1、Chapter 26Anti-congestive heart failure drugsLNMU PharmacologyChronic or Congestive Heart Failure，CHFCHF occurs when the cardiac output is inadequate to provide the oxygen needed by the body. The key defect in CHF is a decrease in cardiac contractility, resulting in inadequate cardiac outputThe Caus
2、es of Heart Failure Population-attributable risk,%010203040506070Male Female60393410 11586 4475Hyper- Myo- Angina Diabetes LV heart Valvulartension cardial hyper- heartinfarction trophy diseaseThe characterizations of CHFDecrease in cardiac contractility, inadequate cardiac output.Intravascular volu
3、me expansion and ventricular filling pressures, systemic and pulmonary hypertentension, dyspnea 呼吸困难.Activation of sympathetic nervous and RASMyocardial dysfunction.Ventricular remodeling.Ventricular remodeling after acute infarctionVentricular remodeling in diastolic舒张 and systolic收缩 heart failureI
4、nitial infarct Expansion of infarct(hours to days) Global remodeling(days to months)Normal heart Hypertrophied heart(diastolic heart failure) Dilated heart(systolic heart failure)Myocardial remodeling in Calcineurin transgenic hearts(Cell, Vol 93, 215-228,1998)Heart failureReduced cardiac outputSymp
5、athetic nervoussystem activationVasoconstriction Elevated cardiac filling pressureSodium and water retentionAngiotensin ReninCardiac remodelingAldosteroneAngiotensinPathophysiological mechanisms of heart failure and major sites of drug actiondigoxin -blockers, digoxinVasodilatorsACE inhibitorsAngiot
6、ensin-R blockersDiureticsSpironolactoneClassification of drugs used in CHF1. Renin-angiotensin-aldosterone system inhibitors (1) ACEI captopril(2) ang receptor blocker (AT 1 antagonist) losartan(3) aldosterone antagonist spironolacton2. Diuretics thiazides, furosemide3. -receptor blocker Metoprolol, carvedilol4. positive inotropic agents(1)Cardiac glycosides digoxin, digitoxin(2)non-glycoside positive inotropic agents milrinone5.vasodilators nitroprusside sodium6.calcium sensitizer and calcium channel blockers amlodipineSection IIInhibitors of renin-angiotensin-aldosterone system (RAAS)
