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ANTIHYPERTENSIVE Rx

ANTIHYPERTENSIVE Rx. MED PHARM 2010. Headlines of the St Louis Post-Dispatch April 13,1945. Messerli F. N Engl J Med 1995;332:1038-1039. Diastolic and Systolic Arterial Pressure of Franklin D. Roosevelt. Messerli F. N Engl J Med 1995;332:1038-1039. Risk Factors for Hypertension.

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ANTIHYPERTENSIVE Rx

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  1. ANTIHYPERTENSIVE Rx MED PHARM 2010

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

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

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

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

  6. 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 Adrogue H and Madias N. N Engl J Med 2007;356:1966-1978

  7. DRUGS FOR HYPERTENSION DIURETICS DIRECT VASODILATORS Thiazide – Type Hydralazine Hydrochlorothiazide Minoxidil Chlorthalidone Nitroprusside LOOP CENTRAL ALPHA-ADRENERGIC Furosemide AGONISTS Clonidine POTASSIUM – SPARING Triamterene CALCIUM CHANNEL BLOCKERS Verapamil Diltiazem Amlodopine

  8. DRUGS FOR HYPERTENSION ALPHA-ADRENERGIC BETA-ADRENERGIC BLOCKERS BLOCKERS Prazosin Propranolol Metoprolol ALPHA –BETA BLOCKERS ANGIOTENSIN RECEPTOR Carvedilol ANTAGONISTS Labetalol Losartan ACE-Inhibitors RENIN ANTAGONISTS Benazepril Aliskiren

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

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

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

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

  13. CENTRALLY ACTING ANTIHYPERTENSIVE DRUGS CLONIDINE

  14. CLONIDINE • Central a2 agonist • Hemodynamics Decrease in : Cardiac output Systemic vascular resistance

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

  16. BETA ADRENERGIC ANTAGONISTS • Propranolol non-selective • Metoprololcardioselective, b1 block Beta blockers are not as effective as the other 4 classes of drugs in reducing stroke, particularly in the elderly

  17. 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)

  18. VASODILATORS FOR HYPERTENSION HYDRALAZINE MINOXIDIL SODIUM NITROPRUSSIDE

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

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

  21. 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 MINOXIDIL

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

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

  24. 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

  25. RAAS ANGIOTENSIN II FORMATION

  26. A II ACTIONS

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

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

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

  30. 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 BENAZEPRIL

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

  32. :

  33. ANGIOTENSIN RECEPTOR ANTAGONISTS ( ARBs) LOSARTAN OTHERS

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

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

  36. RAASRENIN ANTAGONIST • ANGIOTENSIN II FORMATION

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

  38. CALCIUM CHANNEL BLOCKERS Verapamil Diltiazem Amlododipine

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