上游充通大淫 SHANGHAI JIAO TONG UNIVERSITY 1896 1920 1987 2006 Mechanism of Action of ACEI Afterload reduction Preload reduction Reduction of facilitation of sympathetic nervous system o Reduction of cardiac hypertrophy Drugs of choice in heart failure(with diuretics) Current investigational use:Acute myocardial infarction
Mechanism of Action Mechanism of Action of ACEI of ACEI Afterload reduction Preload reduction Reduction of facilitation of sympathetic nervous system Reduction of cardiac hypertrophy Drugs of choice in heart failure (with diuretics) Current investigational use: Acute myocardial infarction
上游充通大淫 SHANGHAI JIAO TONG UNIVERSITY 1896 1920 1987 2006 Aldosterone antagonist Spironolactone Aldosterone antagonist,K-sparing diuretic Prevention of aldosterone effects on: Kidney -Heart? ● Aldosterone inappropriately elevated in CHF Mobilizes edema fluid in heart failure ● Prevention of hypokalemia induced by loop diuretics(protection against digitalis toxicity?) Prolongs life in CHF patients
Aldosterone antagonist Aldosterone antagonist Aldosterone antagonist, K-sparing diuretic Prevention of aldosterone effects on: – Kidney – Heart? Aldosterone inappropriately elevated in CHF Mobilizes edema fluid in heart failure Prevention of hypokalemia induced by loop diuretics (protection against digitalis toxicity?) Prolongs life in CHF patients Spironolactone Spironolactone
上游充通大 SHANGHAI JIAO TONG UNIVERSITY 1896 1920 1987 2006 Section 2:Diuretics Mechanism of Action in Heart Failure Preload reduction:reduction of excess plasma volume and edema fluid Afterload reduction:lowered blood pressure IAO TONG
Section 2: Diuretics Section 2: Diuretics Preload reduction: reduction of excess plasma volume and edema fluid Afterload reduction: lowered blood pressure Mechanism of Action in Heart Failure Mechanism of Action in Heart Failure hydrochlorothiazide
上游充通大 SHANGHAI JIAO TONG UNIVERSITY 1896 1920 1987 2006 Section 3 B-Adrenoceptor blockers Mechanism of action: 1.Antagonize the sympathetic nerve activity ①↓damage on cardiac muscle from CA ②↓renin,↓RAS,↓cardiac load ③↑B-R,come back the transmit ability ④↑sensitivity ofβ-R to catecholamines 2.Antioxidation blocking a-R carvedilol NC UN 3.Antiarrhythmia and improve myocardial ischemia
Section 3 Section 3 β-Adrenoceptor blockers Adrenoceptor blockers Mechanism of action: 1. Antagonize the sympathetic nerve activity ①↓damage on cardiac muscle from CA ②↓renin , ↓RAS，↓ cardiac load ③↑β-R，come back the transmit ability ④↑sensitivity of β-R to catecholamines 2. Antioxidation , blocking α1 -R — carvedilol 3. Antiarrhythmia and improve myocardial ischemia
arvedilol or Metoprolol uropou 2006 Trial (COMET) 1511 patients receive carvedilol (25 mg BID); 1518 receive metoprolol (50 mg BID) NYHA II-IV;EF<.35;ACE-I+ diuretic (if tolerated) Mean 58 months in trial Carvedilol reduced all- cause (HR.83)and CV(.80) mortality relative to meto Poole-Wilson.Lancet 2003:362:7-13
Carvedilol or Metoprolol European Carvedilol or Metoprolol European Trial (COMET) Trial (COMET) 1511 patients receive carvedilol (25 mg BID); 1518 receive metoprolol (50 mg BID) NYHA II-IV; EF<.35; ACE-I + diuretic (if tolerated) Mean 58 months in trial Carvedilol reduced allcause (HR .83) and CV (.80) mortality relative to meto 0 10 20 30 40 All CV Car Met % Poole-Wilson. Lancet 2003;362:7-13 Deaths Deaths