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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