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Vasodilator Lecture

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Vasodilator Lecture

Vasodilator Lecture

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  • Transcript

    • 1. Drugs Used In the Treatment of Congestive Heart Failure(Cont)
    • 2.  
    • 3.  BLOCKERS AT 1 BLOCKERS
    • 4. DETERMINANTS OF VENTRICULAR FUNCTION STROKE VOLUME PRELOAD CONTRACTILITY CARDIAC OUTPUT HEART RATE AFTERLOAD - Synergistic LV contraction - LV wall integrity - Valvular competence
    • 5.  
    • 6.  
    • 7.  
    • 8.  
    • 9. Venous Vasodilatation MIXED  -adrenergic Blockers ACEI Angiotensin II inhibitors K + channel activators Nitroprusside VENOUS Nitrates Molsidomine ARTERIAL Minoxidil Hydralazin VASODILATORS CLASSIFICATION Arterial Vasodilatation
    • 10. 1- VENOUS VASODILATATION Preload 2- Coronary vasodilatation Myocardial perfusion 3- Arterial vasodilatation Afterload 4- Others Pulmonary congestion Ventricular size Vent. Wall stress MVO 2 NITRATES HEMODYNAMIC EFFECTS • Cardiac output • Blood pressure
    • 11.  
    • 12.  
    • 13. Placebo Enalapril 12 11 10 9 8 7 6 5 PROBABILITY OF DEATH MONTHS 0.1 0.8 0 0.2 0.3 0.7 0.4 0.5 0.6 p< 0.001 p< 0.002 CONSENSUS N Engl J Med 1987;316:1429 ACEI SURVIVAL 4 3 2 1 0
    • 14. VASOCONSTRICTION VASODILATATION Kininogen Kallikrein Inactive Fragments Angiotensinogen Angiotensin I RENIN Kininase II Inhibitor ALDOSTERONE SYMPATHETIC VASOPRESSIN PROSTAGLANDINS tPA ANGIOTENSIN II BRADYKININ ACEI MECHANISM OF ACTION A.C.E.
    • 15. ACEI HEMODYNAMIC EFFECTS Arteriovenous Vasodilatation - PCWP and LVEDP - SVR and BP - CO and exercise tolerance No change in HR / contractility MVO 2 Renal, coronary and cerebral flow Diuresis and natriuresis
    • 16. ACEI ADVANTAGES
      • Inhibit LV remodeling post-MI
      • Modify the progression of chronic CHF
        • - Survival
        • - Hospitalizations
        • - Improve the quality of life
      • In contrast to others vasodilators, do not produce neurohormonal activation or reflex tachycardia
      • Tolerance to its effects does not develop
    • 17. ACEI UNDESIRABLE EFFECTS Inherent in their mechanism of action - Hypotension - Hyperkalemia - Angioneurotic edema Due to their chemical structure - Cutaneous eruptions - Neutropenia, thrombocytopenia - Digestive upset - Dry cough - Renal Insuff. - Dysgeusia - Proteinuria
    • 18. ANGIOTENSIN II INHIBITORS MECHANISM OF ACTION RENIN Angiotensinogen Angiotensin I ANGIOTENSIN II ACE Other paths Vasoconstriction Proliferative Action Vasodilatation Antiproliferative Action AT1 AT2 AT1 RECEPTOR BLOCKERS RECEPTORS
    • 19. AT1 RECEPTOR BLOCKERS DRUGS Losartan Valsartan Irbersartan Candesartan Competitive and selective blocking of AT1 receptors
    • 20. 0.6 PROBABILITY OF DEATH 0 Placebo (273) Prazosin (183) Hz + ISDN (186) MONTHS 0.7 0.5 0.3 0.4 0.2 0.1 VHefT-1 N Engl J Med 1986;314:1547 NITRATES SURVIVAL 0 6 12 18 24 30 36 42
    • 21.  
    • 22.  
    • 23.
      • CARDIAC GLYCOSIDES
      • SYMPATHOMIMETICS
        • Catecholamines
        • ß-adrenergic agonists
      • PHOSPHODIESTERASE INHIBITORS
        • Amrinone
        • Enoximone
      • Others
      Milrinone Piroximone POSITIVE INOTROPES
    • 24.  
    • 25.  
    • 26. Inamrine&Mirinone
    • 27. 3. Nesiritide:  natriuretic peptide a. New treatment for acute congestive heart failure and dyspnea at rest
    • 28.  
    • 29.  
    • 30.  
    • 31.  
    • 32.  
    • 33. ß-ADRENERGIC BLOCKERS INDICATIONS and UTILIZATION Not clearly established Begin with very low doses Slow augmentation of dose Slow withdrawal ?
    • 34. ß-ADRENERGIC BLOCKERS POSSIBLE BENEFICIAL EFFECTS  Density of ß 1 receptors Inhibit cardiotoxicity of catecholamines  Neurohormonal  activation  HR Antihypertensive and antianginal Antiarrhythmic Antioxidant Antiproliferative
    • 35. ALDOSTERONE Retention Na + Retention H 2 O Excretion K + Excretion Mg 2+ Collagen deposition Fibrosis - myocardium - vessels Spironolactone Edema Arrhythmias Competitive antagonist of the aldosterone receptor (myocardium, arterial walls, kidney) ALDOSTERONE INHIBITORS
    • 36.  BLOCKERS AT 1 BLOCKERS

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