2. Hypertension Nouf Aloudah, M.S Clinical Pharmacy Lecturer King Saud University

3. Hypertension Why to treat hypertension … 150/95 mmHg ?!!! 150/95 mmHg ?!!! 200/100 mmHg ?!!! 200/100 mmHg ?!!! So what? So what?

4. Terri before and 15 years after stroke and now she is dead  And many other sad stories ….. And many other sad stories …..

5. Hypertension Hypertension means Hypertension means “ many organs in the body are under attack ”

6. Hypertension Diagnosis a late stage when target-organ damage has already started target-organ damage has already started + the optimum time to start treatment remains "under discussion."

7. Hypertension complications premature cardiovascular disease premature cardiovascular disease increases the risk of heart failure at all ages increases the risk of heart failure at all ages Left ventricular hypertrophy is a common problem in patients with hypertension Left ventricular hypertrophy is a common problem in patients with hypertension Hypertension is the most common and most important risk factor for stroke Hypertension is the most common and most important risk factor for stroke Hypertension is the most important risk factor for the development of intracerebral hemorrhage Hypertension is the most important risk factor for the development of intracerebral hemorrhage Hypertension is a risk factor for chronic renal insufficiency and end-stage renal disease Hypertension is a risk factor for chronic renal insufficiency and end-stage renal disease Marked elevations in blood pressure can cause an acute, life-threatening emergency Marked elevations in blood pressure can cause an acute, life-threatening emergency

8. Hypertension USA # 1.5 billion estimated to be hypertensive by 2025 1.5 billion estimated to be hypertensive by 2025 Risk is 90% for individuals in developing country Risk is 90% for individuals in developing country

9. Hypertension USA # NHANES 1999-2000 NHANES III 1991- 1994 NHANES III 1988- 1991 NHANES II 1976- 1980 7068.47351Awarenes s 5953.65531Treatment 3427.42910Control*

10. Hypertension Saudi # 9.1% and 8.7% ≥160/95 mmHg 9.1% and 8.7% ≥160/95 mmHg 20.4% 25.9% ≥ 140/90 mmHg 20.4% 25.9% ≥ 140/90 mmHg 13 700 13 700 Arterial hypertension in Saudi Arabia Arterial hypertension in Saudi Arabia Volume 4, Issue 2, 1998, Page 382 Volume 4, Issue 2, 1998, Page 382 M.M. Al-Nozha, M.S. Ali and A.K. Osman M.M. Al-Nozha, M.S. Ali and A.K. Osman one fourth of Riyadh city people are unaware of their high blood pressure, and also we can note that those with higher social class are prone to hypertension. one fourth of Riyadh city people are unaware of their high blood pressure, and also we can note that those with higher social class are prone to hypertension. Wahid Saeed AA, 1996 Wahid Saeed AA, 1996

11. Hypertension USA and Saudi # Lots of effective treatment Lots of effective treatment Overwhelming evidence Overwhelming evidence No control  ??? Compliance!!!! Compliance!!!! Pharmacist plays a big rule! Pharmacist plays a big rule! Lancet, augest 18. 2007 Lancet, augest 18. 2007

12. Hypertension The Role of Pharmacists The Role of Pharmacists in the Detection, Management, and Control of Hypertension: A National Call To Action The Role of Pharmacists in the Detection, Management, and Control of Hypertension: A National Call To Action Pharmacotherapy 20(2):119-122, 2000 Community Pharmacies most accessible once a month most accessible once a month Knows all the medications, cost of drugs important link between the physician and patient. work together to achieve goals developie optimal, cost-effective strategies that use the principles and guidelines from the JNC-VI. developie optimal, cost-effective strategies that use the principles and guidelines from the JNC-VI.

13. Hypertension The Role of Pharmacists The Role of Pharmacists in the Detection, Management, and Control of Hypertension: A National Call To Action The Role of Pharmacists in the Detection, Management, and Control of Hypertension: A National Call To Action Pharmacotherapy 20(2):119-122, 2000 Integrated Health Systems 1977 326 pt Blindly evaluate 2 clinical pharmacist and 3 physicians pharmacists significantly higher for the selection of the most appropriate drug therapy compared with physicians. the pharmacist-managed group (97%) had controlled blood pressure compared with the physician-managed group (78%)!

14. Hypertension Diuretics Mechanism of action Increase renal execration of sodium and water Increase renal execration of sodium and water Decrease fluid volume within the intravascular compartment Decrease fluid volume within the intravascular compartment

15. Hypertension Diuretics Potassium wasting Chlorthalidone (hygroton), Hydrochlorothiazide (hydrodiuril, esidrix), Indapamide (lozol), Metalazone (zaroxolyn) Chlorthalidone (hygroton), Hydrochlorothiazide (hydrodiuril, esidrix), Indapamide (lozol), Metalazone (zaroxolyn) ↑ cholesterol and TG ↑ glucose and uric acid Hypokalemia ↑ calcium conc ↑

16. Hypertension Diuretics Loops Frusamide (lasix), ethacrynic acid (edecrin), bumetanide (bumex), torsemide (demadex) Frusamide (lasix), ethacrynic acid (edecrin), bumetanide (bumex), torsemide (demadex) Short duration of action Short duration of action No hypercalcemia No hypercalcemia

17. Hypertension Diuretics Potassium sparing Potassium sparing Amiloride (midamor), spironolactone (aldactone), triameterene (dyrenium) Amiloride (midamor), spironolactone (aldactone), triameterene (dyrenium) Hyperkalemia, gynacomastia with spironolactone Hyperkalemia, gynacomastia with spironolactone

18. Hypertension sympatholytic drugs Beta adrenergic blockers Beta adrenergic blockers Alpha and beta blockers Alpha and beta blockersLabetalol Alpha blocker Alpha blocker Prazosin, doxazosin, terazosin Presynaptic adrenergic inhibitors Presynaptic adrenergic inhibitors Guandrel, guanethidin, reserpine Centrally acting agents Centrally acting agents Clonidine, guanabenz, guanfacine, and methyldopa Ganglionic blockers Ganglionic blockers

19. Hypertension Beta-Blockers Mechanism of action: ↓ heart rate and force of contraction ↓ heart rate and force of contraction ↓ cardiac output ↓ cardiac output Other mechanism postulated Other mechanism postulated

20. Hypertension Beta-Blockers Acebutolol (sectral) Acebutolol (sectral) Atenolol (tenormin) Atenolol (tenormin) Betaxolol (kerion) Betaxolol (kerion) Bisprolol (zebeta) Bisprolol (zebeta) Carteolol (cartrol) Carteolol (cartrol) Carvedilol (coreg) Carvedilol (coreg) Metoprolol (lopressor, toprol XL) Metoprolol (lopressor, toprol XL) Nadolol (corgard) Nadolol (corgard) Penbutolol (levatol) Penbutolol (levatol) Pindolol (visken) Pindolol (visken) Propranolol (inderal) Propranolol (inderal) Timolol (blocadren Timolol (blocadren Bronchospasm Bradycardia Heart failure Mask hypoglycemia and delay recovery Impaired peripheral circulation ↓Exercise tolerance

21. Hypertension vasodilators Hydralazine (apresoline) Hydralazine (apresoline) Injectable for emergency Onset of action: I.V.: 5-20 minutes Minoxidil (loniten) Minoxidil (loniten) For renal failure patient who are resistant to everything Hair growth, fluid accumulation

22. Hypertension calcium antagonists Mechanism of action Block calcium entry into vascular smooth muscle Block calcium entry into vascular smooth muscle vasodilatation vasodilatation ↓ peripheral resistance ↓ peripheral resistance ↓ heart rate ↓ heart rate ↓ Myocardial contractile force ↓ Myocardial contractile force

23. Hypertension calcium antagonists Nondihydropyridines Diltiazim (cardizem) Diltiazim (cardizem) Verapamil (isoptin) Verapamil (isoptin)Dihydropyridines Amlodipine (norvasc) Amlodipine (norvasc) Felodipine (plendil) Felodipine (plendil) Isradaoine (dynacirc) Isradaoine (dynacirc) Nifedipine (procardia, adalat) Nifedipine (procardia, adalat) Nisoldipne (sular) Nisoldipne (sular) Nondihydropyridines Conduction defects Worsening systolic dysfunction Gingival hyperplasia Constipation (verapamil) Dihydropyridines Ankle edema Flushing Headache Gingival hyperplasia

24. Hypertension Renin Angiotensin Aldosterone Inhibitors Angiotensin converting enzyme inhibitors (ACEI) Angiotensin converting enzyme inhibitors (ACEI) Block conversion of angiotensin I to angiotensin II Block conversion of angiotensin I to angiotensin II (angiotensin II cause vasoconstriction) (angiotensin II cause vasoconstriction) Angiotensin II receptor blockers (ARBs) Angiotensin II receptor blockers (ARBs) Block the angiotensin II receptor on the cells Block the angiotensin II receptor on the cells

25. Hypertension ACEI Benzopril (lotensin) Benzopril (lotensin) Captopril (capoten) Captopril (capoten) Enalapril (vasotec) Enalapril (vasotec) Fosinopril (monopril) Fosinopril (monopril) Lisinopril (zestril) Lisinopril (zestril) Moexipril (univasc) Moexipril (univasc) Perindopril (aceon) Perindopril (aceon) Quinapril (accupril) Quinapril (accupril) Ramipril (altace) Ramipril (altace) Trandolapril (mavik) Trandolapril (mavik) Cough Angioedema Hyperkalemia Rash Loss of taste Leukopenia Pregnancy category C and D

26. Hypertension ARBs Candesartan (atacand) Candesartan (atacand) Eprosartan (tevetan) Eprosartan (tevetan) Irbesartan (avapro) Irbesartan (avapro) Losartan (cozaar) Losartan (cozaar) Olmesartan (benicar) Olmesartan (benicar) Telmisartan (micardis) Telmisartan (micardis) Valsartan (diovan) Valsartan (diovan) Hyperkalemia Very rare angioedema Pregnancy category C and D

28. Monotherapy versus combination

29. Compelling indications for specific pharmacotherapy

30. Large outcome trials for HTN