Factors on Cardiac Output Afterload Preload

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Drug acting on the Heart Heart failure

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Lecture objectives At the end of the this lecture, the student will able to: Describe basic anatomy of the heart. List determinants factor of cardiac out put. Describe main approach to the treatment of heart failure. List the names of drug used to treat heart failure and hypertension

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A state in which the heart cannot provide sufficient cardiac output to satisfy the metabolic needs of the body. It is commonly termed congestive heart failure (CHF) since symptoms of increase venous pressure are often prominent

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Cardiac Physiology (remember this?)CO = SV x HR HR: parasympathetic and sympathetic tone SV: preload, afterload, contractility

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Cardiac OutputVolume of blood ejected per minute Averages between 4-6L/min CO = Stroke volume X heart rate =70 ml X 60 beats/min =4,200 ml/min

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PreloadDegree of stretch of myocardial fibers Determined by the volume of blood in left ventricle (LV) at end of diastole Increased volume –> increased preload-> increased cardiac output (CO) Decreased volume –> decreased preload –> decreased cardiac output (CO) Compliance of myocardial cells also affects preload

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Factors Which Increase PreloadIV fluids Blood Vasoconstriction Factors Which Decrease Preload Diuretics Dehydration Hemorrhage Vasodilation

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Afterload Related to arterial pressure or diameter of arteries As pressure increases, resistance increases, afterload increases As pressure decreases, resistance decreases, afterload decreases

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ContractilityForce generated by the myocardium when it contracts – inotropic property Ejection fraction (EF) - percentage of LV end-diastolic volume that is ejected with each contraction EF - normally approximately 50-55%

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Left versus Right FailureLeft Heart Failure - Dyspnea - Dec. exercise tolerance - Cough - Orthopnea - Pink, frothy sputum Right Heart Failure - Dec. exercise tolerance - Edema - JVD - Hepatomegaly - Ascites

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Five main drugs are used Diuretics ACE inhibitors Positive isotropic drugs Vasodilator ß blockers

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1) Diuretics Drugs that accelerate the rate of urine formation. Result: removal of sodium and water They relive distention of the heart by reducing blood volume

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Side Effects Pre-renal azotemia Skin rashes Neutropenia Thrombocytopenia Hyperglycemia ↑ Uric Acid Hepatic dysfunction

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More severe heart failure → loop diuretics Lasix (20 – 320 mg QD), Furosemide Bumex (Bumetanide 1-8mg) Torsemide (20-200mg)

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2) Inhibitors of renin-angiotensin- aldosterone system Renin-angiotensin-aldosterone system is activation early in the course of heart failure and plays an important role in the progression of the syndrome Angiotensin converting enzyme inhibitors Angiotensin receptors blockers Spironolactone

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Angiotensin Converting Enzyme InhibitorsThey block the R-A-A system by inhibiting the conversion of angiotensin I to angiotensin II → vasodilation and ↓ Na retention

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Side effects of ACE inhibitorsAngioedema Hypotension Renal insuffiency Rash cough

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3)Digitalis Glycosides (Digoxin, Digitoxin)The role of digitalis has declined somewhat because of safety concern Recent studies have shown that digitals does not affect mortality in CHF patients but causes significant Reduction in hospitalization Reduction in symptoms of HF

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Digitalis (cont.) Mechanism of Action+ve inotropic effect by ↑ intracellular Ca & enhancing actin-myosin cross bride formation (binds to the Na-K ATPase → inhibits Na pump → ↑ intracellular Na → ↑ Na-Ca exchange Arrhythmogenic effect

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Digitalis ToxicityNarrow therapeutic to toxic ratio Non and cardiac manifestations Anorexia, Nausea, vomiting, Headache, Disorientation Sinus bradycardia and arrest A/V block (usually 2nd degree) Atrial tachycardia with A/V Block Development of junctional rhythm in patients with a fib

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Last Updated: 8th March 2018

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