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Dr Abida Shaheen
Blood Pressure =     Cardiac Output X      Peripheral Resistance   Preload     Contractility                  Vasoconstric...
Afterload                                                              α2      Vasomotor center        Volume        Kidne...
Sites of action of antihypertensive drugs
Renin-Angiotensin-Aldosterone System  Angiotensinogen Renin    Angiotensin I ACE    Angiotensin II↑ Aldosterone    AT I   ...
Angiotensin Converting                 EnzymeKininogens                                     Angiotensinogen               ...
Angiotensin II
Pathophysiologic role of Angiotensin IIAngiotensin Receptor    Angiotensin IIBlocker             ARB                      ...
ACEIs : Prevention of renal disease           INTRAGLOMERULAR PRESSUREArterialpressure                 Angiotensin II     ...
Aldosterone Plays a Multi-factorial CV RoleAngiotensin II–K+ –ACTH- Norepinephrine – Serotonin – Endothelin-NO            ...
Neurohormonal Activation in       Heart FailureAngiotensin II                     Norepinephrine                 Disease P...
Effect of ACE Inhibition↑ Angiotensin II                     ↑ Norepinephrine      ACE inhibitor                   Disease...
Effect of β-Blockade↑ Angiotensin II                     ↑ Norepinephrine                                     β-Blockade  ...
Effect of ARB↑ Angiotensin II                     ↑ Norepinephrine       ACE Inhibitor                 β-Blockade         ...
Figure 11.7
Beta Blockers           Mechanisms of Action Effects on myocardiumSuppression of renin releaseInhibition of presynatic ...
Beta Blockers   Hypertension   Angina pectoris   Myocardial Infarction   Arrhythmias   Heart Failure   Conditions as...
Beta BlockersSide Effects     Bronchospasm     Bradicardia/heart block     Mask and prolong the symptoms of hypoglycemi...
Without Compelling                                     Indications           Stage 1 Hypertension                      Sta...
Classification of Heart Failure                  ACC/AHA HF Stage1                                       NYHA Functional C...
Stages of Heart Failure and Treatment Options for Systolic Heart FailureJessup, M. et al. N Engl J Med 2003;348:2007-2018
Therapies     Relative Risk   Mortality              Reduction       2 yearACE-I                 23%         27%Β-Blockers...
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  1. 1. Dr Abida Shaheen
  2. 2. Blood Pressure = Cardiac Output X Peripheral Resistance Preload Contractility Vasoconstriction Heart Rate Venous Arteriolar Venous CirculatingFluid Volume Renin Renal Sympathetic Vascular Angiotensin Sodium Nervous Smooth Aldosterone Handling System Muscle System Vascular remodeling
  3. 3. Afterload α2 Vasomotor center Volume Kidneys Cardiac Output β1 Heart Renin β1 V VAng I Preload Ang II BP= CO x TPVR β2 α1 Aldosterone VSMCs Vascular Resistance arterioles Capacitance venules Smooth Muscle Cells TPVR Total Peripheral Vascular Resistance (TPVR)
  4. 4. Sites of action of antihypertensive drugs
  5. 5. Renin-Angiotensin-Aldosterone System Angiotensinogen Renin Angiotensin I ACE Angiotensin II↑ Aldosterone AT I ATII Vasoconstriction ↑ Blood Pressure
  6. 6. Angiotensin Converting EnzymeKininogens Angiotensinogen Kallikrein Renin Angiotensin I Bradykinin ACEIs ACEIs ACE Angiotensin IIInactive Peptides BK receptors AT-1 receptors
  7. 7. Angiotensin II
  8. 8. Pathophysiologic role of Angiotensin IIAngiotensin Receptor Angiotensin IIBlocker ARB AT1 Aldosterone Vasoconstriction Receptor Production Cell Growth Fibrosis ↑ Sodium/Water ↑ PVR Retention LVH ↑ BP Vascular ↑ BP Remodeling
  9. 9. ACEIs : Prevention of renal disease INTRAGLOMERULAR PRESSUREArterialpressure Angiotensin II Angiotensin II + + ++Afferent 20 Efferent mmHgarteriole arteriole excess glomerular Bowman’s pressure capsule hyperfiltration microalbuminuria
  10. 10. Aldosterone Plays a Multi-factorial CV RoleAngiotensin II–K+ –ACTH- Norepinephrine – Serotonin – Endothelin-NO Aldosterone Kidneys Brain Blood Vessels Heart +SNS Na+ reabsorption ↑ Blood Cytokine Activation K+ excretion Pressure Vascular Inflammation Cardiac Hypertrophy Endothelial Dysfunction Myocardial fibrosis Hypertension Vascular Injury LV Hypertrophy Ventricular Remodeling End-stage renal disease, MI, HF, Arrhythmias
  11. 11. Neurohormonal Activation in Heart FailureAngiotensin II Norepinephrine Disease Progression Hypertrophy, apoptosis, ischemia, arrhythmias, remodeling, fibrosis
  12. 12. Effect of ACE Inhibition↑ Angiotensin II ↑ Norepinephrine ACE inhibitor Disease Progression Hypertrophy, apoptosis, ischemia, arrhythmias, remodeling, fibrosis
  13. 13. Effect of β-Blockade↑ Angiotensin II ↑ Norepinephrine β-Blockade Disease Progression Hypertrophy, apoptosis, ischemia, arrhythmias, remodeling, fibrosis
  14. 14. Effect of ARB↑ Angiotensin II ↑ Norepinephrine ACE Inhibitor β-Blockade ARB Disease Progression Hypertrophy, apoptosis, ischemia, arrhythmias, remodeling, fibrosis
  15. 15. Figure 11.7
  16. 16. Beta Blockers Mechanisms of Action Effects on myocardiumSuppression of renin releaseInhibition of presynatic β 1 receptors positivefeebackDecreased central sympathetic outflowCNS effectsReduction in peripheral resistanceImprovement in vascular complianceResetting of baroreceptor levelsAttenuation of pressor response to catecholamines(stress, exercise)
  17. 17. Beta Blockers Hypertension Angina pectoris Myocardial Infarction Arrhythmias Heart Failure Conditions associated with sympathetic overactivity Migraine prophylaxis Perioperative Hypertension
  18. 18. Beta BlockersSide Effects  Bronchospasm  Bradicardia/heart block  Mask and prolong the symptoms of hypoglycemia  Abrupt withdrawal can precipitate MI  Cold extremities, Raynaud’s phenomenon, intermittent claudication  Decreased exercise tolerance; fatigue, depression and impotence  CNS: sleep disturbance, vivid dreams, nightmares  Effects of plasma lipids
  19. 19. Without Compelling Indications Stage 1 Hypertension Stage 2 Hypertension (SBP 140–159 or DBP 90–99 (SBP >160 or DBP >100 mmHg) mmHg) 2-drug combination for most Thiazide-type diuretics for most. (usually thiazide-type diuretic and May consider ACEI, ARB, BB, CCB, ACEI, or ARB, or BB, or CCB) until goal blood pressure is achieved or combination.Optimize dosages or add additional dru Blood Pressure Not at Goal Initial Drug Choices Lifestyle Modifications as needed. (diuretics, ACEI, ARB, BB, CCB) Not at Goal Blood Pressure (<140/90 mmHg) Other antihypertensive drugs indications Drug(s) for the compelling (<130/80 mmHg for those with diabetes or chronic kidney disease) Indications With Compelling Algorithm for Treatment of Hypertension
  20. 20. Classification of Heart Failure ACC/AHA HF Stage1 NYHA Functional Class2A At high risk for heart failure but without structural heart disease or symptoms of heart failure (eg, patients with hypertension or coronary artery disease) I AsymptomaticB Structural heart disease but without symptoms of heart failure II Symptomatic with moderate exertionC Structural heart disease with prior or current symptoms of heart failure III Symptomatic with minimal exertionD Refractory heart failure requiring IV Symptomatic at rest specialized interventions1 Hunt SA et al. J Am Coll Cardiol. 2001;38:2101–2113.2 New York Heart Association/Little Brown and Company, 1964. Adapted from: Farrell MH et al. JAMA. 2002;287:890–897.
  21. 21. Stages of Heart Failure and Treatment Options for Systolic Heart FailureJessup, M. et al. N Engl J Med 2003;348:2007-2018
  22. 22. Therapies Relative Risk Mortality Reduction 2 yearACE-I 23% 27%Β-Blockers 35% 12%Aldosterone 30% 19%AntagonistsICD 31% 8.5%

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