FOR HEART FAILURE ^^
HEART FAILURE • AFTERLOAD – increase in heart failure
• a state in which the heart is unable to pump blood at a • CONTRACTILITY
rate commensurate with the requirements of the body’s
• HEART RATE - ↑ ↓ → ←
tissues or can do so only at elevated filling pressure
ADDITIONAL NOTES:
• a condition in which the cardiac output is insufficient
for the needs of the body - when ↓ CO = ↓ BP x ↓ SVR
• syndrome with many causes that may involve one or - CO is the target of HF
both ventricles
- Diastolic dysfunction → cardiomegaly → congestion
PATHOPHYSIOLOGY
DIAGNOSIS
• Blood tests
• CXR
• ECG
• Echocardiogram
• Stress test
• Cardiac CT scan
• Cardiac MRI
• Coronary angiogram
• Myocardial biopsy
• Systolic dysfunction, with reduced cardiac output and
significantly reduced ejection fraction (< 45%; normal >
60%)
• Diastolic dysfunction often occurs as a result of
hypertrophy and stiffening of the myocardium
SIGNS AND SYMPTOMS
• Confusion APPROACH TO MANAGEMENT OF HEART FAILURE
• Lowered ability to exercise 1) reducing symptoms and slowing progression as much
as possible during relatively stable periods
• Dry hacking cough
2) managing acute episodes of decompensated failure
• PND, Dyspnea, Orthopnea
STAGE A – at high risk for HF but w/o structural heart
• Cardiomegaly
disease or symptoms of HF
• Engorged neck veins
STAGE B – Structural heart disease but w/o symptoms
FACTORS or signs of HF
• PRELOAD – increase in heart failure STAGE C – Structural heart disease with prior or current
symptoms of HF
• classic Frank-Starling relation
STAGE D – Refractory HF
DRUGS FOR HEART FAILURE ^^
DRUGS FOR HEART FAILURE • GI disturbance, hypotension, hypokalemia
I. INOTROPICS • Monitor Digoxin levels (<1ng/L), electrolytes and ECG
a) Cardiac glycosides ANTIDOTE: (MAPS)
b) B1 agonist • Magnesium
c) PDE Inhibitor • Anti-digoxin Fab fragments (Digifab, Digibind)
d) Ca+2 Sensitizers • Potassium normalization
II. VASODILATORS • Synchronizer (Pacemaker)
III. MISCELLANEOUS b) BETA1 AGONIST
a) ACEIs & ARBS • Dopamine, Dobutamine – IV infusion
b) LCZ 696 MOA: increases cAMP → Increases cardiac contractility,
output
c) Diuretics
EFFECTS:
d) Nesiritide
• produces an increase in cardiac output
e) SGLT2 Inhibitors
• decrease in ventricular filling pressure
DRUGS WITH POSITIVE INOTROPIC EFFECTS
“INOTROPICS” USES: Acute HF, Acutely decompensated CHF
a) CARDIAC GLYCOSIDES A/E: tachyarrhythmia (counteract w/ Adenosine)
• White foxglove - Digitalis lanata (1785 – William c) PHOSPHODIESTERASE3 INHIBITOR
Withering)
• Milrinone, Inamrinone – Bipyridines (IV infusion)
• Digoxin (Lanoxin®/Lanoxicap®), Digitoxin
➢ PRIMACOR
• Digoxin = 250 mcg tab 1/day, narrow therapeutic index
MOA: decrease cAMP breakdown → lower PVR →
• CA+2 is primarily for contraction vasodilation
MOA: inhibit Na+/K+-ATPase → inactivate Na+-Ca+2 EFFECTS: increase HR, (+) inotropism
exchanger → accumulation of Ca+2
USES: same as B1 agonist
EFFECTS:
A/E: tachyarrhythmia, hepatotoxicity, hypersensitivity,
• Mechanical effect: (+) Inotropy hypotension
• Electrical effect: (-) dromotropy d) CALCIUM SENSITIZER
USES: • Levosimendan (IV infusion) - SIMENDA
• Given in pts w/ severe HF to shorten time for recovery MOA: ↑ Ca+2 affinity to cardiac troponin C
• Given if w/ concurrent arrhythmia EFFECTS:
• Control rate of atrial fibrillation • ↑ Cardiac output
S/E:hyperkalemia, N&V, confusion, xanthopsia • ↓ vascular resistance = vasodilation (“inodilator”)
DIGITALIS TOXICITY: • USES: same as B1 agonist
DRUGS FOR HEART FAILURE ^^
DRUGS WITHOUT POSITIVE INOTROPIC EFFECTS • NOTE: at risk for hypokalemia
“UNLOADERS”
• K+ SPARING: Spironolactone, Eplerenone
ACE INHIBITORS AND ARBS
• USE: Add-on, Alternative if at risk for
• Captopril, Enalapril, Lisinopril, Perindopril hypokalemia
• Losartan, Candesartan, Valsartan, etc. BETA BLOCKERS
• MOA: Recall from Antihypertensives • Carvedilol, Metoprolol, Bisoprolol, Nebivolol
• EFFECTS: Arteriolar and venous dilation, reduces • MOA: Recall from PCOL1 and Antihypertensives
aldosterone secretion, reduces cardiac remodeling =
• EFFECTS: reduces heart failure mortality
reduce cardiac preload & afterload
MANAGEMENT OF CHRONIC HEART FAILURE
NATRIURETIC PEPTIDE
• Nesiritide – IV infusion (NATRECOR)
• Human BNP analogue
• MOA: dilates arterioles & veins → vasodilation
• EFFECTS: Activates BNP receptors, increases cGMP
• USE: Acutely decompensated HF
NEPRILYSIN INHIBITOR / ANGIOTENSIN RECEPTOR
BLOCKER
• Sacubitril + Valsartan (Entresto®) – LCZ 696
NON-PHARMACOLOGIC THERAPY
• Neprilysin
• CARDIAC RESYNCHRONIZATION THERAPY
• EFFECTS: increases BNP levels; used in combination
with valsartan for heart failure - Resynchronization of right and left ventricular
contraction by means of a pacemaker
VASODILATORS
- CRT devices are used to: Regulate electrical signals,
• Sodium nitroprusside Treat bundle branch book
• Hydralazine + ISDN (BiDil ®) • CORONARY REVASCULARIZATION
• ↓ afterload (Hydralazine), ↓ preload (ISDN) - patients with a massive myocardial infarction and
• Approved only for African Americans acute heart failure
• USE: Pts who cannot be given ACEIs/ARBs • INTRA-AORTIC BALLOON PUMP THERAPY
DIURETICS - Insertion of an intra-aortic pump
• MOA: Increased excretion of salt and water → reduces
cardiac preload and afterload → reduces pulmonary
and peripheral edema
• THIAZIDE & LOOP: HCTZ, Furosemide
• USE: Evidence of fluid overload
