Hypertension

1. Hypertension

3. A CASE • Mr. Ahmed is a 42 years old male referred from local health center as he was noted to have BP of 180/110 for the last two months. Apart of occasional headache there was no other complains. He is a non-smoker and never consumed alcohol, his past medical history is only significant for allergic rhinitis. His father died years ago but he is not sure what was the cause of his death; his mother still alive and well, apart of mild DM on diet control. He has 3 brothers 44,45,46 years respectively, the eldest brother is hypertensive

4. Definition Hypertension is chronically elevated systolic and/or diastolic BP 140 systolic /90 diastolic mm Hg under satisfactory conditions of measurements. And confirmed by repeated accurate measurements over a period of time.

5. Our Patient Mr. Ahmed is a 42 years old male referred from local health center as he was noted to have BP of 180/110 for the last two months. Apart of occasional headache there was no other complains. He is a non-smoker and never consumed alcohol, his past medical history is only significant for allergic rhinitis. His father died years ago but he is not sure what was the cause of his death; his mother still alive and well, apart of mild DM on diet control. He has 3 brothers 44,45,46 years respectively, the eldest brother is hypertensive

6. Why is it important? 1-Silent killer and long life disease - IN OMAN In 1994 national survey Screened 4239 persons >20 23.7%--- 25.4% male & 22.2% female - In UK rule of halves!!

7. 2- Complication of hypertension -Sustained hypertension is associated with accelerated atheromatous disease of the blood vessels -Cerebrovascular disease Thromboembolic Intra cranial bleed TIA -Cardiovascular disease Myocardial infarction Heart failure Coronary artery disease

8. Renal failure Vascular disease… Aortic dissection. Accelerated / malignant hypertension. 3-Concomitant disease

9. Our Patient Mr. Ahmed is a 42 years old male referred from local health center as he was noted to have BP of 180/110 for the last two months. Apart of occasional headache there was no other complains. He is a non-smoker and never consumed alcohol, his past medical history is only significant for allergic rhinitis. His father died years ago but he is not sure what was the cause of his death; his mother still alive and well, apart of mild DM on diet control. He has 3 brothers 44,45,46 years respectively, the eldest brother is hypertensive

10. Classification

11. Our Patient Mr. Ahmed is a 42 years old male referred from local health center as he was noted to have BP of 180/110 for the last two months. Apart of occasional headache there was no other complains. He is a non-smoker and never consumed alcohol, his past medical history is only significant for allergic rhinitis. His father died years ago but he is not sure what was the cause of his death; his mother still alive and well, apart of mild DM on diet control. He has 3 brothers 44,45,46 years respectively, the eldest brother is hypertensive

12. Classification 1-HTN with no CVS risks / target organ damage 2-HTN with CVS risks 3-HTN with target organ damage 4-HTN with CVS risks & target organ damage

13. Aetiology of Hypertension Primary – 90-95% of cases – also termed “essential” or “idiopathic” Specific underlying?? environmental and genetic factors contribute.

14. Modifiable and non-modifiable risk factors • Age & gender • Genetic factors • Obesity • Sedentary life style • Salt intake • Alcohol • Stress • Smoking

15. Our Patient Mr. Ahmed is a 42 years old male referred from local health center as he was noted to have BP of 180/110 for the last two months. Apart of occasional headache there was no other complains. He is a non-smoker and never consumed alcohol, his past medical history is only significant for allergic rhinitis. His father died years ago but he is not sure what was the cause of his death; his mother still alive and well, apart of mild DM on diet control. He has 3 brothers 44,45,46 years respectively, the eldest brother is hypertensive

16. Secondary – about 5% of cases (specific disease or abnormality leading to sodium retention or peripheral vasoconstriction) -Renal or renovascular disease -Endocrine disease -Coarctation of the aorta -Iatrogenic (Drugs)

17. Making the diagnosis -HTN occasionally causes headache but other wise is symptomless. -Diagnosis made at routine examination (accident) or when complication arise. -Importance of EDUCATION and REGULAR CHECK UP especially for elderly individuals. -Objectives of assessing individual with high blood pressure -To confirm a persistent elevation of blood pressure. -To asses the overall cardiovascular risk. -To evaluate existing organ damage or concomitant disease -To search for possible causes of the hypertension

18. Crucial point when taking BP -Patient seated for 5 minutes (relaxed) -Patient seated, arm at heart level -Full bladder or recent use of tobaccos or caffeine (coffee) or tea. -Remove tight clothing. -Cuff should encircle 2/3 of arm > obese!! -Lower mercury slowly

19. -BP high…. What should I do?? Give the patient 5-10 minutes to relax and re-measure again. The diagnosis should be made after three measurements on at least two separate occasions Still HIGH Take a comprehensive history, including risk factors and ruling out a secondary cause of HPT. “White Coat” hypertension.

20. History Risk factors Features suggesting secondary causes Age<25 Renal disease Drugs Sweating, headache, anxiety (pheochromocytoma) End-organ CVS: Orthpnea, chest pain, palpation, ankle swelling. Brain: TIA, Vertigo, impared vision

21. Physical examination Full examination but focus in signs of Secondary hypertension. Features of Cushing’s syndrome Abdominal bruits (RAS) Femoral delay (Corc. Aorta) Palpable kidneys (PS) Organ damage CVS:Apex (heave), S4, dependent odema, rales. Eye: retinal changes Neurological defects.

22. Lab test The minimum Urinalysis Blood glucose Serum urea, creatinine, Na and K. ECG Fasting serum cholesterol Selected patients Chest CXR Echo Renal ultrasound/angiography Urinary catecholamine

23. In diabetes mellitus, aim for > 130/80 mmHg • In non-diabetic, the treatment goal is 140/85 mmHg • In proteinuria, aim for >125/75 mmHg British Hypertension Society 2004 guidelines The Therapeutic goals www.hyp.ac.uk/bhs/resources/guidelines.htm

24. Modifications • Weight reduction • Diet • Dietary sodium reduction • Physical activity • Cessation of Alcohol consumption

26. Major Anti-Hypertensive Drugs • Diuretics • β-blockers • Calcium channel blockers • ACE inhibitors & ARB • α1-adrenoceptor blockers • Centrally-acting adrenergic drugs • vasodilators

27. Diuretics LOOPdiuretics Thiazides K-retainingdiuretics

28. Thiazides Action: • inhibit reabsorption of Na & Cl in distal convolutedtubules, resulting in retention of water. • Prototype: HYDROCHLOROTHIAZIDE • (dose: 6.25-25 mg PO once daily) Therapeutic indications: • effective as ACE inhibitors & CCB in prevention of CHD & non-fatal MI in HTN. • useful in combination therapy with ACEI & β-Blockers. • Useful in the treatment of black or elderly patients & those with CRF.

29. Side-effects: • hypokalemia (in 70%) → cardiac arrhythmia • hyperglycaemia (in 10%) • hyperuricaemia (in 70%) • increase. LDL … high doses only. Contraindication: • gout • patients receiving lithium • Should be avoided in hypertensive diabetics or patients with hyperlipidemia NB. Thiazides are ineffective if GFR<30ml/min

30. K-retaining diuretics(spironolactone, amiloride) Action: • spironolactone inhibits the aldosterone-mediated reabsorption of Na & secreation of k. • amiloride blocks Na cannels in distal tubules • Dose: spironolactone → 12.5-200 mg/d PO amiloride → 5-20 mg/d PO Therapuetic indication: • drug of choice in HTN due to primary aldosteronism • limit K loss in patient treated with thiazides Side-effects: • sexual dysfunction • painful gynecomastia

31. LOOP diuretics Action: • block Na/K/Cl co-transport in thick ascending loop of Henle, resulting in retention of Na, Cl & water. • Prototype: frusemide • (dose : 20-160 mg/d PO/IV/ IM) Therapuetic indication: • no role in routine management of HTN except in patients with impaired renal function or heart failure. Side-effect: (rare) • interstitial nephritis of kidney • ototoxicity • acute hypovolemia

32. β-blockers Classes: • non-selective agents act on β1/ β2 (propranolol). • cardio-selective act on β1 (metoprolol,atenolol,acebutolol,bisprolol). selectivity lost at high doses • drugs act on β/α1blockers (labetalol,carvidilol). Mechanism of action

33. Therapuetic indications: • cardioselective (atenolol) in hyertensive patient with CHD. • (labetolol) used in treatment of malignant HTN. • useful in treatment of: atrial tachyarrythmia/fibrillation.

34. Dose: • Atenolol: 25-100 mg PO once daily • Metoprolol: 50-200 mg PO once daily • Propranolol: 40-160 mg PO twice daily • Labetalol: 20-30 mg IV over 2 min followed by 40-80mg at 10-min intervals

35. Side-effects: • contraction of smooth muscles (bronchospasm, Raynaud’s phenomenon). • 2nd & 3rd degree heart block. • penetration of CNS ( depression & nightmares ). • tiredness & fatigue. • inc. in triglycerides & dec. HDL cholesterols. • type II DM… 15%

36. Contraindication: • asthma & other forms of reactive airway disease. • heart block. • Depression.

37. Calcium channel blockers Action: • Block openings of voltage-gated (L-type) Ca channels thereby prevent Ca entry into:  cardiac muscles →dec cardiac contractility  vascular smooth muscles →vasodilatation Classes: dihydropyridine (nifidipine,felodipine, amlodipine) act on vascular smooth muscles.  non- dihydropyridine (verapamil,diltiazem) act on cardiac muscle cells.

38. Therapeutic indication: • dihydropyridine CCB are as effective as ACEI & diuretics in dec. overall cardiovascular & cerebrovascular accidents. • excellent outcomes in elderly diabetic patients & isolated systolic HTN. • diltiazem & verpamil (without β-blockers) in treatment of angina.

39. Dose: • Diltiazem: 120-540 mg PO once daily • Verapamil: 120-480 mg PO once daily • Nifedipine: 30-120mg PO once daily • Amlodipine: 2.5-10 mg PO once daily Side-effects: • Headache • Flushing • Ankle oedema • Constipation contraindication: • verapamil in LVD & heart block

40. ACEI • Mechanism of Action

41. Therapeutic indication: • hypertensive patients with diabetes nephropathy. • left venticular dysfunction • after MI Dosage: • captopril …25-150 mg/day • lisinopril … 5-80 mg/day • ramipril … 2.5-20mg/daily

42. Side-effects: • dry cough …(10-20)% • hyperkalemia (<2%) Contraindication: • bilateral renl artery stenosis • hyperkalemia (if K>5.6mmol/l) • pregnancy

43. ARB (Angiotensin II Antagonists) • Drug name: Losartan ,Valsartan • Mechanism of action: vasodilation & block aldosterone secretion (similar to ACEI) Therapeutic indication: • indicated in patients intolerant to ACEI Dose: • losartan … 25-100 mg PO once or twice daily • valsartan … 80 mg/d PO; may increase to 160 mg/d if needed Side effects: • hyperkalaemia Contraindication: • same as ACEI

44. Alpha1-adrenergic blockers (Prazosin & Terazosin) Action: • Selectively block postsynaptic alpha1-adrenergic receptors. Dilate arterioles and veins, thus lowering blood pressure. Therapeutic indication: • Prazosin treats HTN with prostatic hypertrophy Dose: • Prazosin 1-40 mg PO twice daily • Terazosin: 1-20 mg PO once daily Side–effects: • reflex tachycardia & 1st dose syncope Contraindicated in renal incontinence.

45. Centrally acting agents mechanism of action: A- stimulation of α-adrenergic receptor in CNS lowers central sympethatic outflow. B- stimulation of pre-synaptic α-receptor causes feedback inhibition of norepinephrine release from peripheral sympethatic nerve terminal. 1- ↓ HR 2- ↓ CO 3- ↓ PR

46. Drugs: • Methyldopa .. 250 mg PO once/twice daily • Clonidine .. 0.2-1.2 mg PO twice daily Therapuetic indication: • rarely indicated in routine of HTN management • α-methyldopa is drug of choice for chronic HTN in pregnancy.

47. Side effects: • 1- sedation • 2- dry mouth • 3- depression • 4- excessive bradycardia (not used with beta blockers) • 5- orthostatic hypotension • 6- (α-methyldopa): autoimmune haemolytic anaemia, pyrexia, hepatitis • 7- rebound hypertension if clonidine discontinued abruptly

48. Direct vasodilators Mechanism of action: • Tow drugs: Minoxidil – hydralazine - open vascular ATP-sensitive potassium channels. Therapeutic indicates: • Hydralazine: drug of choice for pre-eclampsia (HTN in pregnancy). • minoxidil: main indication in HTN with chronic renal failure.

49. Dose: • Hydralazine: 10-20 mg/dose IV/IM q4-6h • Minoxidil: 5 mg PO once daily Side-efects: • hypotension & reflex tachycardia • peripheral oedema • minoxidil causes hirsuitism

50. Na, H2O retention PR Blood volume Cardiac output Thiazide Diuretics Decrease in BP