1. Topic Presentation Hypertension Monica Nicola 4 th Year PharmD candidate 1

2. Objectives Overview of hypertension Prevalence Epidemiology/Risk factors Pathophysiology Signs and Symptoms Diagnosis Treatment (Non-pharmacological and Pharmacological) Special Populations Clinical Pearls Role of Pharmacist 2

3. Overview of Hypertension Blood pressure is a measurement of the force against the walls of your arteries as your heart pumps through your body This requires the heart to work harder than normal to circulate blood through the blood vessels. Blood pressure is summarized by two measurements, systolic and diastolic, which depend on whether the heart muscle is contacting (systole) or relaxed between beats (diastole) and equate to a maximum and minimum, respectively. Function of cardiac output multiplied by peripheral resistance 3

4. JNC-7 Guidelines ClassificationSystolic BPDiastolic BP Normal<120 mmHg<80 mmHg Pre-Hypertension120-139 mmHg80-89 mmHg Stage 1140-159 mmHg90-99 mmHg Stage 2>160 mmHg>100 mmHg Hypertensive Urgency>180 mmHg >110 mmHg with no organ damage Hypertensive Emergency >180 mmHg >120 mmHg with end organ damage Resistant Hypertension Failure to reach goal BP while adhering to full doses of an appropriate three drug regimen that includes a diuretic 4

5. Prevalence At the age of 55 a person with normal blood pressure has a 90% lifetime risk of developing hypertension Hypertension control can greatly decrease morbidity and mortality 30% of those with hypertension are unaware that they have it Usually asymptomatic Or known as “the silent killer” About 50% being treated for hypertension are controlled 5

6. Epidemiology Nearly one billion people worldwide are affected 7.5 million deaths in 2004 (12.8% of world population) 51% and 45% of deaths from stroke and cardiovascular disease, respectively 50 million Americans have hypertension 6

7. Risk Factors Age Race African American Native American Hispanic Physical Inactivity Obesity High Sodium Family History Stress Chronic Conditions Diabetes Kidney Disease Sleep Apnea Cholesterol Smoking Alcohol Intake Just 2 drinks per day can increase blood pressure 7

8. Pathophysiology Arterial blood pressure: Cardiac Output and Peripheral Vascular Resistance Overall BP= HR x SV x PVR All three factors= Treatment 8

9. RAAS Pathway 9

10. 10

11. Signs and Symptoms Altered vision Fatigue Excruciating headaches Chest pain Shortness of breath Heartbeat Irregularity Bloody urine Confusion Fainting episodes 11

12. Diagnosis Two reading should be taken two minutes apart If in two different readings it is >5 mmHg, repeat No caffeine or alcohol for 3o minutes prior to a reading Patient should be relaxed for 5 minutes before reading Both feet should be on the floor and arm should be supported at heart level for most accurate reading 12

13. Treatment of Hypertension Non-Pharmacological Approaches Pharmacological Approaches 13

14. Non-Pharmacological Treatment 14

15. DASH Diet 15

16. Pharmacological Treatment Medication Diuretics ACEIs ARBs CCB B-Blockers A-1-Blockers Direct Renin Inhibitor Centrally-Acting A-2-Agonists Direct Arterial Vasodilators 16

17. Thiazide and Thiazide-Like Diuretics MOA: Blocks sodium reabsorption in distal renal tubules resulting in an increased secretion of sodium and chloride Monitoring Parameters Electrolytes Renal and Hepatic Function Uric Acid and Blood Glucose Drugs Hydrochlorothiazide (Microzide®) Chlorthalidone (Thalitone®, Hygroton®) Indapamide (Lozol®) Metolazone (Zaroxolyn®) 17

18. Loop Diuretics MOA: Blocks reabsorption of sodium and chloride in the ascending loop of Henle and distal renal tubule; increases electrolyte excretion Monitoring Parameters Creatinine and BUN Blood Pressure Serum Electrolytes Liver and Kidney Damage Drugs Furosemide (Lasix®)* Bumetanide (Bumex®)* Torsemide (Demadex®) Ethacrynic Acid (Edecrin®) 18

19. Potassium-Sparing Diuretics and Aldosterone Antagonists MOA: Blocks reabsorption of sodium in the distal tubules; aldosterone antagonism at Sodium/Potassium exchange site Monitoring Parameters Blood Pressure Serum Electrolytes Serum Creatinine Levels ECG if hyperkalemia occurs Drugs Amiloride (Midamore®)* Triamterene (Dyrenium®)* Spironolactone (Aldactone®)* Eplerenone (Inspra®) 19

20. Angiotensin-Converting Enzyme Inhibitors (ACEIs) MOA: Blocks the conversion of Angiotensin I to Angiotensin II, which is a potent vasoconstrictor Monitoring Parameters Heart Failure Hypertension Liver, Renal Function Drugs Lisinopril (Prinivil®) Benazepril (Lotensin®) Ramipril (Altace®) Enalapril (Vasotec®) Moexipril (Univasc®) Quinapril (Accupril®) 20

21. Angiotensin Receptor Blockers (ARBs) MOA: Blocks the binding of Angiotensin II to receptors thereby blocking vasoconstriction and aldosterone-secreting effects of Angiotensin II Monitoring Parameters Blood Pressure Renal Function Electrolytes Drugs Candesartan (Atacand®) Eprosartan (Teveten®) Irbesartan (Avapro®) Losartan (Cozaar®) Olmesartan (Benicar®) Telmisartan (Micardis®) Valsartan (Diovan®) 21

22. Calcium Channel Blockers Monitoring Parameters Arrythmia Blood Pressure Liver Function ECG Classes Dihydropyridines MOA: Directly blocks calcium influx into vascular smooth muscle Non-Dihydropyridines MOA: Inhibits calcium influx into arterial smooth muscle and causes vasodilation; slows heart rate 22

23. Calcium Channel Blockers Drugs Non-Dihydropyridines Verapamil (Calan®, Covera®,Verelan ® ) Diltiazem (Cardizem® ) Drugs Dihydropyridines Amlodipine (Norvasc®) Felodipine (Plendil®) Isradipine (DynaCirc®) Nicardipine SR (Cardene SR®) Nifedipine (Adalat CC, Procardia XL®) Nisoldipine (Sular®) 23

24. Beta Blockers: Nonselective MOA: Reduces chronotropic, inotropic and vasodilator responses by competing for binding sites that stimulate beta receptors 1 and 2 Monitoring Parameters Angina Blood Pressure Heart Rate Drugs Nadolol (Corgard®) Propranolol (Inderal®) Timolol (Blocadren®) 24

25. Beta Blockers: Selective MOA: Selectively blocks the Beta-1 adrenoreceptor Monitoring Parameters Angina Blood Pressure ECG Blood Glucose for Diabetics Liver Function Drugs Atenolol (Tenormin®)* Betaxolol (Kerlone®) Bisoprolol (Zebeta®) Metoprolol tartrate (Lopressor®)* Metoprolol succinate (Toprol XL®)* 25

26. Beta Blockers Intrinsic Sympathomimetic Activity Stimulates beta- adrenergic receptors Antagonizes stimulation of catecholamines Drugs Acebutolol (Sectral®) Carteolol (Cartrol®) Penbutolol (Levatol®) Pindolol (Visken®) Alpha and Beta-Blockers Beta-blocking activity decreases cardiac output Alpha-Blocking activity causes vasodilation and reduces vascular resistance Drugs Carvedilol (Coreg®) Labetolol (Trandate®) 26

27. Alpha-1 Blockers MOA: Block catecholamine uptake in smooth muscle cells by blocking alpha receptors, and resulting in vasodilation Monitoring Parameters Blood Pressure Heart Rate Drugs Doxazosin (Cardura®) Prazosin (Minipress®) Terazosin (Hytrin®) 27

28. Direct Renin Inhibitor MOA: Blocks the conversion of Angiotensinogen to Angiotensin I causing a decrease in Angiotensin II by blocking the effect of renin directly Monitoring Parameters Blood Pressure Renal Function Serum Potassium Drug in Class Aliskiren (Tekturna®) 28

29. Centrally-Acting Alpha-2 Agonists MOA: Stimulation of the alpha-2 receptor results in reduced sympathetic outflow and decreased heart rate and blood pressure Monitoring Parameters Blood Pressure Heart Rate Respiratory Rate Signs of Depression Drugs Clonidine (Catapres®) Methyldopa (Aldomet®) Guanfacine (Tenex®) Guanabenz (Wytensin®) Reserpine (Serpaline®) 29

30. Direct Arterial Vasodilators MOA: Direct relaxation of vascular smooth muscle causing a peripheral vasodilating effect Monitoring Parameters Blood Pressure Body Weight Fluid, Electrolyte Balance Pericardial Effusion Drugs Minoxidil (Loniten®) Hydralazine (Apresoline®) 30

31. Cardiac Output To lower preload: Diuretics Nitrates Morphine Sulfate Fluid restriction To lower contractility and HR: Beta Blockers Calcium Channel Blockers Antiarrhythmics To lower afterload: ACEIs ARBs Alpha and Beta Blockers Vasodilators CCBs 31

32. Hypertensive Urgency and Emergency Hypertensive urgency is a situation where the blood pressure is severely elevated [180 or higher for your systolic pressure (top number) or 110 or higher for your diastolic pressure (bottom number)], but there is no associated organ damage. Those experiencing hypertensive urgency may or may not experience one or more of these symptoms: Severe headache Shortness of breath Nosebleeds Severe anxiety A hypertensive emergency exists when blood pressure reaches levels that are damaging organs. Hypertensive emergencies generally occur at blood pressure levels exceeding 180 systolic OR 120 diastolic, but can occur at even lower levels in patients whose blood pressure had not been previously high. The consequences of uncontrolled blood pressure in this range can be severe and include Stroke Damage to the eyes and kidneys Loss of kidney function Angina (unstable chest pain) Pulmonary edema Heart Attack 32

33. Hypertensive Urgency and Emergency Urgency Treatment Clonidine: 0.1-0.2 mg PO x 1, then 0.05-0.1 every 1-2 hours (Max 0.7 mg) Captopril: 12.5-25 mg PO or SL; repeat as needed Labetalol: 200-400 mg PO, repeat every 2-3 hours Emergency Treatment Hydralazine: 20-40 mg/dose IM/IV bolus as needed Esmolol: 0.5-1 mg/kg IV bolus, then 50-300 mcg/kg/min continuous infusion Nicardipine: 5 mg/hr IV, increase by 2.5 mg/hr every 5 min until BP is under control 33

34. Special Populations 34

35. Hypertension in the Elderly Uncontrolled HTN JNC-7 Sometimes there is a titration schedule or decrease initial dosage to lower the risk for hypotension and adverse effects 35

36. Hypertension in Children and Adolescents BP greater than or equal to the 95 th percentile for age, sex and height on 3 different occasions Secondary hypertension Treatment: ACE Inhibitors, ARBs, Beta Blockers, CCBs and Thiazide Diuretics 36

37. Hypertension in Pregnancy 37

38. Clinical Pearls Be sure to have a at home monitoring kit Compliance is key to controlling HTN ACEs may cause a cough ACE, ARBs, and renin inhibitors can cause fetal abnormalities and should be avoided in childbearing age. African Americans do not respond well to beta blockers as a single agent Decrease alcohol intake Decrease sodium intake 38

39. Role of the Pharmacist Counsel patients on their medications Address side effects Enforce patient compliance Lifestyle modifications Let them know what other treatment options are available Assist or recommend to other providers on different treatment plans 39

40. References ”Hypertension." Cleveland Clinic. N.p.. Web. 1 Aug 2013.. "Group Health." Medicines for Congestive Heart Failure. N.p.. Web. 1 Aug 2013... Medscape. N.p.. Web. 1 Aug 2013... Medicine Net. N.p.. Web. 1 Aug 2013.. 40

41. Questions? 41