Drugs used in congestive heart failure

Heart failure

Heart’s ability to pump blood is decreased below that required to maintain adequate circulation

Symptoms are due toSymptoms are due to

Blood back-up behind the failing ventricles

Pathophysiology of CHFPathophysiology of CHF

Left ventricular failureLeft ventricular failureleft ventricle is not able to pump blood

Not able to accept blood from left atrium

Decreased blood flow to atrium from lungs

Pulmonary congestion

Right ventricular failureRight ventricle is not able to pump blood

Not able to accept blood from right atrium

Decreased venous return

Blood stagnation in the peripheral organs

Peripheral edema

SymptomsSymptoms

Definitions Definitions a. Inotropic a. Inotropic – increased FOC– increased FOCb. Chronotropic b. Chronotropic – Increased heart rate– Increased heart ratec. Preload c. Preload – initial stretching of the cardiac – initial stretching of the cardiac

myocytes prior to contraction (venous myocytes prior to contraction (venous return)return)

d. Afterload d. Afterload ––the pressure against which the pressure against which the left ventricle has to push the blood to the left ventricle has to push the blood to the aortathe aorta

e. Cardiac output e. Cardiac output – volume of blood – volume of blood pumped by the heart per minutepumped by the heart per minute

Drugs for CHFDrugs for CHF Angiotensin Converting Enzyme (ACE)

inhibitors: enalapril, lisinopril, captopril, ramipril

AT1 blockers (ARBs): losartan, valsartan Diuretics: furosemide, hydrochlorothiazide,

spironolactone Beta-blockers: metoprolol, bisoprolol,

carvedilol Inotropic drugs: Digoxin Vasodilators: hydralazine, sodium

nitroprusside

Mechanism of Positive Inotropic Mechanism of Positive Inotropic ActionAction

2K+

3Na+3Na+

Ca2+

Na+

Actin & myosin

Digoxin

Ca2+

Ca2+ conc. low

Ca2+ conc. High Cardiac cell

Mechanism of Positive Inotropic Mechanism of Positive Inotropic ActionAction

2K+

3Na+3Na+

Ca2+

Na+

Actin & myosin

Digoxin

Ca2+

Ca2+Ca2+ Ca2+ Ca2+Ca

2+Ca2+

↑↑Ca2+↑↑↑↑Ca2+

Cardiac cell

Digoxin Mechanism of Digoxin Mechanism of ActionAction

Inhibition of cardiac NaInhibition of cardiac Na+ + -K-K++ ATPase ATPase ↑ ↑ intracellular intracellular NaNa+ + ↓ ↓ NaNa++/Ca/Ca2+ 2+ exchange exchange ↑ ↑ intracellular Caintracellular Ca2+ 2+ ↑ ↑ intracellular Caintracellular Ca2+ 2+ release from SR release from SR ↑ ↑ actin-myosin interaction actin-myosin interaction ↑ ↑ contraction contraction ↑CO ↑CO