1. HYPERTENSION BY: DR. MARWA SHAALAN PHARM-D

2. HTN = BP > 140/90 Assos. With: premature death vascular disease of brain, heart,kidneys HYPERTENSION

3. Goal of treatment Prolong useful life by preventing cardiovascular problems by reducing BP < 140/90

4. Types of Hypertension Primary HTN: also known as essential HTN. accounts for 95% cases of HTN. no universally established cause known. Secondary HTN: less common cause of HTN ( 5%). secondary to other potentially rectifiable causes.

5. Blood Pressure Primary Factors 1. Cardiac output 2. Peripheral resistance 3. Blood Volume

6. Initial tx. of hypertension Lifestyle modification first No smoking Weight control Reduce alcohol intake Decrease stress Sodium control

7. Treatment of hypertension Lifestyle modification first Initial tx. drug- diuretic or B-blocker Low dose first, increase dose if necessary 2 nd med. if needed Most respond with diuretic and one other medication (stepped care)

8. Drugs to treat hypertension 5 primary classes 1. Diuretics 2. Calcium channel blockers 3. Angiotesin converting enzyme (ACE) inhibitors 4. Autonomic nervous system agents 5. Direct acting vasodilators

9. 1- Diuretics Treats: mild to moderate HTN First drug of treatment of hypertension. Also treats heart failure or kidney disease Few adverse side effects Used with other anti-hypertensives to enhance effectiveness

10. Diuretics Action Reduce blood volume through urinary excretion of water and electrolytes 1. Electrolyte imbalances can occur (mainly hypokalemia) 2. Depends on type of diuretic

11. Diuretics Most efficient: Loop or High-ceiling Reduce edema associated with CHF Increase Urine output even if blood flow to kidney is diminished Hypokalemia KCL supplement given Lasix, Demadex, Bumex

12. Diuretics Most widely prescribed: Thiazides Mild to moderate HTN-primarily Hydrodiuril – hydrochlorothiazide (HCTZ) Hypokalemia Potassium supplement- KCL

13. Diuretics Potassium-sparing:prevent hypokalemia Mild HTN Used in combination with other diuretics No supplement taken Watch for hyperkalemia

14. Side effects Orthostatic hypotension Dry mouth,irritation Report: Electrolyte imbalance- hypokalemia (potasium<3.5) Disorientation dehydration

15. Implications for use Optimal time to admin.= AM Accurate intake and output Daily weights Monitor electrolyte imbalances

16. 2-Calcium Channel Blockers Emerged as major drug to treats HTN Used for arrythmias also Alternative to B-blocker ( esp.in Asthma patients)

17. Calcium Channel Blockers Action: blocks ca+ access to muscle cells contractility + conductivity of the ______________________ demand for oxygen PVR (relaxing arterioles)[peripheral vascular resistance]

18. Calcium Channel Blockers Examples Verapamil Very Procardia (nifedipine)-HTN Nice Cardizem (diltiazem)-arrythmias Drugs

19. Calcium Channel Blockers SIDE EFFECTS BP Bradycardia May precipitate A-V block Headache Abdominal discomfort Peripheral edema

20. 3-Angiotensin-Converting Enzyme Inhibitors “ACE” inhibitors Mainstay of oral vasodilator therapy Major breakthrough in treatment of HTN More effective when used with diuretics

21. ACE INHIBITORS Angiotensin Converting Enzyme (ends in PRIL) captopril enalapril benzapril (Capoten) (Vasotec) (Lotensin)

22. RENIN-ANGIOTENSIN- ALDOSTERONE AXN. BP excrete renin formation of angiotensin I angiotensin II = potent vasodilator Aldosterone release Na and H2O

23. ACE INHIBITORS ACTION peripheral vascular resistanse without Ø cardiac output Ø cardiac rate Ø cardiac contractility

24. Advantages Infrequent orthostatic hypotension Lack of aggravation of pulmonary disease. Lack of aggravation with Diabetes Mellitus Increase renal blood flow

25. Side effects Headache Orthostatic hypotension-infrequent Cough GI distress

26. Drug interactions Diuretics Alcohol Beta-blockers All the above enhance the effects

27. 4-Adrenergic Receptors Review of ANS Sympathetic Nervous System Alpha 1 = vasoconstriction Alpha 2 = feedback/vasodilation Beta 1 = increases heart rate Beta 2 = bronchodilation

28. A-Beta Adrenergic Blocking Agents Known as Beta-blockers Anti-adrenergic: Inhibit cardiac response to sympathetic nerve stimulation by blocking Beta receptors Decreases heart rate and Cardiac output Decreases blood pressure

29. Beta Adrenergic Blocking Agents Examples – “olol” names Beta 1: Atenolol Beta 1 and 2: Propranolol

30. Implications Can not be abruptly discontinued Check baseline b.p. Check patients of resp. condition- aggravates broncho-constriction

31. Side effects Bradycardia Bronchospasm, wheezing Diabetic: hypoglycemia Heart failure: edema,dyspnea,rhales

32. Interactions Antihypertensives- additive effect Anti-adrenergic effects. Enzyme inducing agents-enhance metabolism Indomethacin and salicylates:< controll

33. B-Alpha-1 adrenergic blockers Alternative if B-blockers and diuretics do not work Also used to treat mild to mod. urinary obstructive disease. (BPH)

34. Alpha-1 Adrenergic Blocking Agents Action: Block postsynaptic alpha-1 adrenergic receptors to produce arteriolar and venous vasodilation Reduces peripheral-vascular resistance

35. Side effects Drowsiness Headache Dizziness,tachycardia,fainting Weakness,lethargy Interactions: other antihypertensives (enhance effects)

36. Clinical Implications Side effects most prevalent with first dose Warn patient that this is normal Instruct pt. to lie down if dizzy,weak ….,etc.

37. Examples of Apha-1 blockers Cardura (doxazosin) Minipress (prazosin)

38. C-Centrally Acting Alpha-2 Agonists Stimulate Alpha-2 receptors in brainstem Decreases HR, SBP and DBP More frequent side effects – drowsiness, dry mouth, dizziness Never suddenly Discontinued = rebound HTN Clonidine [ Catapress] Methyldopa [Aldomet]

39. 5-Direct Acting Vasodilators Action: direct arteriolar smooth muscle relaxation, decreasing PVR Uses: HTN, renal disease, toxemia of pregnancy Ex: Apresoline, Minoxedil SE: tachycardia, orthostatic hypotension, dizziness, palpitations, nausea, nasal congestion

40. Patient Teaching for Antihypertensive drugs Take medication as prescribed Never discontinue without approval of healthcare provider Incorporate lifestyle changes, even if medication brings BP within normal Limits Check BP on regular basis and report significant variations (and pulse) Get out of bed slowly

41. Patient Teaching for Antihypertensive drugs Increase intake of potassium-rich foods, unless taking potassium sparing diuretics Weigh regularly and report abnormal weight gains or losses Do not take OTC drugs without checking with healthcare provider

42. Special notes on Treatment of Hypertension. Never combine: 1-Alpha or beta blocker and clonidine - antagonism 2-Nifedepine and diuretic synergism 3-Hydralazine with DHP or prazosin – same type of action 4-Diltiazem and verapamil with beta blocker – bradycardia 5-Methyldopa and clonidine Hypertension and pregnancy: No drug is safe in pregnancy Avoid diuretics, propranolol, ACE inhibitors, Sodium nitroprusside..etc Safer drugs: Hydralazine, Methyldopa, cardioselective beta blockers and prazosin

43. Hypertensive Crisis Hypertensive Urgencies: No progressive target-organ dysfunction. (Accelerated Hypertension) Hypertensive Emergencies: Progressive end-organ dysfunction. (Malignant Hypertension)

44. Hypertensive Urgencies Severe elevated BP in the upper range of stage II hypertension. Without progressive end-organ dysfunction. Examples: Highly elevated BP without severe headache, shortness of breath or chest pain. Usually due to under-controlled HTN.

45. Hypertensive Emergencies Severely elevated BP (>180/120mmHg). With progressive target organ dysfunction. Require emergent lowering of BP. Examples: Severely elevated BP with: - Hypertensive encephalopathy -Acute left ventricular failure with pulmonary edema -Acute MI or unstable angina pectoris -Dissecting aortic aneurysm

46. Hypertensive Emergencies 1-Cerebrovascular accident or head injury with high BP 2-Hypertensive encephalopathy 3-Angina or MI with raised BP 4-Acute renal failure with high BP 5-Eclampsia[ pregnancy hypertension ] Drugs: Sodium Nitroprusside (20-300 mcg/min) – dose titration and monitoring GTN (5-20 mcg/min) – cardiac surgery, LVF, MI and angina Esmolol (0.5 mg/kg bolus) and 50-200mcg/kg/min - useful in reducing cardiac work

47. The End