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    Drug Heart Failure M

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    Athari Khan
    Congestive heart failure is a condition where the heart cannot pump enough blood to meet the body's needs. It can be caused by impaired heart muscle contraction or an increased workload on the heart. The main types are systolic and diastolic heart failure. Signs include increased heart rate, fatigue, shortness of breath, swelling, and poor exercise tolerance. Causes include coronary artery disease, hypertension, valvular heart disease, and cardiomyopathy. Treatment involves drugs like ACE inhibitors, diuretics, cardiac glycosides, and vasodilators to reduce preload and afterload on the heart and increase contraction.

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    Drug Heart Failure M

    Uploaded by

    Athari Khan
    56 views24 pages
    Congestive heart failure is a condition where the heart cannot pump enough blood to meet the body's needs. It can be caused by impaired heart muscle contraction or an increased workload on the heart. The main types are systolic and diastolic heart failure. Signs include increased heart rate, fatigue, shortness of breath, swelling, and poor exercise tolerance. Causes include coronary artery disease, hypertension, valvular heart disease, and cardiomyopathy. Treatment involves drugs like ACE inhibitors, diuretics, cardiac glycosides, and vasodilators to reduce preload and afterload on the heart and increase contraction.

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    Drug Heart Failure m

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    Congestive heart failure is a condition where the heart cannot pump enough blood to meet the body's needs. It can be caused by impaired heart muscle contraction or an increased workload on the heart. The main types are systolic and diastolic heart failure. Signs include increased heart rate, fatigue, shortness of breath, swelling, and poor exercise tolerance. Causes include coronary artery disease, hypertension, valvular heart disease, and cardiomyopathy. Treatment involves drugs like ACE inhibitors, diuretics, cardiac glycosides, and vasodilators to reduce preload and afterload on the heart and increase contraction.

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    56 views24 pages

    Drug Heart Failure M

    Uploaded by

    Athari Khan
    Congestive heart failure is a condition where the heart cannot pump enough blood to meet the body's needs. It can be caused by impaired heart muscle contraction or an increased workload on the heart. The main types are systolic and diastolic heart failure. Signs include increased heart rate, fatigue, shortness of breath, swelling, and poor exercise tolerance. Causes include coronary artery disease, hypertension, valvular heart disease, and cardiomyopathy. Treatment involves drugs like ACE inhibitors, diuretics, cardiac glycosides, and vasodilators to reduce preload and afterload on the heart and increase contraction.

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    of 24

    CONGESTIVE HEART FAILURE

    DEFINITION
    Congestive heart failure is a condition in which the heart is unable to to pump sufficient blood to meet the needs of the body.

    It can be caused by an impaired ability of the heart muscle to contract or an increased workload imposed on the heart.

    A clinical syndrome caused by an accumulation of fluid peripherally (right ventricular failure) or in the lungs (left ventricular failure), or both, from inadequate functioning of the heart. Congestive heart failure is a complication of an underlying disease process. Systolic heart failure (the more common form) is due to impaired systolic pumping action of the heart. Diastolic heart failure occurs when the systolic function is normal but the filling of the heart is impaired.

    Types of heart failure

    Systolic dysfunction or systolic heart failure: The ventricles are dilated and unable to develop sufficient wall tension to eject adequate quantity of blood.

    Diastolic dysfunction or diastolic heart failure: The ventricular wall is thickened and unable to relax properly during diastole, ventricular filling is impaired and output is low.

    Signs & symptoms of congestive heart failure heart rate. Rapid muscular fatigue. Short breath due to pulmonary edema Myocardial hypertrophy ( size of heart) Renal output Congestion (excessive amount of fluid) in the

    chest
    Poor exercise tolerance. Tachycardia.

    Main causes/Etiology of CHF



    Coronary artery disease (atherosclerosis) Long standing hypertension Valvular heart disease Congenital heart disease
    Dilated cardiomyopathy (disease associated with
    enlargement of left ventricle)

    Ischemic heart disease/Myocardial infarction

    Prevalence and incidence


    It is currently approximated that about 23 million people are suffering from CHF globally. In developed countries between 1% and 2% of the adult population have CHF. It particularly affects the elderly (>65 years) and in this age group 6-10% suffer from CHF. Each year CHF is diagnosed in about 3 per 1000 in the population, but the incidence is much higher (10 per 1000) in the elderly. The lifetime risk of developing heart failure is one in five for a person at the age of 40 years.

    In 2010,estimated total cost of heart failure in the United States was $39.2 billion, representing 1-2% of all health care expenditures.

    Mortality is greater than 50% for patients in USA.

    Factors aggravating heart failure (Risk factor)

    Myocardial ischemia or infarction Dietary sodium excess Excess fluid intake Arrhythmias Conditions associated with increased metabolic demand (eg pregnancy, thyrotoxicosis, excessive physical activity) Administration of drug with negative inotropic properties or fluid retaining properties (e. NSAIDs, corticosteroids) Alcohol Advancing age Coronary artery disease and previous heart attacks High blood pressure Diabetes High cholesterol Thyroid disease Kidney disease

    Preventive measures:
    Tobacco cessation and avoidance of smoke. Limit alcohol consumption. Increase daily activity. Decrease emotional stress. A diet high in vegetables and fruits is recommended.

    Management

    Drug therapy: vasodilators, ACE inhibitors, Diuretics,


    Anti-arrhythmic drug therapy, blockers, Cardiac glycosides

    Treat the cause/aggravating factors Supportive oxygen, bed rest, elevation of head of bed Surgery revascularization to treat ischemia

    Pharmacologic Interventions
    Four classes of drugs are currently recommended to manage congestive heart failure: 1. 2. 3. 4. Angiotensin-converting enzyme (ACE) inhibitors Diuretics Cardiac glycosides Nitrates or direct vasodilators.

    A stepwise approach is often used. Step 1: ACE inhibitors (e.g., captopril Step 2: Diuretics (e.g., furosemide) Step 3: Cardiac glycosides (e.g., digoxin) Step 4: Nitrates or vasodilator (e.g., topical nitroglycerin)

    Non-pharmacological measures for the management of heart failure


    Diet ensure adequate general nutrition and, in obese patients, weight reduction

    Salt advise patients to avoid high salt content foods and not to add salt (particularly in severe cases of congestive heart failure)
    Fluid urge overloaded patients and those with severe congestive heart failure to restrict their fluid intake Alcohol advise moderate alcohol consumption (abstinence in alcohol related cardiomyopathy) Smoking avoid smoking (adverse effects on coronary disease) Exercise regular exercise should be encouraged

    Drugs for congestive heart failure


    1. Vasodilators Captoprol Enalapril ACE inhibitors Fosinopril Lisinopril Hydralazine Sodium nitroprusside 2. Diuretics Bumetanide Furosemide Hydrochlorothiazide Metolazone 3. Inotropic agents Digitoxin Cardiac glycosides Digoxin Dobutamine b-adrenergic agonist Amrinone Phosphodiesterase inhibitor Milrinone

    Drug treatment of heart failure Three main sites of pharmacological attack


    Pre-load After-load

    By reduce venous pressure By reduce peripheral resistance

    Pre-load: is the volume of blood that fills the ventricle during diastole. Elevated pre-load causes overfilling of the heart which increases the workload of heart After-load: is the pressure (due to increased PR) that must be overcome for the heart to pump blood into the arterial system. Elevated after-load causes the heart to work harder to pump blood into the arterial system.

    Pathology of Heart Failure & Drug Target


    Pre-load Heart disease C.O. After-load

    Vasodilator

    Venous pressure

    Positive inotropes Renal blood flow Renin release Angiotensin II

    Tissue perfusion

    ACE inhibitor

    Aldosterone Na+ & H2O retension Edema

    Diuretics

    Drugs that reduce pre-load


    Diuretics Loop diuretics (eg frusemide): mainly act on ascending loop of Henle (powerful diuretic): acute heart failure, severe chronic heart failure (CHF). Thiazide diuretics (eg hydrochlorothiazide): act on early distal tubule: suitable alternative for mild to moderate CHF. Spironolactone (aldosterone antagonist): given in combination with above diuretics reduces K+ loss. Improves survival in severe heart failure. Veno-dilator pre-load reducers Therapeutic use: Sodium nitroprusside particularly appropriate if acute failure associated with acute ischaemia. M/A: Dilatation of arterioles and venules, so peripheral resistance and venous pressure, preload .effective in heart failure.

    Reduction of after-load
    Angiotensin converting enzyme inhibitors (ACEI) - reduce peripheral resistance through blocking

    formation of angiotensin II and cause natiuresis through inhibition aldosterone production and prolong life in CHF patients. AII receptor blockers
    - may be alternative if ACEI not tolerated because of cough.

    Increase myocardial contraction


    Inotropic drugs
    Cytoplasmic Ca2+ concentration Cardiac muscle contractility Cardiac output

    Inotropic agents Digitoxin Digoxin Amrinone Milrinone


    Phosphodiesterase inhibitor Cardiac glycosides

    Dobutamine b-adrenergic agonist

    M/A of Digoxin
    Digitalis Inhibition of Na+-K+ ATPase Na+-K+ pump N Intracellular Na+

    Inhibition of Na+/Ca2+ exchange Intracellular Ca2+ Interaction of actin and myosin cardiac contractility Heart size & HR

    M/A of Digoxin
    Ca2+ Ca2+ Na+ Na+

    K+

    Digoxin

    ATPase

    Ca2+

    Ca2+

    Na+

    Na+

    K+

    SR
    Ca2+

    Digoxin
    Therapeutic uses Contraindication
    Arrhythmia Heart block Ventricular tachycardia Renal failure Hypokalemia

    1. Congestive heart failure


    2. Left vetricular failure

    Adverse effects
    Nausea, vomiting Cardiac arrythmias Confusion Hypokalemia Skin rash Gynecomastia (due to prolong use)

    Hypercalcemia

    Pharmacokinetics
    Route of admn: oral Plasma t1/2: 5-7 days (digitoxin) 40 hrs (digoxin) Plasma protein binding: 95%(digitoxin) 25% (digoxin) Metabolized by liver and excreted with bile in the gut, thus has longer t1/2

    b-adrenergic agonist (Dobutamine)

    Dobutamide is the most commonly used inotropic agent other than digitalis. It is given by intravenous infusion and primary used in the treatment of acute heart failure in hospital setting.

    M/A of b-adrenergic agonist (Dobutamine)


    b-adrenergic agonist
    Binds to b-adrenergic receptor Activates adenylyl cyclase Catalyzed ATP to produce cAMP

    PDE inhibitor

    PDE

    AMP

    cAMP activates protein kinase which phophorylates Ca2+ channel and Ca2+ flow into cell force of contraction of heart muscle

    M/A of b-adrenergic agonist & PDE inhibitor


    Ca2+
    Ca2+ channel

    Binding of b-adrenergic agonist activates adenynyl cyclase which produce cAMP

    b-adrenergic receptor

    Adenynyl cyclase

    Ca2+

    ATP

    cAMP

    PDE

    AMP

    SR
    Ca2+

    Phosphorylates Ca-channel & Ca2+ flow into cell

    activates
    Amrinone

    Protein kinase A (Active)

    PDE: phosphodiesterase inhibitor

    b-adrenergic agonist (Dobutamine) Therapeutic uses Congestive heart failure Acute myocardial infarction Cardiac decompensation that may occur

    after cardiac surgery


    Pharmacokinetics Plasma t1/2: 2 min Route of admin: IV Adverse effect Increase BP and HR

    Increase Myocardial infarction


    by increasing oxygen demand

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