1. Anti-hypertensive Therapy

2. Introduction 50 million Americans age 6 and older have hypertension 90% suffer for primary (essential) hypertension People with lower educational and income levels

3. Diagnosis Repeated, reproducible and high BP measurements Not patient symptoms!

4. Hypertension Treatment Lifestyle Modifications Drug Therapy Substitute Drugs from different classes of anti-hypertensives

5. Hypertension Treatment Lifestyle Modifications Lifestyle Modifications Lose weight Reduce alcohol intake Reduce Na+ intake Reduce fat and cholesterol intake DASH diet Exercise Stop smoking

7. Hypertension Treatment Drug Therapy Overview If lifestyle modifications do not work, initiate Drug Therapy!

8. Drug Classifications 1. Diuretics 2. Calcium Channel Blockers 3. Sympatholytic Drugs 4. Vasodilators 5. ACE inhibitors 6. Angiotensin II antagonists

9. 1. Diuretics General Information Reduces pressure by 10-15 mmHg Can be combined with other anti- hypertensives May be used with potassium supplements Not useful in patients with renal insufficiency Mechanism of Action Na+ depletion Blood volume reduction Decreases peripheral resistance

10. 1.Diuretics Classes A. Thiazides B. Loop Diuretics C. Potassium-Sparing Diuretics

11. 1A.Diuretics Thiazides Used in patients with: mild to moderate HTN Normal cardiac and renal function Most frequently used anti-hypertensive in the USA Hydrochlorothiazide (Hydrodiuril) Chlorthalidone (Hygroton)

12. 1A. Diuretics Thiazides Side Effects Hypokalemia impaired diabetes control Hyperuricemia muscle cramps increased LDL/HDL ratio Contraindications Digitalis Lithium NSAIDS

13. 1B. Diuretics Loop Diuretics Shorter duration of action Subjects refractory to thiazides Furosemide (Lasix)

14. 1B. Diuretics Loop Diuretics Side Effects Dehydration Hypokalemia Impaired diabetes control Increases LDL/HDL ratio Contraindications Digitalis Lithium

15. 1C. Diuretics Potassium-Sparing Diuretics Used in combination with other diuretics Used to correct hypokalemia Used to avoid potassium depletion in digitalis patients Spironolactone (Aldactone) Aldosterone Antagonist Triamterene (Dyrenium)

16. 1C. Diuretics Potassium-Sparing Diuretics Side Effects Hyperkalemia Gynecomastia G.I. disturbances Contraindications Lithium NSAIDS ACE Inhibitors

17. 2.Calcium Channel Blockers

18. 2. Calcium Channel Blockers General Information Rarely associated with abnormalities in electrolyte, carbohydrate, or lipid metabolism Useful in ischemic heart disease, chronic pulmonary disease, diabetes mellitis, and variant angina Do not alter plasma levels of uric acid

19. 2.Calcium Channel Blockers Mechanism of Action Inhibit Ca++ influx into VSM Relax peripheral arteriole SM Decrease Peripheral resistance Interferes with Ang II and Alpha-2 mediated vasoconstriction

20. 2.Calcium Channel Blockers Drugs Nifedipine (Procardia) Dihydropyridine Selective vasodilator Less effect on heart Diltiazem (Cardizem) Heart and Vessels Verapamil (Calan) Mainly Heart

21. 2.Calcium Channel Blockers Side Effects Tachycardia Dizziness Edema Constipation Bradycardia Headache

22. 3.Sympatholytic Drugs General Information Reduce sympathetic activity to heart and blood vessels Must withdraw slowly Several classes

23. 3.Sympatholytic Drugs Classes A. Centrally acting agents B. Adrenergic blocking agents C. Alpha Antagonists D. Beta Antagonists

24. 3A.Sympatholytic Drugs Centrally acting agents Reduce sympathetic output from vasopressor centers in brainstem Decreases CO Decreases peripheral resistance Clonidine (Catapres) Methyldopa (Aldomet)

25. 3A.Sympatholytic Drugs Centrally acting agents: Clonidine Alpha-2 agonist at medullary cardiovascular centers Decreases sympathetic outflow from CNS Tablet and transdermal patch (reduced side effects?) Little effect on plasma proteins Side Effects Sedation Dry mouth Bradycardia (rare) Contraindications Other CNS depressants

26. 3A.Sympatholytic Drugs Centrally acting agents: Methyldopa Methyldopa Converted to Methyldopamine Converted to Methylnorepinephrine H3C-NE acts on central alpha-2 receptors Sympathetic outflow from CNS is decreased Blood pressure is decreased

27. 3A.Sympatholytic Drugs Centrally acting agents: Methyldopa Drug of choice for pre-eclampsia Side Effects Sedation Nightmares Movement Disorders Hyperprolactinemia Hypersensitivity of skin and liver (very rare) Anemia Contraindications MAOis Levodopa

28. 3B.Sympatholytic Drugs Adrenergic Blocking Agents: General Information Mechanism of Action Reduces NE release in heart and blood vessels Decrease CO and peripheral resistance Reserpine (Serpasil) Guanethidine (Ismelin)

29. 3B. Sympatholytic Drugs Adrenergic Blocking Agents: Reserpine Disrupts NE vesicular storage Both central and peripheral action Used to treat mild- moderate HTN Side Effects Sedation Diarrhea Depression Bradycardia Nasal Congestion Contraindications CNS depressants MAOis

30. 3B. Sympatholytic Drugs Adrenergic Blocking Agents: Guanethidine Prevents NE release from nerve terminals Effective, but side effects are severe Reserved for severe HTN Does not cross CNS Side Effects Orthostatic hypotension Diarrhea Bradycardia Impotence Contraindications TCAs

31. 3C. Sympatholytic Drugs Alpha Antagonists: General Information Mechanism of Action Act at post-synaptic receptors to produce arteriole and venous vasodilatation Decrease BP to a certain extent Does not impair exercise tolerance Prazosin (Minipress)

32. Less tachycardia Side Effects Dizziness Headaches Weakness Decrease LDL/HDL 3C. Sympatholytic Drugs Alpha Antagonists: Prazosin

33. 3D.Sympatholytic Drugs Beta Antagonists: General Information Mechanisms of Action Decrease contractility and CO Decrease renin secretion Decrease Ang II Must be withdrawn gradually May mask insulin- induced hypoglycemia 1) Propanolol (Inderal) 2) Nadolol (Corgard) 3) Pindolol (Visken) 4) Metoprolol (Lopressor) 5) Labetolol (Trandate, Normodyne)

34. Nonselective Beta antagonist Mild to moderate HTN Used with vasodilators Prevent tachycardia 3D.Sympatholytic Drugs Beta Antagonists: Propranolol

35. Nonselective Beta antagonist Long half-life Better patient compliance 3D.Sympatholytic Drugs Beta Antagonists: Nadolol

36. Nonselective Beta antagonist Partial agonist properties Less bradycardia 3D.Sympatholytic Drugs Beta Antagonists: Pindolol

37. Selective beta-1 antagonist 3D.Sympatholytic Drugs Beta Antagonists: Metoprolol

38. High incidence of side effects Sexual dysfunction Hypotension Useful in treatment of pheochromocytoma 3D.Sympatholytic Drugs Beta Antagonists: Labetolol

39. Mild-chronic fatique Low exercise tolerance Sedation Nightmares Increased airway resistance Bradycardia 3D.Sympatholytic Drugs Beta Antagonists: General Side Effects

40. 4.Vasodilators General Information Mechanism of Action Dilate small arteries Decrease peripheral resistance 1) Hydralazine (Apresoline) 2) Minoxidil (Loniten) 3) Nitroprusside (Nipride) 4) Diazoxide (Hyperstat IV)

41. 4.Vasodilators Hydralazine Orally effective Emergencies Normal hypertensive situations Mechanism: Increases cGMP K channel opener Side Effects Tachycardia Aggravation of Angina Fluid retention Nausea Sweating Flushing Lupus-like syndrome

42. 4.Vasodilators Minoxidil Resistant HTN Mechanism: Increases cGMP K channel opener Side Effects Tachycardia Aggravation of Angina Fluid Retention Nausea Sweating Flushing Hypertrichosis

43. 4.Vasodilators Nitroprusside Emergencies Immediate onset Short duration Side Effects Nausea Cyanide toxicity Muscle twitching

44. 4.Vasodilators Diazoxide Emergencies Long duration of action Mechanism: K channel opener Side Effects Severe tachycardia Prolonged hypotension Nausea

45. 5.ACE Inhibitors General Information Mechanism of Action Inhibits production of Ang II Decreases peripheral resistance Contraindicated in 2 nd and 3 rd trimesters of pregnancy

46. 5.ACE Inhibitors Drugs Drugs Captopril (Capoten) Enalapril (Vasotec) Lisinopril (Zestril, Prinvol) Side Effects Hyperkalemia Rash Dry cough Angioneurotic edema

47. 6.Angiotensin II Antagonists General Information Relax smooth muscle Increase salt and water excretion Decrease plasma volume Drugs Saralasin Losartan (Cozaar) Side Effects Hyperkalemia Contraindicated in 2 nd and 3 rd trimesters of pregnancy

48. Considerations Pregnancy African Americans Elderly Diabetes Mellitus Hyperlipidemia COPD

49. Considerations Pregnancy If taken before pregnancy, most anti- hypertensives can be continued Methyldopa is most widely used Beta-blockers, ACE Inhibitors, and Angiotensin II Antagonists are not recommended

50. Considerations African Americans 1 st Choice: Diuretics Decrease M & M Calcium channel blockers and alpha and beta blockers are effective Combination therapy may be the best answer

51. Considerations Elderly Smaller doses Closely monitor side effects

52. Considerations Diabetes Mellitus ACE Inhibitors, Alpha blockers, and Calcium Channel blockers are effective Possibly, because they have little effect on carbohydrate metabolism

53. Considerations Hyperlipidemia Diuretics have little effect on cholesterol and triglycerides Alpha blockers decrease LDL/HDL ratio Calcium channel blockers, ACE inhibitors, and Angiotensin II antagonists have little effect on lipid profile

54. Considerations COPD Avoid Beta blockers

55. Thank You Questions?