Congestive Heart Failure

This Slideshare includes the introduction of congestive heart failure, signs and symptoms, pathogenesis, epidemiology, etiology, pathophysiology, classification of drugs which is used to manage CHF, and recent drugs used to manage CHF.

1. CONGESTIVE HEART FAILURE

2. Introduction 2 By Miss. Shruti Rajendra Rudraksha Department of Clinical Pharmacy M. Pharm First year Guide Dr. S. D. P atil Dr. K. R. Patil Mrs. H. E. Choudhary R. C. Patel Institut e of Pharmaceutical Education and Resear ch, Shirpur - 425405, Dist. Dhule (M.S.)

3. 3 C ontent s Definition Signs and Symptoms Pathogenesis Epidemiology Etiology Pathophysiology Classification Recent Drugs

4. 4 Definition Congestive heart failure in which the heart is unable to maintain an adequate circulation of blood in the bodily tissue or to pump out the venous returned to it by veins. It is a chronic progressively condition that affects the pumping power of human heart muscle.

5. 5 Signs Symptoms Exercise intolerance Shortness of breath Fluid retention and swelling Complications Impaired liver function Headache Vomiting Diarrhoea

6. 6 Non Pharmacological Management Diet Compliance Salt- Advise patient to avoid high salt content foods and not to add salt Alcohol- Advice moderate alcohol consumption Exercise- Regular exercise should be encouraged

7. 7 Pathogenesis Renin + Angiotensinogen Angiotensinogen I Angiotensinogen II Peripheral constriction Aldosterone secretion Increase afterload salt and water retention Increased plasma volume Decrease cardiac output Increases preload Increased cardiac workload

8. 8 Sympathetic Nervous System Stimulation = Activation of adrenaline and nor adrenaline cause increase heart rate, increase contractility and peripheral contraction. VENTRICULAR HYPERTROPHY The left ventricular hypertrophy Systolic/Diastolic dysfunction Atrial fibrillation ventricular arrhythmia Congestive Heart Failure

9. EPIDEMIOLOGY 3-5% in the population over 65 years old Between 8% and 16% of those aged over 75 years . 9 I No symptoms with ordinary physical activity (such as walking or climbing stairs) II Slight limitation with dyspnoea on moderate to severe exertion(climbing stairs or walking uphill) III Marked limitation of activity, less than ordinary activity causes dyspnoea( restriction walking distance and limiting climbing to one flight of stairs) IV Severe disability, dyspnoea at rest(unable to carry on physical activity without discomfort) New York Heart Association(NYHA) classification status of the patient with heart failure

10. Etiology 10 CHF is a weakening of heart caused by an underlying heart or blood vessel problem. Cardiomyopathy(weakened heart muscle) Coronary artery disease(cholesterol deposition) Damaged heart valve High blood pressure Congenital heart defects(defect in the structure of heart) Inflammation of heart muscle(myocarditis) Cardiac arrhythmia(irregular heart beat) 🔑

11. 11 Systolic dysfunction Ventricles of the heart are not able to generate enough stroke volume. Decrease in cardiac output and ejection fraction. Reduction in muscle mass (e.g., myocardial infarction) Dilated cardiomyopathy Bradyarrhythmia Diastolic dysfunction Ventricle wall is thickened. Decrease in preload and increase in afterload. Ventricular hypertrophy Infiltrative myocardial disease Myocardial ischemia and infarction Mitral or tricuspid valve stenosis Pericardial disease. Congestive heart failure can result from any disorder that affects the ability of the heart to contract (systolic dysfunction) or relax(diastolic dysfunction). Mainly 2 types: Systolic dysfunction Diastolic dysfunction

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14. Pathophysiology To understand the pathophysiology processes in heart failure, basic understanding of normal cardiac failure is necessary. Cardiac output(CO) is defined as the volume of blood ejected per unit time and is the product of heart rate(HR) and stroke volume (SV) CO =HR *SV Mainly depends upon 4 factors (on the basis of Starling’s law ) 1. Preload- volume and pressure of blood in ventricles during diastole. 2. Afterload- volume and pressure of blood in ventricles during systole. 3. Contractility 4. Heart rate 14

15. 15 1. Reflex sympathetic stimulation to increase myocardial contractility which in turn results in vasoconstriction and increased cardiac workload. 2. Retention of sodium and water to increase venous return and thus cardiac fluid volume to stretch the ventricular fibers and hence increase in force of contraction. 3. Myocardial hypertrophy(increase in size and weight) to increase amount of contractile tissue and hence contractability. When the compensatory mechanism become insufficient or when they are active for a long period they become ineffective and contribute to heart failure.

16. 16 Damage to cardiac myocytes and extracellular matrix leads to changes in the size, shape and function of the heart and cardiac wall stress These changes lead to systemic neurohormonal imbalance This may lead to fibrosis, apoptosis, hypertension, hypertrophy, cellular and molecule alteration, myotoxicity Hemodynamic alterations, salt and water retention Morbidity and mortality Arrhythmia, pump failure HF symptoms dyspnea, edema, fatigue Progressive remodeling and worsening of LV function

17. Compensatory Mechanism Chronic activation of sympathetic system which leads to tachycardia and increased contractility. Renin angiotensin aldosterone system (loss of myocyte and causes hypertrophy which leads to decrease in pumping function). Vasoconstriction and increased afterload. Vasoconstriction occurs due to number of neurohormones like norepinephrine, angiotensin 2 and vasopressin. Vasoconstriction increases peripheral vascular resistance and hence decreases cardiac output. Ventricular hypertrophy and remodeling. 17

18. Classification Angiotensin converting enzyme - Captopril, Enalapril, Ramipril Angiotensin receptor blocker- Candesartan, Losartan, Telmisartan Beta adrenoreceptor blocker- Atenolol, Carvedilol, Metoprolol Diuretic - Bumetanide, Furosemide, Hydrochlorothiazide Direct vasodilator- Hydralazine, Isosorbide dinitrate Ionotropic agent- Digoxin, Dobutamine Aldosterone antagonist- Spironolactone 18

19. ACE Inhibitor 19

20. Decrease Angiotensin 2 causes- Decrease output of sympathetic nervous system Increase vasodilation of vascular muscles Decrease retaining of sodium and water Increase levels of Bradykinin Decreases preload and afterload Increases cardiac output 20 20 Phloretin Contraindication- Pregnant women 1.Postural hypotension 2. Renal insufficiency 3.Dry cough Adverse effects

21. CAPTOPRIL Mechanism of action Inhibits ACE hence inhibits the conversation of angiotensin II: Reduce afterload and preload Reduction in aldosterone secretion Reduce Na+ and water reabsorption Adverse effects: Cough due to increase in the plasma level of bradykinin. Angioedema Hyperkalemia Teratogenicity Hypotension 21

22. 22 Angiotensin receptor blocker It improve systolic function Reverse cardiac remodeling Decrease sympathetic outflow from CNS Inhibition of renin release. Losartan Mechanism of action Angiotensin II, a vasoconstrictor is concerned with ventricular remodeling and fluid retention. These drug inhibit the binding of angiotensin II to its AT1 receptor These agents do not exert any action on bradykinin and thus do not produce cough. Has comparable effect to ACE I Can be used in certain conditions when ACE I are contraindicated. Adverse drug reaction Hypotension Impairment of renal functioning

23. 23 Beta blocker Mechanism of action Standard beta blocker- Reduction in damaging sympathetic influences in the heart(tachycardia, arrhythmia, remodeling) Inhibition of renin release Carvedilol Beta blockade effect Peripheral vasodilation via alpha 1 adrenoreceptor blockade

24. ADVERSE EFFECTS Bronchoconstriction Can produce some CNS symptoms like depression and sleep disturbance 24

25. 25 Diuretics It relieves pulmonary congestion and peripheral edema Reduce symptoms of volume overload Decrease plasma volume and venous return(preload) to heart. Decrease cardiac work and decrease oxygen demand Decrease plasma volume decreases after load decreases blood pressure They increase salt and water elimination Decreases blood volume Decreases venous pressure

26. 26 Furosemide Mechanism of Action of Loop Diuretics : Loop diuretics act on the Na-K-2Cl symporter in the thick ascending limb of the loop of Henle to inhibit sodium and chloride reabsorption. Because magnesium and calcium reabsorption in the thick ascending limb is dependent on sodium and chloride concentration. Loop diuretics cause vasodilation of the veins and of the kidney’s blood vessels , mechanically causing a decrease in blood pressure. The collective effects of decrease blood volume and vasodilation on decrease blood pressure.

27. DIRECT VASODILATOR Hydralazine Mechanism of action- These agents reduce pulmonary congestion and increase cardiac output by reducing preload or afterload. They also prevent remodeling of heart. Nitrate receptor which is present on smooth muscle possess –SH group which reduces nitrates to nitrite and nitric oxide. NO itself gets converted to an intermediate reactive nitrosothiol which activates intracellular guanylate cyclase(GC) to convert GTP to cGMP results in vascular smooth muscle relaxation. 27

28. ADVERSE EFFECTS Flushing face, palpitation, dizziness, tolerance develop rapidly used orally in sustained release form or transdermally or by IV infusion without drug free interval. DRUG INTERACTION Sildenafil and other vasodilator potentiate the hypotensive action of nitrates(inhibit the metabolizing enzyme PDE-IV and potentiate further release of cGMP) sudden death occurs. 28

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30. 30 Contraindications Ventricular fibrillation, ventricular tachycardia, digitalis toxicity Adverse reaction Fatigue, headache, blurred yellow or green vision, seizures

31. 31 ALDOSTERONE ANTAGONIST SPIRONOLACTONE These enhances diuresis by promoting Na+ and water excretion (while retaining K+) and prevents myocardial as well as vascular fibrosis which is responsible for pathological remodeling of heart. ADVERSE EFFECTS Hyperkalemia is major risk during the therapy and require serum K+ monitoring. Gynecomastia may occur in male patients after long term use.

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33. 33 MANAGEMENT AND TREATMENT LAB FINDINGS BUN (Blood Urea Nitrogen) Liver Function Test Kidney Function Test B type Naturetic peptide test(BNP) SURGICAL TREATMENT Coronary Artery Bypass Graft Surgery Valve Surgery Left ventricular Reconstruction Passive Cardiac Support Artificial Cardiac Pacemaker Cardiac transplantation Implantable Cardiovascular Defibrillation Ventricular Assist Devices

34. RECENT DRUGS Cardiac myosin activator (Omecamtive Mecarbil) 34 They accelerate transition of actin- myosin complex from a weakly bound to strongly bound configuration. Increase myosin head interaction with actin Decrease nonproductive ATP hydrolysis Increase duration of action further increase in stroke volume hence improvement in myocardial systolic function and increases oxygen consumption.

35. VASODILATOR SERELAXIN Recombinant human relaxin- 2 Relaxin- circulating peptide found in pregnant women Regulates systemic vasodilation Improves dyspnea significantly. 35

36. 36 THANKS…! Suggesstions Please…….