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Congestive heart failure
Congestive heart failure (CHF) is a condition where the heart cannot pump enough blood to meet the body's needs. It can be caused by systolic or diastolic dysfunction. Common symptoms include fatigue, weight gain, cough, and shortness of breath. Treatment includes drugs that increase cardiac contractility, reduce fluid retention, block the renin-angiotensin system, dilate blood vessels, and reduce heart rate. New drugs like ivabradine and sacubitril/valsartan may also help lower hospitalization rates.
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Congestive heart failure
- 1. Congestive Heart Failure PresentedBy Shubham Sharma M.Pharmacy Deptt. Pharmacology
- 2. Congestive heart failure(CHF) is a common clinical disorder that results in pulmonary vascular congestion and reduced cardiac output . Heart failure is characterized by the heart’s inability to pump an adequate supply of blood to the body. Heart Failure may primarily be due to systolic dysfunction or diastolic dysfunction. Systolic dysfunction: The ventricles are dilated and unable to develop sufficient wall tension to eject adequate quantity of blood. Diastolic dysfunction: The ventricular wall is thickened and unable to relax properly during diastole , ventricular filling is impaired because of which output is low. It occurs in sustained hypertension , congenital heart disease.
- 4. • Heart failurecan affect the right or left side of your heart, or both at the same time. It can be either an acute (short time) or chronic ( ongoing ) condition. • In acute heart failure, the symptoms appear suddenly but go away fairly quickly. This condition often occurs after a heart attack. • In chronic heart failure , however symptoms are continuous and don’t improve over time. • About 5.7 million Americans have heart failure. The symptoms of heart failure may include: •Excessive Fatigue •Sudden weight gain •A loss of appetite •Persistent coughing •Irregular pulse •Heart palpitations •Shortness of breath
- 7. Etiology of heartfailure: •The most common cause of heart failure is coronary artery disease (CAD). A disorder that causes narrowing of the arteries that supply blood and oxygen to the heart. •Cardiomyopathy, a disorder of the heart muscle that causes the heart to become weak. •A congenital heart defect •A heart attack •Certain types of arrhythmias •High blood pressure •Diabetes •HIV •Severe forms of anemia •Certain cancer treatments, such as chemotherapy •Drug or alcohol misuse
- 8. Systolic heart failureDiastolic heart failure (Contraction) (Relaxation) Blood in lungs Congestion in lungs Congestive heart failure Coronary artery disease Hypertension (Fatty plaque formation) (Increased afterload) Atherosclerosis Increased Blood Pressure
- 9. Coronary artery diseaseHypertension (Fatty plaque formation) (Increased afterload) Atherosclerosis Increased Blood Pressure Decrease Stroke Volume Decrease Cardiac output Structural changes attempt Increase Heart rate Kidney to Increase Stroke volume • Dilated Cardiomyopathy RAAS • Hypertropic Cardiomyopathy
- 11. 1. Inotropic drugs: •Cardiac glycosides : Digoxin, Digitoxin, Ouabain • Sympathomimetics : Dobutamine, Dopamine • Phosphodiesterase ш Inhibitors : Amrinone 2. Diuretics : • High ceiling diuretics : Furosemide, Bumetanide • Thiazide like diuretics :Hydrochlorothiazide, Metolazone 3. Aldosterone antagonist : Spironolactone 4. Inhibitors of Renin – angiotensin system : • ACE- inhibitors : Enalapril, Ramipril • Angiotensin (AT receptor) antagonists : Losartan
- 12. • Vasodilators : •Venodilators : Glyceryl trinitrate • Arteriolar dilator : Hydralazine • Arteriolar + Venodilator : Sodium Nitroprusside 6. ß- adrengeric blockers : Metoprolol, Bisoprolol 7. Others : • Metabolic cardioprotectives : Trimetazidine • Calcium sensitizers : Levosimendan • Levocarnitine
- 15. IN VITRO METHODS: • Isolated Hamster cardiomyopathic heart • Isolated Cat Papillary Muscle (catell and Gold) • Quabain binding IN VIVO METHODS : Rat models : • Rat coronary ligation model • Rat aortic banding model • Dhal salt sensitive rats model • Spontaneous hypertensive rat model
- 16. Dog Models: • Chronic rapid pacing model • Volume overload • Coronary artery ligation and microembolization Rabbit Models : • Volume and pressure overload • Tachycardia pacing model • Doxorubicin cardiomyopathy model Guinea Pig Models : • Cardiac insufficiency model Syrian Hamster Models : • Cardiomyopathic Hamster Transgenic Mice
- 17. Tail Cuff Instrumentused to check blood pressure in rat
- 19. Recent advanced treatmentof congestive heart failure: Two new heart drugs can also help lower your chances of hospital visits because of your heart failure. Ivabradine (Corlanor) : This medication slows your heart rate. It may also cut your time in the hospital. Sacubitril/Valsartan (Entresto) : Lowes says combination of two heart drugs can shorten your time in the hospital. Implantable cardioverter defibrillator : This gives your heart an electric shock, When it senses a life-threatening change in rythum. Cardiac resynchronization therapy : A type of pacemaker, this tiny, implanted device helps your heart beat in regular rythum. Implantable monitor : It lets doctor monitor your heart and adjust your treatment .It measures the pressure on your arteries and your heart rate.It about a size of small paper clip, and it’s inserted into an artery without the needs for batteries or wires. Left ventricular assist device (LVAD) : LVAD’s also pump blood continuously. which makes more efficient than other older options.
- 21. Pathophysiology of Congestiveheart failure
- 25. 1. Inotropic drugs: •Cardiac glycosides : Digoxin, Digitoxin, Ouabain • Sympathomimetics : Dobutamine, Dopamine • Phosphodiesterase ш Inhibitors : Amrinone 2. Diuretics : • High ceiling diuretics : Furosemide, Bumetanide • Thiazide like diuretics : Hydrochlorothiazide, Metolazone 3. Aldosterone antagonist : Spironolactone 4. Inhibitors of Renin – angiotensin system : • ACE- inhibitors : Enalapril, Ramipril • Angiotensin (AT receptor) antagonists : Losartan
- 26. • Vasodilators : •Venodilators : Glyceryl trinitrate • Arteriolar dilator : Hydralazine • Arteriolar + Venodilator : Sodium Nitroprusside 6. ß- adrengeric blockers : Metoprolol, Bisoprolol 7. Others : • Metabolic cardioprotectives : Trimetazidine • Calcium sensitizers : Levosimendan • Levocarnitine
- 28. Digoxin increases theforce of contraction of the muscle of the heart by inhibiting the activity of enzyme (ATPase) that controls movement of calcium, sodium and potassium into heart muscle. Calcium controls the force of contraction.
- 29. Effect on heart: Digitalis causes a dose dependent increase in force of contraction of heart. A positive inotropic action. Effect on blood vessels: Digitalis has mild direct vasoconstrictor action- peripheral resistance is increased in normal individuals. Digitalis has no prominent effect on blood pressure. Systolic blood pressure may increase and diastolic may fall in CHF patients- pulse pressure increases. Effect on kidney : Diuresis occurs in CHF patients, No diuresis Occurs in normal individuals or in patients with edema due to other causes. Effect on central nervous system : Higher dose causes CTZ activation- nausea and vomiting. Still higher doses produce hyperapnoea, central sympathetic stimulation, mental confusion and visual disturbances.
- 30. • Presence offood in stomach delays absorption of digoxin. • The volume of distribution of digoxin is large (6-8L/Kg). • It is concentrated in the heart (~20 times than plasma) , skeletal muscle, liver and kidney. • Digoxin is primarily excreted unchanged by the kidney : mainly by glomerular filtration; rate of excretion is altered parallel to creatinine clearance. • It t1/2 is prolonged in elderly patients and in those with renal insufficiency : dose has to be reduced. i.e. 6-7 days. Adverse effect : • Loss of appetite • Nausea • Bradycardia • Ventricular extrasystoles
- 33. • Furosemide isa prototype drug. • Furosermide works by blocking the absorption of sodium, chloride, and water from the filtered fluid in the kidney tubules, causing a profound increase in the output of urine. •High ceiling loop diuretics are preferred in CHF for rapid mobilization of edema fluid. Pharmacokinetics : Furosemide is rapidly absorbed orally but bioavailability is about 60%. • In severe CHF oral bioavailability may be markedly reduced necessitating parenteral administration. • Lipid solubility is low, and it is highly bound to plasma proteins. • It is partly conjugated with glucuronic acid and mainly excreted unchanged by glomerular filtration as well as tubular secretion. • Plasma T1/2 averages 1-2 hours but is prolonged in patients with pulmonary edema,renal and hepatic insufficiency.
- 35. • ACE inhibitorsproduce vasodilation by inhibiting the formation of angiotension ᴨ . • It is converted to angiotensin ᴨ by angiotensin converting enzyme. • ACE also breaks down bradykinin (a vasodilator substance). Cardiorenal effects of ACE inhibitors : • Vasodilation •Decrease blood volume •Depress sympathetic activity •Inhibit cardiac and vascular hypertrophy
- 40. • Propranolol isa non selective beta receptor antagonist. • It have negative chronotropic and negative inotropic effects on heart. • It decreases oxygen consumption; cardiac work and aortic pressure. • It decreases nor adrenaline and renin releases. It decreases central sympathetic out flow. • It increases oxygen supply and exercise tolerance in angina patients. • It decrease automaticity and abbreviates refractory period of myocardial fibers and decreases rate of depolarization in SA node, Purkinje fibers, and other ectoptic foci. • The drug decreases BP in hypertensive individuals.
- 41. Pharmacokinetics : • Absorption:well absorbed orally, bioavailabity is increased by administering along with food. • Distribution: Widely distributed in a plasma protein bound form. • Metabolism: Metabolized in liver. • Excretion: Excreted through urine Half life of propanolol 4 hours. Side effects : 1.Congestive heart failure is precipitated or aggravated 2.Decreases coronary blood flow 3.Forgetfulness 4.Nightmares 5.Decreases exercise capacity 6.Decreases carbohydrate tolerance 7.Decrease insulin release
- 44. Metabolic cardioprotectives :Trimetazidine
- 45. Calcium sensitizers :Levosimendan
- 46. Two new heartdrugs can also help lower your chances of hospital visits because of your heart failure. Ivabradine (Corlanor) : This medication slows your heart rate. It may also cut your time in the hospital. Sacubitril/Valsartan (Entresto) : Lowes says combination of two heart drugs can shorten your time in the hospital. Implantable cardioverter defibrillator : This gives your heart an electric shock, When it senses a life-threatening change in rythum. Cardiac resynchronization therapy : A type of pacemaker, this tiny, implanted device helps your heart beat in regular rythum. Implantable monitor : It lets doctor monitor your heart and adjust your treatment .It measures the pressure on your arteries and your heart rate.It about a size of small paper clip, and it’s inserted into an artery without the needs for batteries or wires. Left ventricular assist device (LVAD) : LVAD’s also pump blood continuously. which makes more efficient than other older options.
- 47. Precautions and Contraindications •Wear appropriate clothing and shoes for your chosen activity. • Wait one hour after a light meal to exercise. • Avoid activities or exercising outdoors when it is older than 40F or warmer than 80F or on high smog days.