Cpt htn march 2010


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Cpt htn march 2010

  2. 2. E. Brown-Myrie, Pharm. D. Introduction Definition An elevation of either the systolic blood pressure, the diastolic blood pressure or both. BP = CO x PVR              Hypertension is a sign of many underlying disease processes, the majority of which cause no symptoms.   It is a major risk factor for the development of stroke, renal failure, myocardial infarction and coronary artery disease. It affects 10 – 15% of the world’s population and often coexists with other disease conditions, diabetes being the most prevalent.  
  3. 3. E. Brown-Myrie, Pharm. D. Blood Pressure Measurement and Clinical Evaluation (JNC VII) Classification and Management of Blood Pressure for Adults BP Classification Systolic (mm Hg) Diastolic (mm Hg) Normal <120 and <80 Prehypertension 120-139 or 80-89 Hypertension ‡ Stage 1 140-159 or 90-99 Stage 2 > 160 or > 100 JNC7 = Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure Hypertension 2003;42:1206–1252
  4. 4. E. Brown-Myrie, Pharm. D. Recommendations for Follow-up Based on Initial Blood Pressure Measurements for Adults <ul><li>Initial Blood Pressure (mm Hg)* </li></ul><ul><li>Systolic Diasstolic Follow-up Recommended † </li></ul><ul><li><130 <85 Recheck in 2 years </li></ul><ul><li>130-139 85 – 89 Recheck in 1 year‡ </li></ul><ul><li>140-159 90-99 Confirm within 2 months ‡ </li></ul><ul><li>160-179 100-109 Evaluate or refer to source of care within 1 month </li></ul><ul><li>> 180 > 110 Evaluate or refer to source of care immediately or within 1 week depending on clinical situation </li></ul><ul><li>If systolic and diastolic categories are different, follow recommendations for shorter time follow-up (e.g 160/86 mm Hg should be evaluated or referred to source of care within 1 month). </li></ul><ul><li>† Modify the scheduling of follow-up according to reliable information about past blood pressure measurements, other cardiovascular risk factors, or target organ disease. </li></ul><ul><li>‡ Provide advice about lifestyle modifications. </li></ul>
  5. 5. E. Brown-Myrie, Pharm. D. Components of Cardiovascular Risk Stratification in Patients with Hypertension <ul><li>Major Risk Factors </li></ul><ul><li>Smoking Cigarette Smoking </li></ul><ul><li>Dyslipidemia Obesity (BMI > 30 kg/m 2 </li></ul><ul><li>Diabetes Mellitus Microalbuminuria or GFR < 60 mL/min </li></ul><ul><li>Age older than 55 for men, 65 for women </li></ul><ul><li>Sex (men and postmenopausal women) </li></ul><ul><li>Family history of cardiovascular disease; women under age 65 or men under age 55 </li></ul><ul><li>Target Organ Damage/Clinical Cardiovascular Disease </li></ul><ul><li>Heart Disease </li></ul><ul><li>Left ventricular hypertrophy Nephropathy (CKD) </li></ul><ul><li>Angina/prior myocardial infarction Stroke or transient ischemic attack </li></ul><ul><li>Prior coronary revascularization Peripheral Arterial disease </li></ul><ul><li>Heart failure Retinopathy </li></ul><ul><li>Hypertension 2003;42:1206–1252 </li></ul>
  6. 6. E. Brown-Myrie, Pharm. D. Risk Stratification and Treatment Blood Pressure Lifestyle Modification Drug therapy Normal (<120/80) Encourage Without With compelling Compelling Indications Indications Pre-hypertension Yes No drug therapy Drugs to treat com- 120-139/80-89) pelling indications Stage 1 Yes Thiazide-type Drugs for the com- (140-159/90-99) diuretics for most. pelling indications ‡ May use ACEI, Other agents (diuretics. ARB, BB, CCB ACE, ARB, BB, CCB or combination as needed Stage 2 Yes Two drug As Above ( > 160/ > 100) combination for most † † Initial combined therapy should be used cautiously in those at risk for orthostatic hypotension. ‡ Treat patients with chronic renal disease or diabetes to BP goal of <130/80. Hypertension 2003;42:1206–1252
  7. 7. E. Brown-Myrie, Pharm. D. EVALUATION & DIAGNOSIS <ul><li>Blood Pressure Measurement </li></ul><ul><li>Complete Medical History </li></ul><ul><li>Physical Examination </li></ul><ul><li>Laboratory Measurements </li></ul>
  8. 8. E. Brown-Myrie, Pharm. D. BLOOD PRESSURE MEASUREMENTS <ul><li>Use properly calibrated and validated instrument </li></ul><ul><li>Patient should be seated quietly for at least 5 minutes </li></ul><ul><li>Use appropriate size cuff (cuff bladder encircles at least 80% of arm) </li></ul><ul><li>At least two measurements should be made </li></ul><ul><li>SBP is the first sound heard; DBP is the point before disappearance of sounds </li></ul><ul><li>Hypertension 2003;42:1206–1252 </li></ul>
  9. 9. E. Brown-Myrie, Pharm. D. COMPLETE MEDICAL HISTORY <ul><li>Known duration and level of elevated BP </li></ul><ul><li>History or symptoms of CHD, HF, CVA, peripheral vascular disease, DM, dyslipidemia, renal disease </li></ul><ul><li>Family history of CV disease, DM, etc. </li></ul><ul><li>History of recent changes in weight </li></ul><ul><li>Dietary assessment- Na, alcohol intake </li></ul><ul><li>History of prescribed and over-the-counter drugs </li></ul><ul><li>Hypertension 2003;42:1206–1252 </li></ul>
  10. 10. E. Brown-Myrie, Pharm. D. PHYSICAL EXAMINATION Fundoscopic examination (arteriolar narrowing, focal arteriolar constrictions, AV nicking, hemorrhages, exudates and disc edema) Neck examination (carotid bruits, distended veins, enlarged thyroid) Heart (abnormal rates & rhythms, increased size, murmurs, third and fourth sounds) Lung (rales, evidence of bronchospasm) Abdomen (bruits, enlarged kidneys, masses, abnormal aortic pulses) Extremities (diminished or absent peripheral pulses,bruits and edema)
  11. 11. E. Brown-Myrie, Pharm. D. LABORATORY MEASUREMENTS <ul><li>Urinalysis </li></ul><ul><li>Complete Blood Count </li></ul><ul><li>Blood chemistry </li></ul><ul><li>Electrocardiogram </li></ul>
  12. 12. E. Brown-Myrie, Pharm. D. MANAGEMENT OF HYPERTENSION <ul><li>Goals of Therapy </li></ul><ul><li>Lifestyle Modifications </li></ul><ul><li>Pharmacologic Treatment </li></ul>
  13. 13. E. Brown-Myrie, Pharm. D. Goals of Therapy <ul><li>Reduce cardiovascular and renal morbidity and mortality </li></ul><ul><li>Achieve and maintain SBP below 140 mm Hg and DBP below 90 mm Hg </li></ul><ul><ul><li>Diabetes: <130/80 </li></ul></ul><ul><ul><li>RF/HF: <130/80 </li></ul></ul><ul><li>Control modifiable risk factors for CV disease </li></ul><ul><ul><ul><ul><ul><li>Hypertension. 2003;42:1206–1252 </li></ul></ul></ul></ul></ul>
  14. 14. 2007 – AHA Scientific Statement E. Brown-Myrie, Pharm. D. AREA BP Target (mm Hg) General CAD Prevention <140/90 High CAD risk <130/80 CAD LVD <130/80 <120/80 Circulation. 2007;115:2761-2788
  15. 15. 2007 – AHA Scientific Statement AREA BP Target (mm Hg) Specific Drug Indications General CAD Prevention <140/90 Monotherapy or combination therapy: • ACEI (or ARB), CCB, or thiazide diuretic first-line High CAD risk <130/80 Monotherapy or combination therapy: • ACEI (or ARB), CCB, or thiazide diuretic first-line CAD LVD <130/80 <120/80 β-blocker and ACEI or ARB ACEI or ARB and β-blocker and aldosterone antagonist and diuretic Circulation. 2007;115:2761-2788
  16. 16. E. Brown-Myrie, Pharm. D. Lifestyle Modifications to Manage Hypertension <ul><li>Weight Reduction (BMI 18.5 – 24.9 kg/m 2 ) </li></ul><ul><li>Adopt DASH (Dietary Approaches to Stop Hypertension) Eating Plan </li></ul><ul><li>Increase Aerobic Exercise </li></ul><ul><li>Reduce Sodium intake to no more than 100 mmol/day (2.4 g sodium or 6 grams NaCl) </li></ul><ul><li>Limit consumption of alcohol to 1 oz or 30 mL ethanol (24 oz beer,10 oz wine,etc.) </li></ul><ul><li>Stop smoking </li></ul>
  17. 17. E. Brown-Myrie, Pharm. D. PHARMACOLOGIC TREATMENT <ul><li>General Guidelines </li></ul><ul><li>Use low dose of antihypertensive and titrate up slowly </li></ul><ul><li>Optimal formulation should provide 24 hour efficacy with once daily dose </li></ul><ul><li>Long acting formulations are preferred </li></ul><ul><li>Low dose combinations provide additional antihypertensive efficacy </li></ul>
  18. 18. E. Brown-Myrie, Pharm. D. Treatment - Special Considerations <ul><li>Demographics – Blacks respond better to diuretics & CCBs </li></ul><ul><li>Concomitant Diseases and Therapies – antihypertensives may worsen or improve coexisting condition </li></ul><ul><li>Quality of Life – antihypertensives used should improve quality of life (watch adverse effects) </li></ul><ul><li>Cost – cost may be a barrier to BP control (consider generics) </li></ul>
  19. 19. E. Brown-Myrie, Pharm. D. Treatment Recommendations <ul><li>Several classes of drugs (ACEIs, ARBs, BBs, CCBs and thiazide-type diuretics will reduce complications of hypertension </li></ul><ul><li>Thiazide-type diuretics have been supported in many outcome trials as been unsurpassed in preventing cardiovascular complications of HTN </li></ul><ul><li>Thiazide-type diuretics should be used as initial therapy for most patients with hypertension (either alone or in combination) </li></ul>
  20. 20. E. Brown-Myrie, Pharm. D. Treatment Recommendations cont. <ul><li>Concomittant diseases (compelling indications) may require use of other antihypertensives as initial therapy </li></ul><ul><li>Where a drug is contraindicated or not tolerated, another class with proven efficacy should be used </li></ul>
  21. 21. E. Brown-Myrie, Pharm. D. Clinical Trial & Guideline Basis for compelling Indications for Drug Therapy Compelling Indication Diuretic BB ACEI ARB CCB Aldo ANT Clinical Trials Basis Heart Failure • • • • • ACC/AHA Heart Failure Guidelines, MERIT-HF, COPERNICUS,CIBIS, SOLVD,AIRE, TRACE, ValHEFT,RALES Post MI • • • ACC/AHA Heart Failure Guidelines, BHAT, SAVE, Capricorn, EPHESUS High Coronary disease risk • • • • ALLHAT, HOPE, ANBP2, LIFE,CONVINCE Diabetes • • • • • NKF-ADA Guideline, UKPDS, ALLHAT, Chronic Kidney disease • • NKF Guideline, Captopril Trial, RENAAL,IDNT,REIN, AASK Recurrent stroke prevention • • PROGRESS
  22. 22. Study Abbreviations <ul><li>AASK African American Study of Kidney Disease & Hypertension </li></ul><ul><li>ACC/AHA American College of Cardiology/American Heart Association </li></ul><ul><li>AIRE Acute Infarction Ramipril Efficacy </li></ul><ul><li>ALLHAT Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial </li></ul><ul><li>ANBP2 Second Australian National Blood Pressure Study </li></ul><ul><li>BHAT Beta Blocker Haert Attack Trial </li></ul><ul><li>CIBIS Cardiac Insufficiency Bisoprolol Study </li></ul><ul><li>CONVINCE Controlled Onset Verapamil Investigation of Cardiovascular Endpoints </li></ul>E. Brown-Myrie, Pharm. D.
  23. 23. Study Abbreviations <ul><li>COPERNICUS –Carvedilol Prospective Randomized Cumulative Survival Study </li></ul><ul><li>EPHESUS Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study </li></ul><ul><li>HOPE Heart Outcomes Prevention Evaluation Study </li></ul><ul><li>IDNT Irbesartan Diabetic Nephropathy Trial </li></ul><ul><li>LIFE Losartan Intervention for Endpoint Reduction in Hypertension Study </li></ul>E. Brown-Myrie, Pharm. D.
  24. 24. Study Abbreviations <ul><li>MERIT-HF Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure </li></ul><ul><li>NKF-ADA National Kidney Foundation- AmericReduction an Diabetes Association </li></ul><ul><li>PROGRESS Perindopril Protection Against Recurrent Stroke Study </li></ul><ul><li>RALES Randomized Aldactone Evaluation Study </li></ul><ul><li>REIN RamiprilEfficacy in Nephropathy Study </li></ul><ul><li>RENAAL of Endpoints in Non Insulin Dependent Diabetes Mellitus With the Angiotensin II Antagonist Losartan Study </li></ul>E. Brown-Myrie, Pharm. D.
  25. 25. Study Abbreviations <ul><li>SAVE Survival and Ventricular Enlargement Study </li></ul><ul><li>SOLVD Studies of Left Ventricular Dysfunction </li></ul><ul><li>TRACE Trandolapril Cardiac Evaluation Study </li></ul><ul><li>UKPDS United Kingdom Prospective Diabetes Study </li></ul><ul><li>ValHEFT Valsartan Heart Failure Trial </li></ul>E. Brown-Myrie, Pharm. D.
  26. 26. E. Brown-Myrie, Pharm. D. Special Considerations- Black Patients <ul><li>There is increased prevalence, severity and impact of HTN in black patients </li></ul><ul><li>Blacks show reduced responsiveness to ACEIs, BBs and ARBs compared to diuretics and CCBs </li></ul><ul><li>Reduced responsiveness may be improved with drug combinations especially those including diuretics </li></ul><ul><li>ACEI – induced angio-edema may be more common in blacks than any other group </li></ul>
  27. 27. E. Brown-Myrie, Pharm. D. Special Considerations – Elderly Patients <ul><li>HTN is very common in elderly. SBP is better predictor of CV events and all cause mortality. </li></ul><ul><li>Some older patients exhibit pseudo-hypertension due to excessive vascular stiffness </li></ul><ul><li>HTN therapy should begin with lifestyle modifications </li></ul>
  28. 28. E. Brown-Myrie, Pharm. D. Special Considerations – Elderly Patients cont. <ul><li>When pharmacologic treatment is used the dose should be reduced by half. </li></ul><ul><li>Thiazide diuretics or BBs in combination with thiazides are recommended initial therapy. </li></ul><ul><li>Diuretics are preferred in isolated systolic hypertension. </li></ul>
  29. 29. E. Brown-Myrie, Pharm. D. Special Considerations- Young Patients <ul><li>Lifestyle modification should be first recommendation </li></ul><ul><li>Recommendations for choice of drugs are the same as for adults but dosages should be smaller and adjusted appropriately. </li></ul><ul><li>ACEIs and ARBs should not be used in pregnant or sexually active girls. </li></ul>
  30. 30. E. Brown-Myrie, Pharm. D. Special Considerations – Pregnant Patients <ul><li>Therapy should minimize risks to mother but should also not compromise well-being of fetus </li></ul><ul><li>Antihypertensives taken before pregnancy (except ACEIs and ARBs) may be continued. </li></ul><ul><li>Methyldopa and hydralazine are most extensively evaluated so should be the recommended when first diagnosed </li></ul><ul><li>BBs compare favourably with methyldopa but use in early pregnancy may be associated with growth retardation of fetus </li></ul><ul><li>ACEIs and ARBS cause serious neonatal problems </li></ul>
  31. 31. E. Brown-Myrie, Pharm. D. Special Considerations – Cerebrovascular Disease <ul><li>Antihypertensive medications are indicated in CVAs, however it is appropriate to withhold treatment immediately after an event, unless BP is very high </li></ul><ul><li>Control BP at 160/110 mm Hg until condition stabilizes </li></ul><ul><li>Recurrent stroke are lowered by combination of an ACEI and thiazide diuretic </li></ul>
  32. 32. E. Brown-Myrie, Pharm. D. Special Considerations – CAD Patients <ul><li>These patients are at high risk for CV morbidity and mortality </li></ul><ul><li>Avoid rapid lowering of BP esp. when reflex tachycardia and sympathetic stimulation occurs </li></ul><ul><li>CCBs and BBs are useful where angina is present with HTN but avoid short-acting CCBs </li></ul><ul><li>After MI, ACEIs, BBs and aldosterone antagonists have proven to be most beneficial </li></ul><ul><li>ACEIs are useful after an MI, esp. in LV dysfunction </li></ul><ul><li>Intensive lipid management and ASA therapy are also indicated </li></ul>
  33. 33. E. Brown-Myrie, Pharm. D. Special Considerations – CHF Patients <ul><li>Control of elevated BP improves myocardial function and prevents or reduces heart failure </li></ul><ul><li>ACEIs administered after an MI prevents subsequent heart failure and reduces morbidity and mortality </li></ul><ul><li>In CHF alone, ACEIs used alone or in combination with digoxin or diuretics reduce morbidity and mortality </li></ul>
  34. 34. E. Brown-Myrie, Pharm. D. Special Considerations – CHF Patients cont. <ul><li>ACEIs, BBs, ARBs and aldosterone inhibitors are recommended along with diuretics </li></ul><ul><li>Dihydropyridine CCBs e.g amlodipine and felodipine have been demonstrated to be safe in patients with angina, HTN and LV dysfunction </li></ul><ul><li>Hydralazine and ISDN can be used when ACEIs are not tolerated </li></ul>
  35. 35. E. Brown-Myrie, Pharm. D. Special Considerations – LV Hypertrophy <ul><li>LVH is a major risk factor for sudden cardiac death, MI, stroke and other CV events </li></ul><ul><li>All antihypertensive agents (except direct vasodilators), weight reduction and salt reduction reduce LV mass and wall thickness </li></ul>
  36. 36. E. Brown-Myrie, Pharm. D. Special Considerations – Peripheral Arterial Disease <ul><li>Data not available to determine if anti-hypertensive treatment alters the course of the disease. </li></ul><ul><li>Any class of drug may be used </li></ul>
  37. 37. E. Brown-Myrie, Pharm. D. Special Considerations – DM Patients <ul><li>Antihypertensive therapy should be initiated with lifestyle modification to achieve target goal of 130/80 mm Hg </li></ul><ul><li>Thiazide diuretics, ACEIs, alpha blockers, CCBs and ARBs are beneficial in reducing CVD and strokes in DM patients </li></ul><ul><li>ACEIs and ARBs are preferred in patients with diabetic nephropathy </li></ul>
  38. 38. E. Brown-Myrie, Pharm. D. Special Considerations – COPD or Asthma Patients <ul><li>BBs and alpha-beta blockers may exacerbate asthma </li></ul><ul><li>If asthma patient on ACEIs develop a cough, treat with ARBs </li></ul>
  39. 39. E. Brown-Myrie, Pharm. D. Special Considerations – Patients with Hyperlipidemia <ul><li>Lifestyle modifications should be employed </li></ul><ul><li>In high doses, thiazides and loop diuretics may produce increases in total cholesterol, TGs and LDL cholesterol </li></ul><ul><li>BBs may increase TGs transiently and increase HDL </li></ul><ul><li>ACEIs, ARBs, CCBs and alpha agonists have clinically neutral effects on lipids and lipoproteins </li></ul><ul><li>Aggressive treatment with statins provide protection against CHD </li></ul>
  40. 40. E. Brown-Myrie, Pharm. D. Special Considerations - Gout <ul><li>All diuretics can increase serum uric acid levels; rarely cause gout </li></ul><ul><li>Diuretic-induced hyper-uricemia does not require treatment in the absence of gout </li></ul>
  41. 41. E. Brown-Myrie, Pharm. D. Special Considerations – Patients with Renal Disease <ul><li>Aggressive management is desired to achieve target BP goal of 130/80 </li></ul><ul><li>Three or more drugs may be required to reach target BP </li></ul><ul><li>ACEIs and ARBs heve favorable effects on progression of diabetic and non-diabetic renal disease </li></ul><ul><li>Loop diuretics are usually required along with other drugs when GFR < 30 ml/min </li></ul>
  42. 42. E. Brown-Myrie, Pharm. D. Hypertensive Urgencies & Emergencies <ul><li>Associated with marked BP elevations (greater that 200/120 and/or evidence of optic disc edema and target organ complications </li></ul><ul><li>Urgencies – situations where BP is marked elevated but without acute target organ damage and reduction should take place within a few hours </li></ul><ul><li>Can be managed with oral doses of drugs which have fast onset of action </li></ul><ul><li>Examples include loop diuretics, BBs, ACEIs, alpha agonists or CCBs </li></ul>
  43. 43. E. Brown-Myrie, Pharm. D. Hypertensive Emergencies <ul><li>Require immediate blood pressure reduction to prevent or limit target organ damage </li></ul><ul><li>Examples include hypertensive encephalopathy, intracranial hemorrhage, unstable angina pectoris, AMI, aortic aneurysm and eclampsia </li></ul><ul><li>Initial treatment is usually with parenteral drugs eg. Nitroprusside, hydralazine, enalaprilat. </li></ul><ul><li>Goal is to reduce BP by 25% within minutes to 2 hours, then towards 160/100 within 2 to six hours </li></ul><ul><li>Use of sublingual nifedipine, though widely practised is associated with serious side effects and is unacceptable </li></ul><ul><li>BP should be monitored at 15 to 30 minute intervals </li></ul>
  44. 44. E. Brown-Myrie, Pharm. D. Resistant Hypertension <ul><li>Failure to achieve target BP goal despite adherence to appropriate therapy </li></ul><ul><li>Should explore reasons for failure (drug-induced causes, primary aldosteronism, renovascular disease, CRF, chronic steroid therapy </li></ul><ul><li>Consultation with hypertensive specialist should be considered </li></ul>
  45. 45. E. Brown-Myrie, Pharm. D. Medications used in Hypertension <ul><li>Diuretics – mainstay of therapy in most trials </li></ul><ul><li>3 types – thiazides, loop and potassium –sparing </li></ul><ul><li>Thiazides- effective in small doses (e.g HCTZ:12.5 to 25 mg) </li></ul><ul><li>All thiazide diuretics are equally effective in lowering BP </li></ul>
  46. 46. E. Brown-Myrie, Pharm. D. Loop Diuretics <ul><li>Bumetanide: 0.5 – 4 mg qd or bid </li></ul><ul><li>Furosemide: 40 – 240mg qd or bid </li></ul><ul><li>Torsemide: 5 – 100mg qd or bid </li></ul><ul><li>Ethacrynic acid: 25 – 100mg bid or tid </li></ul>
  47. 47. E. Brown-Myrie, Pharm. D. Potassium-sparing Diuretics <ul><li>Amiloride – may be used in combination products </li></ul><ul><li>Eplerenone – shown very good efficacy, particularly in blacks </li></ul><ul><li>Spironolactone – rarely used as antihypertensive </li></ul><ul><li>Triamterene - may be used in combination products </li></ul>
  48. 48. E. Brown-Myrie, Pharm. D. Alpha-1 receptor blockers <ul><li>Doxazosin </li></ul><ul><li>Prazosin </li></ul><ul><li>Terazosin </li></ul><ul><li>A beneficial effect of selective α 1 -receptor is that they provide symptomatic benefit to patients with benign prostatic hypertrophy </li></ul><ul><li>A potentially severe side effect is the first dose phenomenon </li></ul>
  49. 49. E. Brown-Myrie, Pharm. D. Alpha agonists <ul><li>Clonidine </li></ul><ul><li>Methyldopa </li></ul><ul><li>Chronic use results in sodium and water retention, especially with methyldopa. </li></ul><ul><li>Sedation and dry mouth are common side effects </li></ul><ul><li>These agents may cause depression, orthostatic hypotension and dizziness and rebound hypertension </li></ul>
  50. 50. E. Brown-Myrie, Pharm. D. Beta Blockers <ul><li>MOA: reduce BP by reducing cardiac output </li></ul><ul><li>Propranolol is the prototype </li></ul><ul><li>Pindolol and acebutalol have ISA. </li></ul><ul><li>Carvedilol has α and β blocking properties </li></ul><ul><li>Atenolol and nadolol have long half-life and are excreted renally </li></ul><ul><li>Adv. Effects: bradycardia, bronchospasm, AV conduction abnormalities </li></ul>
  51. 51. E. Brown-Myrie, Pharm. D. ACE Inhibitors <ul><li>Captopril, enalapril, lisinopril, Fosinopril, Quinapril, Prinivil, Ramipril, Benazepril </li></ul><ul><li>MOA: block production of angiotensin II, a potent vasoconstrictor </li></ul><ul><li>Captopril absorption is decreased 30 – 40% by food </li></ul><ul><li>Adv. Effects: cough, dysgeusia, hyperkalemia, skin rash, angioedema, proteinuria </li></ul>
  52. 52. E. Brown-Myrie, Pharm. D. Calcium Channel Blockers <ul><li>Verapamil, Diltiazem, Nifedipine, Isradipine, Nicardipine, Felodipine, Amlodipine </li></ul><ul><li>MOA: inhibit influx of extracellular calcium into smooth muscle cells and cause smooth muscle relaxation and vasodilation </li></ul><ul><li>Nifedipine cause greatest peripheral vasodilation; cause reflex tachycardia </li></ul><ul><li>Verapamil slows HR and AV conduction; diltiazem to a lesser extent </li></ul><ul><li>Other Adv.Effects: dizziness, flushing, HA, (Nif.); constipation is common with verapamil </li></ul>
  53. 53. E. Brown-Myrie, Pharm. D. Angiotensin II-Receptor Antagonists <ul><li>Losartan, valsartan, irbesartan, candesartan, telmisartan </li></ul><ul><li>MOA: Block the effects of angiotensin II at the receptor site </li></ul><ul><li>ARBs are well tolerated and are as effective as ACEIs in decreasing BP </li></ul><ul><li>Adv. Effects: dizziness, HA, GI disturbances </li></ul>
  54. 54. E. Brown-Myrie, Pharm. D. Vasodilators <ul><li>Hydralazine, Minoxidil </li></ul><ul><li>Cause direct arteriolar smooth muscle relaxation and vasodilation </li></ul><ul><li>Direct vasodilation can precipitate angina in patients with CAD, therefore use BBs </li></ul><ul><li>Use with BB and diuretic </li></ul><ul><li>Adv.Effects: SLE-like syndrome, HA, dermatitis, peripheral neuropathy (hydralazine); hypertrichosis from minoxidil </li></ul>
  55. 55. E. Brown-Myrie, Pharm. D. Postganglionic Sympathetic Inhibitors <ul><li>Guanethidine, guanadrel </li></ul><ul><li>MOA: deplete NE from PGS nerve terminals and inhibit NE release leading to decreased CO and TPR </li></ul><ul><li>Adv. Effects: postural hypotension, impotence, weight gain, GI complaints </li></ul><ul><li>Restricted to use in refractory HTN </li></ul>
  56. 56. E. Brown-Myrie, Pharm. D. RESERPINE <ul><li>MOA: depletes NE from sympathetic nerve endings and blocks transport into storage granules </li></ul><ul><li>Takes 2- 6 weeks for maximal effect </li></ul><ul><li>Causes significant Na and water retention </li></ul><ul><li>Unopposed parasympathetic activity results in nasal stuffiness, GI effects and bradycardia </li></ul><ul><li>Other Adv. Effects: depression, impotence </li></ul>
  57. 57. E. Brown-Myrie, Pharm. D. Imidazoline receptor binding drugs <ul><li>Example is Relminidine (Hyperium R ) </li></ul><ul><li>I 1 imidazoline selective agonist </li></ul><ul><li>acts by reducing sympathetic overactivity and inhibits renal sodium absorption </li></ul><ul><li>Selectivity for I 1 receptors over alpha 1 receptors provides the advantage of less central side effects (drowsiness, dry mouth) </li></ul>
  58. 58. E. Brown-Myrie, Pharm. D. COMBINATION PRODUCTS <ul><li>ACEIs and CCBs e.g amlodipine and benazepril (Lotrel) </li></ul><ul><li>ACEIs and Diuretics e.g. enalapril + HCTZ ( Vaseretic) </li></ul><ul><li>ARBs and Diuretics e.g.Losartan + HCTZ (Hyzaar) </li></ul><ul><li>BBs and Diuretics e.g.Atenolol + Chlorthalidone (Tenoretic) </li></ul><ul><li>Centrally acting drugs and Diuretics (methyldopa + HCTZ (Aldoril) </li></ul><ul><li>Diuretic and Diuretic e.g. amiloride + HCTZ (Moduretic) </li></ul>
  59. 59. New and Emerging Treatments for Hypertension <ul><li>Aliskiren ‐ a direct renin inhibitor </li></ul><ul><ul><li>Effective and safe but better than existing methods of RAAS inhibition? </li></ul></ul><ul><ul><li>Outcome studies needed! </li></ul></ul><ul><li>Nebivolol ‐ a 3rd generation ß‐blocker </li></ul><ul><ul><li>Effective and safe but better than other ß‐blockers? </li></ul></ul><ul><ul><li>Initial outcome study was positive but more are </li></ul></ul><ul><li>needed in patients with compelling indications </li></ul>E. Brown-Myrie, Pharm. D.
  60. 60. Aliskiren <ul><li>A highly specific direct renin inhibitor that reduces plasma renin activity (PRA) by 80% despite compensatory increases in plasma renin concentrations (PRC) </li></ul><ul><li>Poor oral bioavailability (≈ 2.5%) and food reduces AUC by 70% or more </li></ul><ul><li>Half‐life = 24 to 36 hours </li></ul><ul><li>Metabolized by CYP 3A4 and 25% is excreted unchanged in urine </li></ul><ul><li>No dosing adjustments needed based on age, hepatic or renal insufficiency </li></ul><ul><li>Gradman AH. J Am Coll Cardiol 2008; 51: 519‐28. Daughtery KK. AJHP 2008;65:1323-32 </li></ul>E. Brown-Myrie, Pharm. D.
  61. 61. What is Nebivolol <ul><li>Brand name Bystolic® </li></ul><ul><li>“ 3rd generation” highly selective ß1‐blocker with vasodilation induced by release of nitrous oxide </li></ul><ul><li>Does NOT have alpha blocking OR intrinsic sympathomimetic activity (ISA) </li></ul><ul><li>Racemic mixture </li></ul><ul><ul><li>l‐isomer: ß‐blocking activity </li></ul></ul><ul><ul><li>d‐isomer: nitrous oxide release </li></ul></ul><ul><li>􀁺 Extensive first pass metabolism </li></ul><ul><li>Veverka A. Ann Pharmacother 2006;40:1353‐60. Gray C. AJHP 2008; 65: 1125‐33. </li></ul>E. Brown-Myrie, Pharm. D.
  62. 62. E. Brown-Myrie, Pharm. D. Summary of JNC V11 Report <ul><li>Normal BP is < 120/80 </li></ul><ul><li>Prehypertension is 120-139/80-89 </li></ul><ul><li>Stage I is similar to JNC VI Report </li></ul><ul><li>Stage 2 incorporates stages 2 and 3 of Sixth Report </li></ul><ul><li>Treatment should consider presence or absence of compelling indications </li></ul><ul><li>Encourage healthy lifestyle for all individuals </li></ul>