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2. 2 CONGESTIVE HEART FAILURE Is a complex, progressive disorder in which the heart is unable to pump sufficient blood to meet the demands of the body. Is a complex, progressive disorder in which the heart is unable to pump sufficient blood to meet the demands of the body.

3. Causes Left systolic dysfunction: MC cause Left systolic dysfunction: MC cause Myocardial infarction Myocardial infarction Hypertensive heart disease Hypertensive heart disease Valvular heart disease Valvular heart disease Dilated cardiomyopathy Dilated cardiomyopathy Congenital heart disease Congenital heart disease Arteriosclerotic heart disease Arteriosclerotic heart disease 3

4. Symptoms Dyspnea Dyspnea orthopnea orthopnea paroxysmal nocturnal dyspnea paroxysmal nocturnal dyspnea fatigue fatigue fluid retention(edema) fluid retention(edema) 4

5. 5 Consequences of Heart Failure CO DECREASES CO DECREASES DECREASE IN BLOOD PRESSURE DECREASE IN BLOOD PRESSURE RBF DECREASES RBF DECREASES INCREASES ANGIOTENSIN II INCREASES ANGIOTENSIN II PERIPHERAL RESISTANCE INCREASES PERIPHERAL RESISTANCE INCREASES INCREASES ALDOSTERONE INCREASES ALDOSTERONE

6. 6 Consequences of Heart Failure SODIUM AND WATER RETENTION SODIUM AND WATER RETENTION BLOOD VOLUME INCREASES BLOOD VOLUME INCREASES MAY RESULT MAY RESULT  PERIPHERAL EDEMA  INCREASED PRELOAD  PULMONARY EDEMA

7. Compensatory responses to HF Increased sympathetic stimulation Activation of RAASystem Myocardial hypertrophy 7

8. 8 COMPENSATORY MECHANISMS SYMPATHETIC ACTIVITY INCREASES SYMPATHETIC ACTIVITY INCREASES  BETA RECEPTORS STIMULATED  HR INCREASES  FORCE OF CONTRACTION INCREASES  ALPHA RECEPTORS STIMULATED causing vasoconstriction  VENOUS RETURN INCREASES  PRE LOAD INCREASES

9. Activation of the Renin-Angiotensin System: Activation of the Renin-Angiotensin System: ↓CO →↓BP →↓RBF→↑RAAS→↑Na &H20 retention→ ↑Blood vol→↑venous return→↑venous press→edema ↓CO →↓BP →↓RBF→↑RAAS→↑Na &H20 retention→ ↑Blood vol→↑venous return→↑venous press→edema Myocardial hypertrophy: initial hypertrophy leads to stronger contraction but at the longer run will result in inability to eject blood(systolic dysfunction) and inability to relax to accept blood(diastolic dysfunction) Myocardial hypertrophy: initial hypertrophy leads to stronger contraction but at the longer run will result in inability to eject blood(systolic dysfunction) and inability to relax to accept blood(diastolic dysfunction) 9

10. 10 DECOMPENSATED HEART FAILURE DECOMPENSATED HEART FAILURE - If compensatory Mech restore cardiac output, then the failure is said to be compensated heart failure. - If the adaptive mechanism fails which occurs at the long run – Decompensated Heart failure

11. Non pharmacologic treatment PHYSICAL ACTIVITY based on patient-to-patient basis PHYSICAL ACTIVITY based on patient-to-patient basis DECREASE SODIUM IN DIET DECREASE SODIUM IN DIET STOP SMOKING STOP SMOKING 11

12. Drugs used Renin-Angiotensin system blockers Renin-Angiotensin system blockers β- blockers β- blockers Diuretics Diuretics Inotropic agents Inotropic agents Direct vasodilators Direct vasodilators Aldosterone antagonists Aldosterone antagonists 12

13. Goal of pharmacologic intervention in HF Alleviate symptoms: decrease ECF volume and load on the myocardium Alleviate symptoms: decrease ECF volume and load on the myocardium Slow disease progression Slow disease progression Improve survival: by preventing the remodeling of the heart, improve cardiac contractility Improve survival: by preventing the remodeling of the heart, improve cardiac contractility 13

14. Drugs contraindicated in HF Calcium channel blockers Calcium channel blockers NSAIDS NSAIDS Excessive Alcohol intake Excessive Alcohol intake They exacerbate HF They exacerbate HF 14

15. Strategy to use of drugs One or more of the drug classes are administered One or more of the drug classes are administered 15

16. 16 IONOTROPIC AGENTS CARDIAC GLYCOSIDES aka DIGITALIS CARDIAC GLYCOSIDES aka DIGITALIS  DIGOXIN  DIGITOXIN BETA AGONIST BETA AGONIST  DOPAMINE  DOBUTAMINE PHOSPHO DIESTERASE INHIBITORS PHOSPHO DIESTERASE INHIBITORS  AMRINONE  MILRINONE

17. 17 CARDIAC GLYCOSIDES MECHANISM: Direct INHIBIT of cardiac Na ⁺ /K ⁺ ATPase pump esp K ⁺ INHIBIT of cardiac Na ⁺ /K ⁺ ATPase pump esp K ⁺ INTRACELLULAR SODIUM INCREASES INTRACELLULAR SODIUM INCREASES Na ⁺/Ca²⁺ DECREASES Na ⁺/Ca²⁺ DECREASES intracellular Ca++ INCREASES intracellular Ca++ INCREASES FORCE OF CONTRACTION INCREASES FORCE OF CONTRACTION INCREASES

18. 18 CO INCREASES resembling that of a normal heart CO INCREASES resembling that of a normal heart Reduced SYMPATHETIC activity Reduced SYMPATHETIC activity HR DECREASES HR DECREASES HEART OXY. DEMAND DECREASES HEART OXY. DEMAND DECREASES

19. Mechanism: Indirect Mechanism: Indirect Inhibition of neuronal Na ⁺/K⁺ ATPase Inhibition of neuronal Na ⁺/K⁺ ATPase Resulting in ↑ vagal stimulation →↓HR & myocardial oxygen demand Resulting in ↑ vagal stimulation →↓HR & myocardial oxygen demand 19

20. 20 USES SEVERE LEFT VENTRICULAR SEVERE LEFT VENTRICULAR SYSTOLIC FAILURE SYSTOLIC FAILURE SUPRAVENTRICULAR TACHYCARDIAS Acute management of CHF NOT FOR : MILD OR MODERATE FAILURE MILD OR MODERATE FAILURE RIGHT HEART FAILURE RIGHT HEART FAILURE DIASTOLIC FAILURE DIASTOLIC FAILURE

21. 21 PHARMACOKINETICS DIGOXIN DIGOXIN  SHORT HALF LIFE  FAST ONSET OF ACTION therefore useful in emergency  EXCRETED UNCHANGED IN URINE DIGITOXIN DIGITOXIN  PROTEIN BINDING EXTENSIVE  Slower onset of action  METABOLISM - LIVER  EXCRETION - STOOL

22. 22 SIDE EFFECTS CVS: Ventricular tachyarrhythmias: most serious adverse effect CVS: Ventricular tachyarrhythmias: most serious adverse effect DO NOT IMPROVE SURVIVAL DO NOT IMPROVE SURVIVAL GIT: anorexia, nausea, vomiting GIT: anorexia, nausea, vomiting CNS : headache, fatigue CNS : headache, fatigue Vision disturbance, halos on dark objects, alteration of color perceptionVision disturbance, halos on dark objects, alteration of color perception MONITOR DRUG LEVELS IN RENAL AND HEPATIC DISEASEMONITOR DRUG LEVELS IN RENAL AND HEPATIC DISEASE

23. 23 DIGITALIS TOXICITY PREDISPOSING FACTORS PREDISPOSING FACTORS Electrolyte : Hypokalemia, hypercalcemia, hypomagnesemia Electrolyte : Hypokalemia, hypercalcemia, hypomagnesemia DRUGS – loop diuretics or thiazide DRUGS – loop diuretics or thiazide (TREATMENT – K sparing diuretic or KCl) (TREATMENT – K sparing diuretic or KCl) Quinidine, verapamil &amiodarone: by displacing digoxin from protein binding sites & by competition for renal excretion Others: renal failure, myocarditis, hypoxia

24. Management of digoxin toxicity Anti-digoxin antibody (Fab antibody) Anti-digoxin antibody (Fab antibody) Supportive therapy: electrolytes and Lidocaine Supportive therapy: electrolytes and Lidocaine 24

25. BETA BLOCKERS Benefits of beta blockers : Benefits of beta blockers : Prevent changes that occur in the heartbecause of chronic activation of the sympathetic system: decreasing heart rate and inhibiting the release of renin Prevent changes that occur in the heartbecause of chronic activation of the sympathetic system: decreasing heart rate and inhibiting the release of renin Two common beta blockers used: carvedilol and metoprolol Two common beta blockers used: carvedilol and metoprolol 25

26. 26 BETA AGONISTS MOA: increases force of contraction MOA: increases force of contraction Dopamine Dopamine Dobutamine : must be used in a hospital setting for the treatment of acute HF Dobutamine : must be used in a hospital setting for the treatment of acute HF Mostly slow IV route.

27. 27 PHOSPHODIESTERASE INHIBITORS AMRINONEMILRINONE Mech: c AMP INCREASES Mech: c AMP INCREASES CYTOPLASM CALCIUM LEVELS ↑ CYTOPLASM CALCIUM LEVELS ↑ SE: THROMBOCYTOPENIA SE: THROMBOCYTOPENIA

28. DIURETICS MOA:DECREASE PLASMA VOL MOA:DECREASE PLASMA VOL VENOUS RETURN DECREASES VENOUS RETURN DECREASES WORKLOAD DECREASES WORKLOAD DECREASES OXY. DEMAND DECREASES OXY. DEMAND DECREASES Uses: reduce symptoms of vol overload: orthopnea and PND Uses: reduce symptoms of vol overload: orthopnea and PND 28

29. 29 DIURETICS Furosemide Furosemide Bumetanide Bumetanide Torsemide Torsemide Hydrochlorothiazide Hydrochlorothiazide LOOP DIURETICS THIAZIDE DIURETICS

30. 30 Inhibitors of Renin-Angiotensin System ACE INHIBITORS ACE INHIBITORS Angiotensin-receptor blockers Angiotensin-receptor blockers decrease preload (through venodilation) decrease preload (through venodilation) decrease afterload (through arteriolar dilation) decrease afterload (through arteriolar dilation) or both or both

31. 31 ACE INHIBITORS ENALAPRIL ENALAPRIL CAPTOPRIL CAPTOPRIL LISINOPRIL LISINOPRIL QUINAPRIL QUINAPRIL FOSINOPRIL FOSINOPRIL ACTS BY INHIBITING THE enzyme ACE, WHICH CAUSES DECREASE IN ANGIOTENSION II. LEADS VASODILATION, DECREASED PRELOAD & AFTERLOAD DECREASE Na & H20 Retention Decrease inactivation of bradykinin

32. 32  Angiotensin II is one of most potent vasoconstrictors known  -leads to increased systolic and diastolic blood pressure  -acts directly on adrenal cortex leads to increased secretion of aldosterone

33. 33 decreased angiotensin II leads to decreased peripheral resistance leads to decreased afterload decreased angiotensin II leads to decreased peripheral resistance leads to decreased afterload decreased aldosterone secretion leads to decreased salt & water retention leads to decreased preload decreased aldosterone secretion leads to decreased salt & water retention leads to decreased preload decreased degradation of bradykinin leads to increased kinin activity ie. leads to increased vasodilation. decreased degradation of bradykinin leads to increased kinin activity ie. leads to increased vasodilation.

34. Therapeutic use Pts with mild dyspnea on exertion and do not show signs or symptoms of volume overload Pts with mild dyspnea on exertion and do not show signs or symptoms of volume overload In pts with ejection fraction of <35% In pts with ejection fraction of <35% Immediately in pts who have had a recent MI to decrease cardiac remodeling Immediately in pts who have had a recent MI to decrease cardiac remodeling 34

35. Adverse effects Postural hypotension Postural hypotension Renal insufficiency Renal insufficiency Hyperkalemia Hyperkalemia Angioedema Angioedema Persistent dry cough Persistent dry cough CI: IN PREGNANCY-FETOTOXIC CI: IN PREGNANCY-FETOTOXIC 35

36. Angiotensin receptor blockers Are competitive antagonists of angiotensin type 1 receptor. Are competitive antagonists of angiotensin type 1 receptor. Have actions similar to those of ACE inhibitors Have actions similar to those of ACE inhibitors Have no effect on bradykinin Have no effect on bradykinin Are a substitute for ACE-I in those patients who cannot tolerate ACE-I with severe cough or angioedema Are a substitute for ACE-I in those patients who cannot tolerate ACE-I with severe cough or angioedema 36

37. Losartan Losartan Telmisartan Telmisartan Valsartan Valsartan 37

38. Adverse effects Similar to ACE-I but does not cause dry cough or angioedema Similar to ACE-I but does not cause dry cough or angioedema Are contraindicated in pregnancy Are contraindicated in pregnancy 38

39. 39 DIRECT VASODILATORS HYDRALAZINE HYDRALAZINE ISOSORBIDE ISOSORBIDE MINOXIDIL MINOXIDIL SODIUM NITROPRUSSIDE SODIUM NITROPRUSSIDE ACT BY DIRECT VASODILATION. Causing decrease in preload and afterload ACT BY DIRECT VASODILATION. Causing decrease in preload and afterload

40. Aldosterone antagonist SPIRONOLACTONE: SPIRONOLACTONE: MOA: Prevents salt and water retention, myocardial hypertrophy and hypokalemia MOA: Prevents salt and water retention, myocardial hypertrophy and hypokalemia Reserved for advance cases of HF Reserved for advance cases of HF Prevents cardiac remodeling Prevents cardiac remodeling Pts should not be taking potassium supplements while on this drug Pts should not be taking potassium supplements while on this drug ADVERSE EFFECTS: gastritis, peptic ulcer, confusion, gynecomastia, menstrual irregularities, decreased libido ADVERSE EFFECTS: gastritis, peptic ulcer, confusion, gynecomastia, menstrual irregularities, decreased libido 40

41. 41 FIRST LINE FIRST LINE ACE inhibitors ACE inhibitors Diuretics Diuretics Cardiac Glycosides Cardiac Glycosides SECOND LINE LOOP DIURETICS DIRECT VASODILATORS BETA AGONISTS

42. summary ↓ preload: diuretics, ACE-Is, ARBs and venodilators ↓ preload: diuretics, ACE-Is, ARBs and venodilators ↓ afterload: ACE-Is, ARBs and arteriodilators ↓ afterload: ACE-Is, ARBs and arteriodilators ↑contractility: digoxin, beta agonists ↑contractility: digoxin, beta agonists ↓ remodeling of heart: ACE-Is, ARBs, Spironolactone ↓ remodeling of heart: ACE-Is, ARBs, Spironolactone 42