The document discusses congestive heart failure and its treatment with drugs. It provides details on the pathophysiology and classification of heart failure, clinical manifestations such as pulmonary edema and edema, and compensatory mechanisms. It then summarizes the mechanisms and effects of cardiac glycosides like digoxin, including their positive inotropic effects, effects on electrical conduction, and use in reducing symptoms and improving cardiac function in heart failure.

1. CONGESTIVE HEART FAILURE DR. MA. LENY ALDA G. JUSAYAN INTERNAL MEDICINE, FPSECP, RN, RMT Department of Pharmacology

11. CARDIAC FAILURE  VENOUS PRESSURE  CARDIAC OUTPUT  BLOOD PRESSURE  SYMPATHETIC ACTIVITY  RENAL BLOOD FLOW  RENIN ANGIOTENSIN II  ALDOSTERONE  SODIUM RETENTION  CAPILLARY FILTRATION EDEMA

12. NEUROHUMORAL ACTIVATION DURING MYOCARDIAL FAILURE MYOCARDIAL FAILURE  CARDIAC OUTPUT  BLOOD PRESSURE/TISSUE PERFUSION ACTIVATION OF ADRENERGIC SYSTEM ARTERIOLAR CONSTRICTION INCREASED SYSTEMIC VASCULAR RESISTANCE INCREASED RESISTANCE TO EJECTION

14. Pathophysiology of Cardiac Performance Factor Mechanism Therapeutic Strategy 1. PRELOAD (work or stress the heart faces at the end of diastole) increased blood volume and increased venous tone--->atrial filling pressure -salt restriction -diuretic therapy -venodilator drugs 2. AFTERLOAD (resistance against which the heart must pump) increased sympathetic stimulation & activation of renin-angiotensin system ---> vascular resistance ---> increased BP - arteriolar vasodilators -decreased angiotensin II (ACE inhibitors) 3. CONTRACTILITY decreased myocardial contractility ---> decreased CO -inotropic drugs (cardiac glycosides) 4. HEART RATE decreased contractility and decreased stroke volume ---> increased HR (via activation of  adrenoceptors)

30. CLINICAL MANIFESTATIONS:

31. LEFT HEART FAILURE

32. Pulmonary Edema The most severe manifestation of Left Heart Failure Fluid leak into the pulmonary interstitial spaces (Pulmonary congestion/edema) Hypoxia and poor 02 exchange

42. Heart Failure Clinical manifestations : Pulmonary Congestion (L) and Systemic Congestion (R) Right Heart Failure Left Heart Failure Pulmonary fluid overload Peripheral fluid overload

50. “ All the signs of CHF are the consequences of inadequate force of contraction"

55. DRUGS COMMONLY USED IN HEART FAILURE

63. PROPERTIES OF CARDIAC GLYCOSIDES: OUABAIN DIGOXIN DIGITOXIN Lipid solubility (oil/water coefficient) Low Medium High Oral availability (% absorbed) 0 75 > 90 Half-life in the body (hrs) 21 40 168 Plasma protein binding (% bound) 0 <20 >80 Volume of distribution 18 6.3 0.6

70. Direct Electrophysiological Effects: Cellular Action Potential

71. Afterdepolarizations

72. TISSUE OR VARIABLE EFFECTS AT THERAPEUTIC DOSAGE EFFECTS AT TOXIC DOSAGE Sinus node  rate  rate Atrial muscle  Refractory period  Refractory period, arrhythmias Atrioventricular node  Conduction velocity,  refractory period  Refractory period, arrhythmias Purkinje system, ventricular muscle Slight  refractory period Extrasystoles, tachycardia, fibrillation Electrocardiogram  PR interval,  QT interval Tachycardia, fibrillation, arrest at extremely high dosage

100. ACE Inhibitors in Heart Failure

111. DIURETICS

115. From Knauf & Mutschler Klin. Wochenschr. 1991 69:239-250 70% 20% 5% 4.5% 0.5% Volume 1.5 L/day Urine Na 100 mEq/L Na Excretion 155 mEq/day 100% GFR 180 L/day Plasma Na 145 mEq/L Filtered Load 26,100 mEq/day CA Inhibitors Proximal tubule Loop Diuretics Loop of Henle Thiazides Distal tubule Antikaliuretics Collecting duct Thick Ascending Limb

161. Asymptomatic LV Dysfunction Mild to moderate CHF Moderate to severe CHF ACE inhibitor Digoxin Digoxin Beta blocker Diuretics Diuretics ACE inhibitor ACE inhibitor Beta blocker Beta blocker Spironolactone

162. THANK YOU!!!