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Antihypertensive Drug Update

Jessica Schwenk, Pharm.D. September 14, 2013. Antihypertensive Drug Update. Objectives. Review pharmacologic treatment of hypertension, including drug combinations and management of hypertension with other disease states Discuss updates in the use of antihypertensive drugs

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Antihypertensive Drug Update

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  1. Jessica Schwenk, Pharm.D. September 14, 2013 Antihypertensive Drug Update

  2. Objectives • Review pharmacologic treatment of hypertension, including drug combinations and management of hypertension with other disease states • Discuss updates in the use of antihypertensive drugs • Describe medications used for hypertensive urgencies and emergencies

  3. Review of Hypertension

  4. Review of Hypertension • How many people in the US have hypertension?

  5. Review of Hypertension • How many people in the US have hypertension? • 58 to 65 million adults (estimated in 2008) • 29-31% of US adults • Treatment of hypertension • #1 reason for doctor visits (non-pregnant adults) • #1 reason for use of prescription drugs

  6. Review of Hypertension • Definitions • Normal blood pressure: systolic <120 mmHg and diastolic <80 mmHg • Prehypertension: systolic 120-139 mmHg or diastolic 80-89 mmHg • Hypertension: • Stage 1: systolic 140-159 mmHg or diastolic 90-99 mmHg • Stage 2: systolic ≥160 or diastolic ≥100 mmHg

  7. Review of Hypertension • Definitions • Isolated systolic hypertension: systolic ≥140 mmHg and diastolic <90 mmHg • Isolated diastolic hypertension: systolic <140 mmHg and diastolic ≥90 mmHg

  8. Review of Hypertension • Definitions continued • Malignant hypertension: hypertension with retinal hemorrhages, exudates, or papilledema • Hypertensive encephalopathy • Acute renal failure • Hypertensive urgency: Diastolic blood pressure > 120 mmHg without symptoms

  9. Review of Hypertension • Primary (essential) hypertension • Pathogenesis  • Increased sympathetic neural activity (beta-adrenergic) • Increased angiotensin II activity • Mineralocorticoid excess • Genetics • Reduced adult nephron mass

  10. Review of Hypertension • Risk Factors • Ethnicity • Genetics • Diet • Sodium intake • Alcohol • Obesity • Tobacco use • Decreased physical activity • Hyperlipidemia • Age > 65 years • Personality Traits • Vitamin D Deficiency

  11. Review of Hypertension • Complications • Risk factor for other disease states • Heart failure • Left ventricular hypertrophy • Stroke • Intra-cerebral hemorrhage • Kidney disease • Malignant hypertension

  12. Review of Hypertension • Treatment benefits • Reduce risk of cardiovascular events, kidney disease, eye damage, morbidity and mortality • Only 46-51%have blood pressure under control • Poor access to healthcare, medications • Lack of adherence • Side effects, disadvantages of therapy • Benefits not obvious to patients

  13. Treatment of Hypertension Lifestyle Modifications Treatment Algorithm Treatment Goal Medication Classes

  14. Treatment of Hypertension • Lifestyle Modification

  15. Treatment Goal • JNC7 blood pressure goals • Generally <140/<90 mmHg • Complications or increased risk factors <130/<90 • Diabetes • Chronic kidney disease

  16. Treatment of Hypertension • Medications • Monitor • Blood pressure • Side effects: hypotension, orthostatic hypotension, dizziness

  17. Thiazide Diuretics • Chlorthalidone (generic) 12.5-25 mg daily • Hydrochlorothiazide (Microzide, HydroDIURIL) 12.5-50 mg daily • Indapamide (Lozol) 1.25-2.5 mg daily • Metolazone (Zaroxolyn) 2.5-5 mg daily

  18. Thiazide Diuretics • Side effects • Hypokalemia • Hypomagnesemia • Hypercalcemia • Hyperuricemia • Hyperglycemia • Hyperlipidemia • Sexual dysfunction • Monitoring • Fluid status • Electrolytes • Renal function • Loses efficacy with ClCr < 40 mL/min • Dose-related side effects • Limiting dose to chlorthalidone or HCTZ 25-50 mg greatly reduces risk of metabolic side effects

  19. Loop Diuretics • Bumetanide (Bumex) 0.5-2 mg daily-BID • Furosemide (Lasix) 20-80 mg daily-BID • Torsemide (Demadex) 2.5-10 mg daily

  20. Loop Diuretics • Side Effects • Hypokalemia • Hypomagnesemia • Hypocalcemia • Hyperuricemia • Sexual dysfunction • Monitoring • Fluid status • Weight loss/gain • Electrolytes • Usually need electrolyte supplementation • Renal function • Hearing (high doses)

  21. Potassium-Sparing Diuretics • Amiloride (Midamor) 5-10 mg daily-BID • Triamterene (Dyrenium) 50-100 mg daily-BID Aldosterone Antagonists • Eplerenone (Inspra) 50-100 mg daily • Spironolactone (Aldactone) 25-50 mg daily

  22. Potassium-Sparing Diuretics/Aldosterone Antagonists • Side effects • Similar to thiazide diuretics: hypomagnesemia, hypercalcemia, hyperuricemia, sexual dysfunction • Hyperkalemia • Especially eplerenone (contraindicated in impaired renal function or DM II with proteinuria) • Gynecomastia (10% with spironolactone) • Monitoring • Electrolytes, fluid status, renal function

  23. Angiotensin Converting Enzyme (ACE) Inhibitors • Benazepril (Lotensin) 10-40 mg daily • Captopril (Capoten) 25-100 mg BID • Enalapril (Vasotec) 5-40 mg daily-BID • Fosinopril (Monopril) 10-40 mg daily • Lisinopril (Prinivil, Zestril) 10-40 mg daily • Moexipril (Univasc) 7.5-30 mg daily • Perindopril (Aceon) 4-8 mg daily • Quinapril (Accupril) 10-80 mg daily • Ramipril (Altace) 2.5-20 mg daily • Trandolapril (Mavik) 1-4 mg daily

  24. Angiotensin Converting Enzyme (ACE) Inhibitors • Side effects • Hyperkalemia • Dry cough (20%) • Increased serum creatinine/kidney insufficiency • Angioedema (2%) • Rare (<1%) • Neutropenia and agranulocytosis, proteinuria, glomerulonephritis, acute kidney failure • Monitoring: potassium, kidney function • Absolute contraindication in pregnancy

  25. Angiotensin II Receptor Blockers (ARBs) • Candesartan (Atacand) 8-32 mg daily • Eprosartan (Teveten) 400-800 mg daily-BID • Irbesartan (Avapro) 150-300 mg daily • Losartan (Cozaar) 25-100 mg daily-BID • Olmesartan (Benicar) 20-40 mg daily • Telmisartan (Micardis) 20-80 mg daily • Valsartan (Diovan) 80-320 mg daily-BID

  26. Angiotensin II Receptor Blockers (ARBs) • Side effects • Hyperkalemia • Increased serum creatinine/kidney insufficiency • Possible angioedema (cross-reactivity with ACEIs reported) • No bradykinin-induced dry cough • Monitoring: potassium, kidney function • Should not be used in pregnancy

  27. Calcium Channel Blockers • Non-Dihydropyridines • Diltiazem • Extended release (Cardizem CD, Dilacor XR, Tiazac) 180-420 mg daily • Extended release (Cardizem LA) 120-540 mg dialy • Verapamil • Immediate release (Calan, Isoptin†) 80-320 mg BID • Long acting (Calan SR, Isoptin SR†) 120-480 mg daily-BID, (Coer, Covera HS, Verelan PM) 120-360 mg daily

  28. Calcium Channel Blockers • Dihydropyridines • Amlodipine (Norvasc) 2.5-10 mg daily • Felodipine (Plendil) 2.5-20 mg daily • Isradipine (Dynacirc CR) 2.5-10 mg daily • Nicardipine sustained release (Cardene SR) 60-120 mg BID • Nifedipinelong-acting (Adalat CC, Procardia XL) 30-60 mg daily • Nisoldipine (Sular) 10-40 mg daily

  29. Calcium Channel Blockers • Side effects • Flushing, headache, gingival hyperplasia, peripheral edema • Non-dihydropyridines: bradycardia, AV block (high doses), heart failure, anorexia • Precautions/Contraindications • Contraindicated in heart failure • Multiple drug interactions due to CYP450 3A4 inhibition • Combination of non-dihydropyridine with beta blocker increases chance of heart block

  30. Beta Blockers • Beta-1 selective (cardioselective) • Atenolol (Tenormin) 25-100 mg daily • Metoprolol (Lopressor, Toprol XL) 50-100 mg daily-BID • Betaxolol (Kerlone) 5-10 mg daily • Bisaprolol (Zebeta) 2.5-20 mg daily • Non-selective • Nadolol (Corgard) 40-120 mg daily • Propranolol (Inderal, Inderal LA) 40-160 mg BID (60-180 mg daily for LA) • Timolol (Blocadren) 20-40 mg BID

  31. Beta Blockers • Intrinsic sympathomimetic activity • Acebutolol (Sectral) 200-800 mg BID • Penbutolol (Levatol) 10-40 mg daily • Pindolol (generic) 10-40 mg BID • Combined alpha-1 and beta blockers • Carvedilol (Coreg) 12.5-50 mg BID • Labetalol (Normodyne, Trandate†) 200-800 mg BID • Nebivolol (Bystolic) 5-40 mg daily

  32. Beta Blockers • Side effects • Bradycardia, heart block, heart failure • Monitoring: HR • Increased blood glucose • Sexual dysfunction (impotence) • Abrupt cessation: rebound hypertension, unstable angina/myocardial infarction • Specific groups • More CNS effects (dizziness/drowsiness ) with more lipophylic agents (propranolol) • Non-selective agents: β2-receptor activation, bronchospasm • Non-ISA agents: increased triglycerides

  33. Alpha-1 Blockers • Doxazosin (Cardura) 1-16 mg daily • Prazosin (Minipress) 2-20 mg BID-TID • Terazosin (Hytrin) 1-20 mg daily-BID • Side effects • 1st dose phenomenon: dizziness, palpitations, syncope • Orthostatic hypotension • CNS effects: vivid dreams, depression • Sodium and water retention

  34. Central alpha-2 agonists and Other centrally acting drugs • Clonidine (Catapres) 0.1-0.8 mg BID • Clonidine patch (Catapres-TTS) 0.1-0.3 weekly • Clonidine (Catapres) 0.1-0.8 mg BID • Methyldopa (Aldomet†) 250-1,000 mg BID • Reserpine (generic) 0.1-0.25 mg daily • Guanfacine (Tenex†) 0.5-2 mg daily

  35. Central alpha-2 agonists and Other centrally acting drugs • Side effects • Sodium and water retention • Orthostatic hypotension • CNS side effects: depression • Anticholinergic: dry mouth, sedation, constipation, urinary retention, blurred vision • Reserpine: parasympathetic activity (increased secretions, bradycardia) • Abrupt cessation: rebound hypertension • Clonidine often used for resistant hypertension • Methyldopa is a first-line agent in pregnancy

  36. Direct vasodilators • Hydralazine (Apresoline) 25-100 mg BID • Minoxidil (Loniten) 2.5-80 mg daily-BID • Side effects • Sodium and water retention • Tachyphylaxis (use with beta blocker) • Hydralazine • Lupus-like syndrome, dermatitis, drug fever, peripheral neuropathy, hepatitis, vascular HA • Minoxidil • Hypertrichosis(hirsutism of face, arms, back, chest), pericardial effusion, nonspecific T-wave change

  37. Treatment of Hypertension Treatment of hypertension with concurrent disease states or compelling indications Choice of medication for hypertension Treatment of hypertensive urgency & emergency New Recommendations

  38. Ischemic Heart Disease • Stable angina • Beta blocker, or CCB • Acute coronary syndrome • Beta blocker (without ISA), ACEI • Post-MI • Beta blocker, ACEI, aldosterone antagonist

  39. Heart Failure • Asymptomatic heart failure • ACEI (or ARB), beta blocker • Symptomatic ventricular dysfunction or end-stage heart disease • Beta blocker, ACEI or ARB, aldosterone antagonist, loop diuretic

  40. Diabetes • ACEI or ARB • Reduce diabetic nephropathy and albuminuria • ARBs reduce progression to macroalbuminuria • Thiazide diuretics, BBs, ACEIs, ARBs, and CCBs • Prevent CVD and stroke incidence • Caution with beta blockers • Mask signs of hypoglycemia

  41. Chronic Kidney Disease • ACEI or ARB • Slow progression of renal disease • Limited rise in Scr acceptable (up to 35% increase) • Advanced CKD • Loop diuretics (volume control) • Thiazide diuretics lose efficacy with ClCr < 40

  42. Cerebrovascular Disease • Combination of thiazide diuretic and ACEI • Reduce recurrent stroke rate

  43. Left ventricular hypertrophy • All classes of antihypertensive agents except the direct vasodilators hydralazine and minoxidil • Regression of LVH • Severe hypertension with ECG evidence of LVH • ARB • Only indication where ARB has proven benefit over ACEI

  44. Ethnicity • African-American • Monotherapy: thiazide diuretic or CCB • Reduced BP responses with BBs, ACEIs, or ARBs • Caution: ACEI-induced angioedema occurs 2–4 times more frequently • Heart failure • Hydralazine/Isosorbidedinitrate (Bidil)

  45. Elderly • Follow same principles of therapy • Start at lower doses, increase more slowly • Avoid side effects • Classes to avoid • Alpha-1 blockers, alpha-2 agonists, centrally acting agents, direct vasodilators • Treatment of HTN may slow progression of cognitive impairment and dementia

  46. Pregnancy • Preferred agents • Methyldopa, beta blockers, and vasodilators • Contraindicated: • ACEIs and ARBs

  47. Other indications • Atrial tachyarrythmias/fibrillation • Beta blockers or calcium channel blockers (rate control) • Migraine, tremor • Beta blockers • BPH • Alpha-1 blockers • Asthma, reactive airway disease, second or third degree heart block • Avoid beta-blockers (especially non-selective) • Gout, hyponatremia • Avoid thiazide diuretics • Hyperkalemia • Avoid potassium-sparing diuretics, aldosterone antagonists

  48. Choice of initial medication

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