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Pharmacology of ACE inhibitors ARBs and CCBs Ed Sheridan, Pharm.D.
Pharmacology ACEi, ARBs, CCB ,[object Object],[object Object],[object Object],[object Object]
The Renin-Angiotensin System ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
The Renin-Angiotensin System ,[object Object],[object Object],[object Object],[object Object]
Angiotensin II Effects on the Kidney ,[object Object],[object Object],[object Object]
Liver Angiotensinogen Angiotensin I Angiotensin II Aldosterone Increased Blood Volume Increase BP Kidney Renin ACE Renin-Angiotensin System Increased TPR Increased CO Salt & Water Retension
ACE  Inhibitors Brand Generic Mavik Trandolapril Altace Ramipril Accupril Quinapril Aceon Perindopril Univasc Moexipril Prinivil Lisinopril Monopril Fosinopril Vasotec Enalapril Capoten Captopril Lotensin Benazepril
Not to be confused with those of you who voted Ace Young off  American Idol
ACEi Uses ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
MOA of ACE Inhibitors ,[object Object],[object Object],[object Object],[object Object],[object Object]
Angiotensinogen Angiotensin I Angiotensin II Vasoconstriction Increased peripheral vascular resistance Increased   blood pressure Aldosterone secretion Increased sodium and water retention Kininogen Bradykinin Inactive Increased prostaglandin synthesis Vasodilation Decreased peripheral vascular resistance Decreased  blood pressure Kalikrein Converting Enzyme 2 2 1 1 X Renin
Blocking the Renin-Angiotensin System ,[object Object],[object Object],[object Object],[object Object]
ACEi Efficacy ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
ACE Inhibitors- Side Effects ,[object Object],[object Object],[object Object],[object Object]
ACE Inhibitors- Side Effects ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],ACE Inhibitors- Comments
Angiotensin Receptor Blockers Brand Generic Diovan Valsartan Micardis Telmisartin Cozaar Losartan Avapro Irbesartan Atacand Candesartan
ARBs Uses ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Angiotensin Receptor Blockers: Mechanisms ,[object Object],[object Object],[object Object],[object Object],[object Object]
Angiotensinogen Angiotensin I Angiotensin II Vasoconstriction Increased peripheral vascular resistance Increased   blood pressure Aldosterone secretion Increased sodium and water retention Kininogen Bradykinin Inactive Increased prostaglandin synthesis Vasodilation Decreased peripheral vascular resistance Decreased  blood pressure Kalikrein Converting Enzyme 2 2 1 1 X X Renin
ARB Side effects ,[object Object],[object Object],[object Object],[object Object]
ARB Efficacy ,[object Object],[object Object],[object Object],[object Object],[object Object]
Calcium Channel Blockers ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Two groups ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Cardiac effects ,[object Object],[object Object],[object Object],[object Object],[object Object]
Vascular effects ,[object Object],[object Object],[object Object],[object Object],[object Object]
CCB Efficacy ,[object Object],[object Object],[object Object]
CCB Safety ,[object Object],[object Object],[object Object],[object Object]
Calcium Blockers Side effects ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Pharmacology ACEi, ARBs, CCB ,[object Object],[object Object],[object Object],[object Object]
Treatment of Hypertension ,[object Object],*BP=CO x PVR
Treatment of Hypertension ,[object Object],[object Object],[object Object]
Treatment of Hypertension Introduction ,[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],Hypertension Introduction
CVD Risk ,[object Object],[object Object],[object Object]
Blood Pressure Classification <80 and <120 Normal 80–89 or 120–139 Prehypertension 90–99 or 140–159 Stage 1 Hypertension > 100 or > 160 Stage 2 Hypertension DBP mmHg SBP mmHg BP Classification
Patient Evaluation ,[object Object],[object Object],[object Object],[object Object]
CVD Risk Factors ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],* Components of the metabolic syndrome .
Identifiable  Causes of Hypertension ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Target Organ Damage   ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Laboratory Tests ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Goals of Therapy ,[object Object],[object Object],[object Object]
Benefits of Lowering BP Average Percent Reduction Stroke incidence  35–40%  Myocardial infarction  20–25%  Heart failure 50%
Benefits of Lowering BP In stage 1 HTN and additional CVD risk factors, achieving  a sustained 12 mmHg reduction in SBP over 10 years will  prevent 1 death for every 11 patients treated.
BP Control Rates Trends in awareness, treatment, and control of high  blood pressure in adults ages 18–74 Sources:  Unpublished data for 1999–2000 computed by M. Wolz, National Heart, Lung, and Blood Institute; JNC 6 . 34 27 29 10 Control 59 54 55 31 Treatment 70 68 73 51 Awareness 1999–2000 II (Phase 2) 1991–94 II (Phase 1) 1988–91 II 1976–80 National Health and Nutrition Examination Survey, Percent
Treatment Overview ,[object Object],[object Object],[object Object],[object Object],[object Object]
Lifestyle Modification Approximate SBP reduction (range) Modification 5–20 mmHg/10 kg weight loss Weight reduction   8–14 mmHg Adopt DASH eating plan   2–8 mmHg Dietary sodium reduction   4–9 mmHg Physical activity  2–4 mmHg Moderation of alcohol consumption
DASH Fact Sheet
Review of Agents Pharmacology for Hypertension ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
 
Review of Important Aspects of Diuretics in the Treatment of Hypertension   ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Centrally Acting Drugs ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Adrenergic Neuron Blocking Agents ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Beta Receptor Blocking Agents ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Alpha Receptor Blockers ,[object Object],[object Object],[object Object]
Vasodilators ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Vasodilators ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Vasodilators ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Vasodilator ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Vasodilators ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
 
Algorithm for Treatment of Hypertension Not at Goal Blood Pressure (<140/90 mmHg)  (<130/80 mmHg for those with diabetes or chronic kidney disease ) Initial Drug Choices Lifestyle Modifications Drug(s) for the compelling indications  Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB)  as needed.   With Compelling  Indications Stage 2 Hypertension   (SBP  > 160 or DBP  > 100 m mHg)  2-drug combination for most (usually thiazide-type diuretic and  ACEI, or ARB, or BB, or CCB) Stage 1 Hypertension (SBP 140 –159 or DBP 90–99 mmHg)  Thiazide-type diuretics for most.  May consider ACEI, ARB, BB, CCB,  or combination. Without Compelling  Indications Not at Goal  Blood Pressure Optimize dosages or add additional drugs  until goal blood pressure is achieved. Consider consultation with hypertension specialist.
Classification and Management  of BP for adults * Treatment determined by highest BP category. † Initial combined therapy should be used cautiously in those at risk for orthostatic hypotension. ‡ Treat patients with chronic kidney disease or diabetes to BP goal of <130/80 mmHg.   Two-drug combination for most †  (usually thiazide-type diuretic and ACEI or ARB or BB or CCB).   Yes   > 100   > 160   Stage 2 Hypertension   Drug(s) for the compelling indications. ‡ Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed.  Thiazide-type diuretics for most.  May consider ACEI, ARB, BB, CCB, or combination.   Yes   90–99   140–159   Stage 1 Hypertension   Drug(s) for compelling indications.  ‡   No antihypertensive drug indicated.   Yes   80–89   120–139   Prehypertension   Encourage   <80   <120   Normal   With compelling indications Without compelling indication  Initial drug therapy   Lifestyle modification   DBP*  mmHg   SBP* mmHg   BP classification
Compelling Indications for Individual Drug Classes Clinical Trial Basis Initial Therapy Options   Compelling Indication   ALLHAT, HOPE, ANBP2, LIFE, CONVINCE   ACC/AHA Post-MI Guideline, BHAT, SAVE, Capricorn, EPHESUS ACC/AHA Heart Failure Guideline,   MERIT-HF, COPERNICUS, CIBIS, SOLVD, AIRE, TRACE, ValHEFT, RALES   THIAZ, BB, ACE, CCB   BB, ACEI, ALDO ANT   THIAZ, BB, ACEI, ARB, ALDO ANT   High CAD risk   Postmyocardial infarction   Heart failure
Compelling Indications for Individual Drug Classes Recurrent stroke prevention   Chronic kidney disease   Diabetes   Clinical Trial Basis Initial Therapy Options   Compelling Indication   PROGRESS   NKF Guideline, Captopril Trial, RENAAL, IDNT, REIN, AASK   NKF-ADA Guideline,   UKPDS, ALLHAT   THIAZ, ACEI   ACEI, ARB   THIAZ, BB, ACE, ARB, CCB
Special Considerations ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Minority Populations ,[object Object],[object Object],[object Object],[object Object],[object Object]
Left Ventricular Hypertrophy ,[object Object],[object Object]
Peripheral Arterial Disease (PAD) ,[object Object],[object Object],[object Object],[object Object]
Hypertension in Older Persons ,[object Object],[object Object],[object Object],[object Object]
Postural Hypotension ,[object Object],[object Object],[object Object]
Dementia ,[object Object],[object Object]
Hypertension in Women ,[object Object],[object Object],[object Object]
Children and Adolescents ,[object Object],[object Object],[object Object],[object Object]
Hypertensive Urgencies  and Emergencies ,[object Object],[object Object]
Additional Considerations in Antihypertensive Drug Choices ,[object Object],[object Object],[object Object],[object Object],[object Object]
Additional Considerations in Antihypertensive Drug Choices ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Followup and Monitoring ,[object Object],[object Object],[object Object],[object Object]
Followup and Monitoring (continued) ,[object Object],[object Object]
 
Improving Hypertension Control ,[object Object],[object Object]
Strategies for Improving  Adherence to Regimens ,[object Object],[object Object]
Causes of  Resistant Hypertension ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Treatment of Hypertension ,[object Object],[object Object],[object Object]
Abbreviated References ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

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Htn05

  • 1. Pharmacology of ACE inhibitors ARBs and CCBs Ed Sheridan, Pharm.D.
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  • 6. Liver Angiotensinogen Angiotensin I Angiotensin II Aldosterone Increased Blood Volume Increase BP Kidney Renin ACE Renin-Angiotensin System Increased TPR Increased CO Salt & Water Retension
  • 7. ACE Inhibitors Brand Generic Mavik Trandolapril Altace Ramipril Accupril Quinapril Aceon Perindopril Univasc Moexipril Prinivil Lisinopril Monopril Fosinopril Vasotec Enalapril Capoten Captopril Lotensin Benazepril
  • 8. Not to be confused with those of you who voted Ace Young off American Idol
  • 9.
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  • 11. Angiotensinogen Angiotensin I Angiotensin II Vasoconstriction Increased peripheral vascular resistance Increased blood pressure Aldosterone secretion Increased sodium and water retention Kininogen Bradykinin Inactive Increased prostaglandin synthesis Vasodilation Decreased peripheral vascular resistance Decreased blood pressure Kalikrein Converting Enzyme 2 2 1 1 X Renin
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  • 17. Angiotensin Receptor Blockers Brand Generic Diovan Valsartan Micardis Telmisartin Cozaar Losartan Avapro Irbesartan Atacand Candesartan
  • 18.
  • 19.
  • 20. Angiotensinogen Angiotensin I Angiotensin II Vasoconstriction Increased peripheral vascular resistance Increased blood pressure Aldosterone secretion Increased sodium and water retention Kininogen Bradykinin Inactive Increased prostaglandin synthesis Vasodilation Decreased peripheral vascular resistance Decreased blood pressure Kalikrein Converting Enzyme 2 2 1 1 X X Renin
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  • 36. Blood Pressure Classification <80 and <120 Normal 80–89 or 120–139 Prehypertension 90–99 or 140–159 Stage 1 Hypertension > 100 or > 160 Stage 2 Hypertension DBP mmHg SBP mmHg BP Classification
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  • 43. Benefits of Lowering BP Average Percent Reduction Stroke incidence 35–40% Myocardial infarction 20–25% Heart failure 50%
  • 44. Benefits of Lowering BP In stage 1 HTN and additional CVD risk factors, achieving a sustained 12 mmHg reduction in SBP over 10 years will prevent 1 death for every 11 patients treated.
  • 45. BP Control Rates Trends in awareness, treatment, and control of high blood pressure in adults ages 18–74 Sources: Unpublished data for 1999–2000 computed by M. Wolz, National Heart, Lung, and Blood Institute; JNC 6 . 34 27 29 10 Control 59 54 55 31 Treatment 70 68 73 51 Awareness 1999–2000 II (Phase 2) 1991–94 II (Phase 1) 1988–91 II 1976–80 National Health and Nutrition Examination Survey, Percent
  • 46.
  • 47. Lifestyle Modification Approximate SBP reduction (range) Modification 5–20 mmHg/10 kg weight loss Weight reduction 8–14 mmHg Adopt DASH eating plan 2–8 mmHg Dietary sodium reduction 4–9 mmHg Physical activity 2–4 mmHg Moderation of alcohol consumption
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  • 62. Algorithm for Treatment of Hypertension Not at Goal Blood Pressure (<140/90 mmHg) (<130/80 mmHg for those with diabetes or chronic kidney disease ) Initial Drug Choices Lifestyle Modifications Drug(s) for the compelling indications Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed. With Compelling Indications Stage 2 Hypertension (SBP > 160 or DBP > 100 m mHg) 2-drug combination for most (usually thiazide-type diuretic and ACEI, or ARB, or BB, or CCB) Stage 1 Hypertension (SBP 140 –159 or DBP 90–99 mmHg) Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination. Without Compelling Indications Not at Goal Blood Pressure Optimize dosages or add additional drugs until goal blood pressure is achieved. Consider consultation with hypertension specialist.
  • 63. Classification and Management of BP for adults * Treatment determined by highest BP category. † Initial combined therapy should be used cautiously in those at risk for orthostatic hypotension. ‡ Treat patients with chronic kidney disease or diabetes to BP goal of <130/80 mmHg. Two-drug combination for most † (usually thiazide-type diuretic and ACEI or ARB or BB or CCB). Yes > 100 > 160 Stage 2 Hypertension Drug(s) for the compelling indications. ‡ Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed. Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination. Yes 90–99 140–159 Stage 1 Hypertension Drug(s) for compelling indications. ‡ No antihypertensive drug indicated. Yes 80–89 120–139 Prehypertension Encourage <80 <120 Normal With compelling indications Without compelling indication Initial drug therapy Lifestyle modification DBP* mmHg SBP* mmHg BP classification
  • 64. Compelling Indications for Individual Drug Classes Clinical Trial Basis Initial Therapy Options Compelling Indication ALLHAT, HOPE, ANBP2, LIFE, CONVINCE ACC/AHA Post-MI Guideline, BHAT, SAVE, Capricorn, EPHESUS ACC/AHA Heart Failure Guideline, MERIT-HF, COPERNICUS, CIBIS, SOLVD, AIRE, TRACE, ValHEFT, RALES THIAZ, BB, ACE, CCB BB, ACEI, ALDO ANT THIAZ, BB, ACEI, ARB, ALDO ANT High CAD risk Postmyocardial infarction Heart failure
  • 65. Compelling Indications for Individual Drug Classes Recurrent stroke prevention Chronic kidney disease Diabetes Clinical Trial Basis Initial Therapy Options Compelling Indication PROGRESS NKF Guideline, Captopril Trial, RENAAL, IDNT, REIN, AASK NKF-ADA Guideline, UKPDS, ALLHAT THIAZ, ACEI ACEI, ARB THIAZ, BB, ACE, ARB, CCB
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