Heart Failure by siva

Heart failure : 

Heart failure Prepared & Presented by Dr. Siva Reddy Challa , Professor & HOD, Dept. of Pharmacology KVSR Siddhartha College of Pharmaceutical Sciences, Siddhartha Nagar, Vijayawada-520010 Andhra Pradesh, INDIA Email: sivareddypharma@gmail.com

Heart attack and Heart Failure : 

Heart attack and Heart Failure 6 Heart attack (MI) is one of the causes of Heart Failure. Heart attack is followed by Heart failure. But both are not the same.

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Systolic Dysfunction Vs Diastolic Dysfunction

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Image shows a normal heart has normal patterns of Pressures but in case of CHF, pressures will be very high in veins

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JVP- Jugular Vein Pressure is an indication of right heart failure

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Site Normal pressure range (in mmHg ) Central venous pressure 3–8 Right ventricular pressure systolic 15–30 diastolic 3–8 Pulmonary artery pressure systolic 15–30 diastolic 4–12 Pulmonary vein/ Pulmonary capillary wedge pressure 2–15 Left ventricular pressure systolic 100–140 diastolic 3-12 acute pulmonary edema is likely to be present at a PCWP of >20mmHg. It has also been used to diagnose severity of left ventricular failure and mitral stenosis.

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acute pulmonary edema ; this is likely to be present at a PCWP of >20mmHg. It has also been used to diagnose severity of left ventricular failure and mitral stenosis

Pulmonary Edema in Chest X ray: 

Pulmonary Edema in Chest X ray

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Pitting Pedal Edema

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40 Systolic function of the heart is maintained by: Contractility of the myocardium Pre-load After-load Heart rate

Pharmacotherapy is aimed at:: 

41 Pharmacotherapy is aimed at: Decreasing Preload Decreasing After load Increasing Contractility Decreasing Remodeling of cardiac muscles

RX METHODS: 

42 R X METHODS REDUCE PHYSICAL ACTIVITY DECREASE SODIUM IN DIET VASODILATORS DIURETICS INOTROPICS

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VASODILATORS DIURETICS INOTROPICS ACE inhibitors ARBs ( angiotensine receptor blockers) Direct vasodilators : Sodium nitroprusside Hydralazine Nitrates: -Nitroglycerine - Isosorbide dinitrate -Loop diuretics - Thiazides -K Sparring diuretics -Spironolactone -Eplerenone cardiac glycosides ( DigitalisCompounds ) -Digoxin - Digitoxin Beta agonist -Dopamine -Dobutamine Phosphodiesterase inhibitors - Amrinone - Milrinone BETA BLOCKERS - Metoprolol - Carvedilol In chronic CHF, beta blockers have been found to prevent the remodeling changes in the heart.

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44 Vasodilators : Reduce load (Pre & After) on myocardium Diuretics : Decrease extracellular fluid volume (decrease preload) Inotropes : Increase the strength of cardiac muscle contraction.

Arrest / reversal of disease progression and prolongation of survival: 

45 Arrest / reversal of disease progression and prolongation of survival ACE inhibitors / AT1 antagonists Beta blockers Aldosterone antagonists Spironolactone Eplerenone

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46

ACE inhibitors / ARBs: 

47 ACE inhibitors / ARBs ACE inhibitors reduce aldosterone secretion salt and water retention and vascular resistance They are among the first line drugs for Chronic Heart Failure, along with Diuretics

ACE inhibitors: 

48 ACE inhibitors CAPTOPRIL LISINOPRIL ENALAPRIL RAMIPRIL QUINAPRIL FOSINOPRIL BENAZEPRIL MOEXIPRIL

Mechanism of action of ACE inhibitors in Heart Failure: 

49 Mechanism of action of ACE inhibitors in Heart Failure

ACE Inhibitors: 

50 Acts by inhibiting ACE (angiotensin converting enzyme); decrease Angiotensin II levels. Decreased levels of AT-II result in vasodilatation and, decrease in preload & after load These effects result in increased cardiac output Decrease in AT-II arrest/reverse the remodeling changes in the myocardium ACE Inhibitors

Adverse effects of ACE Inhibitors :: 

51 Dry irritating cough Hypotension Hyperkalemia Rashes, Urticaria Angioedema Dysguesia Fetal damage (Teratogenicity) Adverse effects of ACE Inhibitors :

DIURETICS: 

52 DIURETICS LOOP DIURETICS Furosemide Bumetanide POTASSIUM SPARING DIURETICS Spironolactone (an Aldosterone Antagonist) Amiloride Triamterene

DIURETICS: 

53 DIURETICS DECREASE in Plasma Volume DECREASE in Venous Return Cardiac workload DECREASES (Oxygen demand decreases) More efficient cardiac contraction

ALDOSTERONE ANTAGONIST: EPLERENONE: 

54 ALDOSTERONE ANTAGONIST: EPLERENONE Selective aldosterone antagonist Decreases Na and water reabsorption; decreases volume Overload Higher degree of selectivity for aldosterone receptors as compared to Spironolactone. It has low binding affinity for androgen receptors

NESIRITIDE: 

55 NESIRITIDE Recombinant human B-type natriuretic peptide Mechanism of Action Increases cGMP Causes relaxation of arteries and veins

INOTROPIC AGENTS: 

56 INOTROPIC AGENTS

INOTROPIC AGENTS: 

57 INOTROPIC AGENTS CARDIAC GLYCOSIDES (Digitalis compounds) DIGOXIN DIGITOXIN BETA AGONIST DOPAMINE DOBUTAMINE PHOSPHODIESTERASE INHIBITORS AMRINONE MILRINONE

CARDIAC GLYCOSIDES: 

58 CARDIAC GLYCOSIDES Mechanism of Action: INHIBIT SODIUM POTASSIUM PUMP (Na/K ATPase) INTRACELLULAR SODIUM INCREASES CALCIUM EXCHANGE INCREASES CYTOPLASM Ca +2 INCREASES FORCE OF CONTRACTION INCREASES

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61

THERAPEUTIC USES: 

62 THERAPEUTIC USES Severe left ventricular Systolic failure Not For : Mild Or Moderate Failure Other uses: In Atrial fibrillation to control the ventricular rate. Parasympathomimetic Actions of digilatis accomplish this therapeutic objective by decreasing conduction velocity/increasing refractory period of AV node

PHARMACOKINETICS: 

63 PHARMACOKINETICS DIGOXIN SHORT HALF LIFE FAST ONSET OF ACTION EXCRETED UNCHANGED IN URINE DIGI TOXIN EXTENSIVE EXTRAVASCULAR PROTEIN BINDING METABOLISM - LIVER EXCRETION - STOOLS

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64 Digoxin Digitoxin Half-Life (hours) 14 – 60 180 hrs Protein Binding 25% 70 - 90% Route of elimination Renal Hepatic Vagal Stimulation +++ +

DIGOXIN: 

65 DIGOXIN Pharmacological actions : Heart : direct : - increases the myocardial contractility without increasing the oxygen consumption Indirect - vagomimetic and decrease the sympathetic activity

DIGOXIN: 

66 DIGOXIN Heart : increases the force of contraction of the heart in dose dependent manner. Systole is shortened & diastole is prolonged

DIGOXIN: 

67 DIGOXIN Heart : decreases the heart rate -- increased myocardial contractility restores the vagal tone and abolishes the sympathetic over activity Has vagomimetic effect

DIGOXIN: 

68 DIGOXIN Adverse effects : Extra cardiac : anorexia, nausea, vomiting, and visual disturbances Cardiac : ventricular arrhythmias, AV block, bradycardia

DIGITALIS TOXICITY HYPOKALEMIA predisposes to Digitalis toxicity: 

69 DIGITALIS TOXICITY HYPOKALEMIA predisposes to Digitalis toxicity Signs/Symptoms of Digitalis toxicity GIT: anorexia, nausea, vomiting, diarrhea CNS : headache, fatigue, confusion Vision disturbances (blurred vision, alteration of color perception, haloes)

Signs/Symptoms of Digitalis toxicity.: 

70 Signs/Symptoms of Digitalis toxicity. On Heart: Ectopic beats of AV junctional or ventricular origin. Sinus bradycardia First-degree AV block Paroxysmal supraventricular tachycardia Ventricular arrhythmias

Predisposing factors for Digitalis toxicity: 

71 Predisposing factors for Digitalis toxicity Hypokalemia DRUGS – Loop diuretics or thiazide, Quinidine, Verapamil Hypothyroidism Hypoxia

Rx of digitalis toxicity:: 

72 Rx of digitalis toxicity: Stop Digitalis Correction of Potassium deficiency: K + sparing diuretic or KCl Antiarrhythmic drugs ANTI DIGOXIN ANTIBODIES (Digibind)

BETA AGONISTS: 

73 BETA AGONISTS Dopamine Dobutamine What is the disadvantage of Dopamine over Dobutamine and digoxin? Dopamine increases oxygen demand by increasing heart rate Dobutamine increases contractility more than HR (so is a better option in acute CHF as an inotropic agent)

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75

PHOSPHODIESTERASE INHIBITORS Infrequently used drugs; have been shown to increase morbidity and mortality on long-term use (for chronic failure): 

76 PHOSPHODIESTERASE INHIBITORS Infrequently used drugs; have been shown to increase morbidity and mortality on long-term use (for chronic failure) 1. AMRINONE 2. MILRINONE Mechanism of Action: Increase in cAMP by inhibiting phosphodiesterase enzyme causes increase in cytoplsmic Ca +2 concentration. This results in enhanced cardiac contractility

Drugs C/I in CHF:: 

77 Drugs C/I in CHF : Ca +2 channel blockers Beta blockers in high dosage Antiarrhythmic drugs

Role of Beta receptor antagonists: 

78 Role of Beta receptor antagonists Several beta blockers (Metoprolol, Carvedilol) have been shown to reduce progression of Chronic Heart Failure. They have been found to increase the Ventricular ejection fraction, increase exercise tolerance and reduce mortality rate. They are not of value in Acute failure and may be detrimental if systolic dysfunction is marked.

Treatment strategy in systolic failure : 

Treatment strategy in systolic failure

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Thank You This presentaiton is dedicated to my guru Prof. Akula Annapurna Dept . Of Pharmacology Andhra University