Lesson 36- Cardiac Insufficiency Treatment PDF

Lesson 36 Cardiac Insufficiency 3° Medicine Professor: Vittoria Carrabs PhD Academic year: 2024/25 1. Introduction Heart failure is the end stage of a number of cardiovascular disorders that ultimately impair the ability of the ventricle to fill with blood or to eject bloo...

Lesson 36 Cardiac Insufficiency 3° Medicine Professor: Vittoria Carrabs PhD Academic year: 2024/25 1. Introduction Heart failure is the end stage of a number of cardiovascular disorders that ultimately impair the ability of the ventricle to fill with blood or to eject blood into the circulation Causes: Ischemic heart disease Hypertension Valvular disorders Arrhythmias Viral and congenital cardiomyopathy Constrictive pericarditis Less common: drug-induced (e.g: doxorubicin)  1. Introduction Heart failure is a clinical syndrome where the heart is unable to pump blood effectively to meet the body's demands, leading to symptoms such as dyspnea, fatigue, and fluid retention. General Concepts: The volume of blood the heart pumps per minute, calculated as the product of stroke volume (SV) and heart rate (HR). CARDIAC OUTPUT CO = SV × HR STROKE VOLUME The amount of blood ejected by the left ventricle in one contraction (heartbeat). It is influenced by PRELOAD factors like preload, afterload, and contractility. AFTERLOAD The initial stretching of the heart muscle before contraction, primarily determined by the volume of blood returning to The resistance the heart must the heart (venous return). It reflects the end-diastolic overcome to eject blood during volume. systole. It is influenced by factors such as arterial blood pressure and vascular resistance. 1. Introduction HEART FAILURE HALLMARKS stroke volume and cardiac output Systolic dysfunction Diastolic dysfunction Inability of the ventricles to empty Inability of the ventricles to fill properly Left-sided heart failure: pressure in the pulmonary circulation increases CONGESTION, EDEMA Right-sided heart failure: congestion in the peripheral veins leads to ankle edema 1. Introduction ankle https://youtu.be/b3OHSA7Tz7U?si=sVa-X8fMbLqL-W9B  1. Introduction In patients with heart failure, the goals of therapy are to relieve symptoms, improve quality of life, and prolong survival. Acute heart failure may require hospitalization and the administration of intravenous vasodilators (such as nitrates and nesiritide), diuretics, inotropic agents, and oxygen. Once stabilized, patients can often be managed with oral medications, dietary restrictions, and exercise guidelines 2. Drugs that affect cardiac function DRUGS THAT AFFECT MYOCARDIAL CELLS DIRECTLY CARDIAC GLYCOSIDES DRUGS THAT AFFECT CARDIAC FUNCTION INDIRECTLY CALCIUM ANTAGONISTS  3. Drugs that increase myocardial contraction Controlling factors are: Intrinsic myocardial contractility (depends on [Ca2+ ]i and availability of ATP) Extrinsic haemodynamic factors (elasticity and contractile state of arteries and veins, volume and viscosity of blood) Myocardial contractility depends critically on intracellular Ca2+, and hence on: Ca2+ entry across the cell membrane Ca2+ storage in the sarcoplasmic reticulum. The main factors controlling Ca2+ entry are: Intracellular Na+, which affects Ca2+/Na+ exchange. Catecholamines, cardiac glycosides and other mediators and drugs influence these factors  3. Drugs that increase myocardial contraction CARDIAC GLYCOSIDES Cardiac glycosides come from foxgloves (Digitalis spp.) and related plants A common plant, found both in gardens and the wild, that can be lethal in even small amounts, yet has also been the source of life-saving medication since its discovery in 1775. Digitalis Purpurea Cardiac glycosides (digoxin and digitoxin) are primarily found in the leaves of the plant, but they can also be present in the flowers and roots. Digitalis Lanata 3. Drugs that increase myocardial contraction CARDIAC GLYCOSIDES Their basic chemical structure consists of three components: a sugar moiety, a steroid and a lactone ring 3. Drugs that increase myocardial contraction CARDIAC GLYCOSIDES- DIGOXIN Mechanism of action Digoxin reversibly inhibits the Na-K ATPase enzyme (sodium- potassium pump), leading to an increase in intracellular sodium levels. This indirectly promotes an increase in intracellular calcium, thereby enhancing the contractility of the heart. 3. Drugs that increase myocardial contraction CARDIAC GLYCOSIDES DIGOXIN Actions 1. Cardiac slowing and reduced rate of conduction through the AV node (negative chronotropic effect) 2. Increased force of contraction (positive ionotropic effect) 3. Disturbances of rhythm, especially: Block of AV conduction Increased ectopic pacemaker activity. 4. Extracellular potassium 3. Drugs that increase myocardial contraction CARDIAC GLYCOSIDES NEGATIVE CHRONOTROPIC Effects in rate and rythm ATRIAL FIBRILLATION 3. Drugs that increase myocardial contraction CARDIAC GLYCOSIDES POSITIVE IONOTROPIC Effects in force of contraction 3. Drugs that increase myocardial contraction CARDIAC GLYCOSIDES Effects in extracellular K+ The effects of cardiac glycosides are increased if plasma [K + ] decreases Low K + levels can enhance the effect of digoxin, potentially increasing the digoxin toxicity. The reduced potassium levels increase the binding of digoxin to the Na-K ATPase, making it more effective and raising the likelihood of adverse effects like arrhythmias. Why do you think this might clinically be relevant in patients treated with other concomitant therapies for heart failure? This is clinically relevant in patients with heart failure who are treated with diuretics, such as loop diuretics (e.g., furosemide) or thiazides. These diuretics increase sodium excretion and can also lead to a decrease in potassium levels (hypokalemia) 3. Drugs that increase myocardial contraction CARDIAC GLYCOSIDES Low therapeutic index, serum concentrations are useful in assessing the adequacy of the dosage and evaluating potential toxicity and should be in the range of 0.5 to 2 ng/mL. (NARROW THERAPEUTIC WINDOW) ADRs: Gastrointestinal, cardiac and neurological manifestations Arrhythmias Atrial tachycardia Hypokalemia- induced arrhythmias Blurred vision Severe toxicity produce seizures  3. Drugs that increase myocardial contraction CARDIAC GLYCOSIDES DIGOXIN orally or IV Pharmacokinetics Elimination is mainly by renal excretion and involves P-glycoprotein Half-time is approximately 36 h A loading dose is used in urgent situations. The therapeutic range is rather narrow (1–2.6 nmol/l). 3. Drugs that increase myocardial contraction CARDIAC GLYCOSIDES DIGOXIN Interactions Diltiazem, Verapamil and Quinidine reduce digoxin clearance and increase serum digoxin levels by inhibiting P-glycoprotein (increase the toxicity of digoxin) 3. Drugs that increase myocardial contraction CARDIAC GLYCOSIDES DIGOXIN Clinical uses Rapid persistent atrial fibrillation Treatment of heart failure in patients who remain symptomatic despite optimal use of diuretics and ACEIs 3. Drugs that increase myocardial contraction Mechanism of action: OTHER IONOTROPIC DRUGS increase cellular [AMPc] DOBUTAMINE (β1-adrenoceptor agonists) Used to treat acute but potentially reversible heart failure Produces less tachycardia than other β 1 agonists Used IV for short-term treatment of acute heart failure, cardiogenic shock or for pharmacological cardiac stress testing and echocardiography. MILRINONE (inhibitor of the heart-specific subtype type III-PD) Short-term management of heart failure in patients who are not responsive to other drugs. Inotropic support of infants and children awaiting cardiac transplantation 3. Drugs that increase myocardial contraction 3. Drugs that increase myocardial contraction OTHER IONOTROPIC DRUGS OMECAMTIV Selective cardiac myosin activator that lowers the risk of hospital admissions in patients who have heart failure with reduced left ventricular ejection fraction. MAVACAMTEN is a cardiac myosin inhibitor that decreases the excess contraction of heart muscles in patients with hypertrophic cardiomyopathy and currently under study