1. ANTIHYPERTENSIVE Rx MED PHARM 2010

3. CARDIOVASCULAR DISEASE (CVD) Leading cause of death in the US 36% of deaths, 900,000 per year 52% due to coronary heart disease Mortality declining due to improved Dx & treatment

4. CVD & Severe Mental Illness Severe mental illness: 5-10% of population Loss of life expectancy: 25 years Due to premature CVD, not suicide

5. Lenfant C. N Engl J Med 2003;349:868-874 Change in U.S. Life Expectancy between 1970 and 2000

7. Messerli F. N Engl J Med 1995;332:1038-1039 Headlines of the St Louis Post-Dispatch April 13,1945

8. Messerli F. N Engl J Med 1995;332:1038-1039 Diastolic and Systolic Arterial Pressure of Franklin D. Roosevelt

10. Chobanian A. N Engl J Med 2009;361:878-887 Risk Factors for Hypertension

13. Adrogue H and Madias N. N Engl J Med 2007;356:1966-1978 Interaction of the Modern Western Diet and the Kidneys in the Pathogenesis of Primary Hypertension

14. Adrogue H and Madias N. N Engl J Med 2007;356:1966-1978 Molecular Pathways Implicated in the Generation of Increased Arterial and Arteriolar Smooth- Muscle Tone by an Excess of Sodium and a Deficit of Potassium in Primary Hypertension

15. DRUGS FOR HYPERTENSION DIURETICSDIRECT VASODILATORS Thiazide – Type Hydralazine Hydrochlorothiazide Minoxidil Chlorthalidone Nitroprusside LOOPCENTRAL ALPHA-ADRENERGIC FurosemideAGONISTS Clonidine POTASSIUM – SPARING TriamtereneCALCIUM CHANNEL BLOCKERS Verapamil Diltiazem Amlodopine

16. DRUGS FOR HYPERTENSION ALPHA-ADRENERGICBETA-ADRENERGICBLOCKERS Prazosin Propranolol Metoprolol ALPHA –BETA BLOCKERS ANGIOTENSIN RECEPTOR CarvedilolANTAGONISTS Labetalol Losartan ACE-Inhibitors RENIN ANTAGONISTS Benazepril Aliskiren

17. DIURETICS for HYPERTENSION Chlorthalidone Hydrochlorthiazide ADVERSE EFFECTS Fluid & electrolyte imbalance Hypokalemia Dysglycemia

18. Ernst M and Moser M. N Engl J Med 2009;361:2153-2164 Sites of Diuretic Action in the Nephron

21. Ernst M and Moser M. N Engl J Med 2009;361:2153-2164 aPotential Complications of DiureticAAAAs nd Their Associated Mechanisms

23. Landry D and Oliver J. N Engl J Med 2001;345:588-595 Regulation of Vascular Smooth-Muscle Tone

24. CENTRALLY ACTING ANTIHYPERTENSIVE DRUGS CLONIDINE

25. Central    agonist Hemodynamics Decrease in : Cardiac output Systemic vascular resistance

26. ALPHA- ADRENERGIC ANTAGONISTS PRAZOSIN Hemodynamics Decrease in systemic vascular resistance ADVERSE RESPONSE first dose hypotension

27. BETA ADRENERGIC ANTAGONISTS Propranolol non-selective Metoprolol cardioselective,   block Beta blockers are not as effective as the other 4 classes of drugs in reducing stroke, particularly in the elderly

29. BETA BOCKERS – ADVERSE EFFECTS CNS Cardiovascular Bad dreams Aggravation of severe CHF Depression Aggravation of occlusive arterial disease Slow A-V conduction Pulmonary Bronchospasm in Asthmatics Drug interactions Drugs that impair A-V conduction (digoxin and some calcium channel blockers)

30. VASODILATORS FOR HYPERTENSION HYDRALAZINE MINOXIDIL SODIUM NITROPRUSSIDE

31. HYDRALAZINE A direct acting vasodilator May prevent oxidation of NO Hemodynamics- Decrease in systemic vascular resistance

32. HYDRALAZINE Adverse Effects Fluid retention Lupus-like syndrome in slow acetylators Reflex tachycardia

33. MINOXIDIL ACTION: HEMODYNAMIC ACTIONS: ADVERSE EFFECTS: Direct acting peripheral vasodilator for resistant hypertension Decrease in systemic vascular resistance Fluid retention, Tachycardia, Angina, Pericardial effusion, Hirsutism, EKG changes

36. Griffiths, M. J.D. et al. N Engl J Med 2005;353:2683-2695 Regulation of the Relaxation of Vascular Smooth Muscle by Nitric Oxide

37. Landry D and Oliver J. N Engl J Med 2001;345:588-595 Regulation of Vascular Smooth-Muscle Tone

38. SODIUM NITROPRUSSIDE ACTION Direct relaxation of all vascular smooth muscle Balanced arteriolar and venous dilation Decrease in systemic vascular resistance Intravenous administration USES Hypertensive crisis Heart failure

39. Murad F. N Engl J Med 2006;355:2003-2011 Endothelium-Dependent Relaxation of Smooth Muscle

40. Murad F. N Engl J Med 2006;355:2003-2011 Cellular Signaling with Nitric Oxide and Cyclic GMP

41. RAAS ANGIOTENSIN II FORMATION

42. A II ACTIONS

43. Oparil, S. et. al. Ann Intern Med 2003;139:761-776 The angiotension II types 1 (AT 1 ) and 2 (AT 2 ) receptors have generally opposing effects

44. Goodfriend, T. L. et al. N Engl J Med 1996;334:1649-1655 Actions of Angiotensin II

45. BENAZEPRIL A Long-acting Inhibitor of Angiotensin Converting Enzyme

47. BENAZEPRIL ACTION: HEMODYNAMIC EFFECT: ADVERSE EFFECTS: Inhibits angiotensin converting enzyme, to reduce formation of angiotensin II and aldosterone, inhibits lysis of bradykinin, may alter prostaglandin metabolism and sympathetic transmission. Decreases total peripheral resistance Heart rate and cardiac output unchanged Cough, angioedema, teratogenic, neutropenia, agranulocytosis, loss of taste, skin rash,& hypotension

48. ACEI & ARB TERATOGENICITY 1st half ~2.7X increase in malformations CV & CNS 2 nd half oligohydramnios growth retardation pulmonary hypoplasia renal failure hypotension death

49. :

50. ANGIOTENSIN RECEPTOR ANTAGONISTS ( ARBs) LOSARTAN OTHERS

51. Goodfriend T et al. N Engl J Med 1996;334:1649-1655 Signal Transduction by Angiotensin AT1 Receptors

52. Oparil, S. et. al. Ann Intern Med 2003;139:761-776 The angiotension II types 1 (AT 1 ) and 2 (AT 2 ) receptors have generally opposing effects

53. RAAS RENIN ANTAGONIST ANGIOTENSIN II FORMATION

54. ALISKIREN Renin inhibitor Lowers blood pressure Outcome studies-none

55. CALCIUM CHANNEL BLOCKERS Verapamil Diltiazem Amlododipine

59. CALCIUM CHANNEL BLOCKERS ON THE HEART

60. CALCIUM CHANNEL ANTAGONISTS ADVERSE EFFECTS HypotensionHeart failure HeadacheAV Block ConstipationPeripheral edema DRUG INTERACTIONS: Digoxin or Beta blockers to cause A-V block

62. Chobanian A. N Engl J Med 2009;361:878-887 Advances in the Treatment of Hypertension

63. Chobanian A. N Engl J Med 2009;361:878-887 Changes in the Prevalence and Control of Hypertension in the United States (1988-2004)

64. Chobanian A. N Engl J Med 2009;361:878-887 Rates of Awareness, Treatment, and Control of High Blood Pressure in the United States (1976- 2004)

65. Chobanian A. N Engl J Med 2009;361:878-887 Comparative Drug Trials in Patients with Hypertension

66. HYPERTENSION & CV DISEASE Hypertension: Increased risk SCD & LVH 3X Risk increases with sbp Independently predisposes to CAD Increases risk of silent MI 63% of coronary events occur in: HTN+ at least 2 other risk factors

67. ANTIHYPERTENSIVE THERAPY FIRST-LINE DRUGS DIURETICS: THIAZIDE or THIAZIDE TYPE ACE INHIBITOR : LONG ACTING ARB : CCB : LONG ACTING BETA BLOCKERS : NO, absent a compelling indication ( Post - MI, HF,angina)

69. Algorithm for Management of Hypertension