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1、Pharmacological Management of Congestive Heart Failure,By De-chang Zhang Peking Union Medical College,EPIDEMIOLOGY OF CHF,Most common cause of hospitalization over 65 years of age. Afflicts more than 2 million Americans annually. 900,000 hospitalization per year.,PROGNOSIS,射血分数（Ejection Fraction，EF)
2、,一次心跳由一侧心室射出的血量称为每搏输出量(stroke volume, SV) 。每搏输出量占心室舒张末期容积的百分比称为射血分数（EF），在安静状态下，射血分数为55 65%。,Subtypes of CHF,Low output, diastolic dysfunction,Low output, systolic dysfunction,High-output failure,metabolic and oxygen demands, Contractility Heart size left ventricular end-diastolic volume EF stroke vo
3、lume CO,Hyperthyroidism, Beriberi(脚气病), anemia, arteriovenous shunts(动静脉分流).,HIGH-OUTPUT FAILURE,Characteristics,Contributingfactors,Biology,Glycosides are not effective in treating it.,contractility (cardiomyopathy) afterload (elevated SVR, systemic vascular resistance),Hypofunctioning left ventric
4、le; enlarged heart (dilated left ventricle); left ventricular end-diastolic volume; EF (40%); stroke volume; cardiac output；,Coronary ischemia. MI (myocardial infarction), Hypertension, aortic stenosis, volume overload,LOW-OUTPUT FAILURE （ systolic ）,Contributingfactors,Biology,Glycosides are effect
5、ive in treating it.,Characteristics,1.Thickened left ventricle (hypertrophic cardiomyopathy) 2. stiff left ventricle (restrictive cardiomyopathy左心室硬化) 3. preload,Normal ntractility; normal heart size; stiff left ventricle; left ventricular end-diastilic volume; normal EF; SV (stroke volume);,1. coro
6、nary ischemia, MI, hypertension， pericarditis, enlarged left ventricular septum 2. Amyloidosis 3. Sodium and water retention,LOW-OUTPUT FAILURE （ diastolic ）,Contributingfactors,Biology,30% to 40% of cases,Characteristics,CONSEQUENCES OF CHF,1.Subnormal Cardiac Output,2.Neurohumoral Reflexes,3.Myoca
7、rdial Hypertrophy,CHF makes the ventricular function cruve shift downward.,Ventricular Function Curve,TREATMENT OF CHF,Effect of ACEIs,Significantly decreased mortality due to CHF,ACTION:,Inhibit the activation of the renin-angiotensin system, which is hyperactive in CHF, due to increased sympatheti
8、cs. Reduce afterload: Reduce circulating levels of Angiotensin-II Reduce preload: Reduce Aldosterone - reduce blood volume,INDICATIONS:, All patients with symptomatic CHF due to LV systolic dysfunction. Asymptomatic patients with severe LV systolic dysfunction, HTN, or valvular regurgitation (aortic
9、 incompetence，mitral regurgitation).,Effect of enalapril on the mortality of patients with CHF,Goal in this case is to reduce blood volume, not reduce blood pressure.,LOOP DIURETICS:,Effect of -blockers on the mortality of patients with CHF,VASODILATORS：,Sodium Nitroprusside,Hydralazine,XANTHINES,Th
10、eophylline,used to treat acutely decompensated CHF, where brain and kidney perfusion is compromised,maintains renal blood flow. Used to treat CHF in the presence of kidney dysfunction,can produce coronary vasodilatation and bronchodilation, both of which can be therapeutic in CHF,Inotropic agents us
11、ed for CHF,CARDIAC GLYCOSIDES (DIGITALIS),Squill(海葱）埃及人古罗马人，水肿，强心，健体 Foxglove (1785) Strophanthus（毒毛旋花子，1890）,STRUCTURE: Steroid nucleus Aglycone(糖苷配基), responsible for biological activity Digitoxose sugar (洋地黄毒素糖)molecules. 3 sugar molecules, which affect absorption, half-life, and metabolism.,The
12、mechanism of cardiac muscle contraction,The mechanism of CARDIAC GLYCOSIDES,Mechanism,Ca+,Ca+,Na+,K+,ATP,ADP + Pi,Out,In,CARDIAC GLYCOSIDES,Na+,CARDIAC GLYCOSIDES (DIGITALIS): Inotropic agents used for CHF.,Pharmacological Effects:,ELECTRICAL ACTION on HEART,KIDNEY DIURESIS,Electrophysiologic Effect
13、,INDICATIONS of DIGITALIS,atrial fibrillation,CHF,paradoxical ventricular tachycardia,PHARMACOKINETICS OF DIGITALIS,IV Administration:,Ouabain(哇巴因） or Digoxin （地高辛）can be administered IV for emergencies. They are diluted with saline solution and injected slowly.,DIGITALIZATION:,Goal = attain the max
14、imum cardiac effects as quickly as possible, without producing toxicity. Loading doses can be given for Digoxin, to help attain the steady state faster. Must be careful to avoid arrhythmias when giving loading dose. Or, you can give smaller maintenance doses not preceded by a loading dose. 6-8 maint
15、enance doses per loading dose.,The half-life of the drug determines its duration of action:,Digoxin: Takes about 1 week to attain steady state, without a loading dose. Digitoxin: Takes about 3 to 4 weeks to attain steady state, without a loading dose.,PROPERTIES OF DIGIGALIS,TOXICITY OF DIGITALIS:,D
16、igitalis has a very narrow margin of safety RISK-FACTORS: 20% of patients will show toxicity,At-risk situations,Renal Insufficiency Geriatric Patients Excessive Dosing Hypokalemia as induced by diuretics fatal arrhythmias. Digitalis has additive effects in depleting cardiac cells of K+. Hypothyroidism: decreases the necessary dose.,ADVERSE EFFECTS OF DIGITALIS,
