Treatment Guidelines from The Medical Letter® Published by The Medical Letter • 145 Huguenot Street, New Rochelle, NY 10801 • A Nonprofit Publication IN THIS ISSUE (starts on next page) Drugs for Hypertension p 31 The Medical Letter ® publications are protected by US and international copyright laws Forwarding, copying or any distribution of this material is prohibited Sharing a password with a non-subscriber or otherwise making the contents of this site available to third parties is strictly prohibited By accessing and reading the attached content I agree to comply with US and international copyright laws and these terms and conditions of The Medical Letter, Inc For further information click: Subscriptions, Site Licenses, Reprints or call customer service at: 800-211-2769 FORWARDING OR COPYING IS A VIOLATION OF US AND INTERNATIONAL COPYRIGHT LAWS Revised 6/24/14: See page 37 The Medical Letter publications are protected by US and international copyright laws Forwarding, copying or any other distribution of this material is strictly prohibited For further information call: 800-211-2769 Treatment Guidelines from The Medical Letter® Published by The Medical Letter • 145 Huguenot Street, New Rochelle, NY 10801 • A Nonprofit Publication Volume 12 (Issue 141) May 2014 www.medicalletter.org Take CME exams Drugs for Hypertension Tables Initial Monotherapy Diuretics Renin-Angiotensin System Inhibitors Calcium Channel Blockers Beta-Adrenergic Blockers Alpha-Adrenergic Blockers and Other Antihypertensives Some Combination Products Page 31 Page 32 Page 33 Page 34 Page 35 Page 36 Page 37 Related article(s) since publication RECOMMENDATIONS: Nearly all recent guidelines recommend a thiazide-type diuretic (chlorthalidone is preferred), a calcium channel blocker, an angiotensinconverting enzyme (ACE) inhibitor, or an angiotensin receptor blocker (ARB) as initial therapy for the general population of hypertensive patients.1-6 For black patients, a thiazide-type diuretic or calcium channel blocker is recommended for initial therapy, except for those with chronic kidney disease or heart failure, who should receive an ACE inhibitor or an ARB.7 Beta blockers generally are no longer recommended as initial therapy except for patients with another indication, such as coronary heart disease or left ventricular dysfunction Most guidelines recommend an ACE inhibitor or an ARB over other classes for initial treatment of hypertension in non-black patients with diabetes.8 Many patients with hypertension need more than one drug to control their BP Generally, if the first drug does not achieve BP goals, adding a second drug with a different mechanism of action is more effective in decreasing BP than increasing the dose of the first drug and often allows for use of lower, better tolerated doses of both drugs If an ACE inhibitor or an ARB was used initially, it would be reasonable to add a diuretic such as chlorthalidone or a calcium channel blocker Two renin-angiotensin system inhibitors should not be used together When baseline BP is >20/10 mm Hg above goal, many experts would begin therapy with drugs Most recent guidelines recommend a BP goal of 140/90 mm Hg.1,2,4,6 For patients >60 years old without diabetes or chronic kidney disease, one guideline recommends 150/90 mm Hg both as the drug treatment initiation threshold and treatment target4; this higher target is controversial, except in patients >80 years old.9 Drugs available for treatment of chronic hypertension in the US and their dosages and adverse effects are listed in the tables that begin on page 32 Combination products are listed on page 37 Drugs for treatment of hypertensive emergencies are not discussed here Table Initial Monotherapy General Population Non-black Black THZD, ACE inhibitor, ARB, or CCB THZD or CCB Chronic Kidney Disease (CKD) Non-black Black ACE inhibitor or ARB ACE inhibitor or ARB Diabetes Non-black Black ACE inhibitor or ARB THZD or CCB* THZD = thiazide-type diuretic; ACE = angiotensin-converting enzyme; ARB = angiotensin receptor blocker; CCB = calcium channel blocker * Black patients with both diabetes and CKD should receive an ACE inhibitor or an ARB DIURETICS Thiazide-type diuretics are used for initial treatment of many patients with hypertension Most studies that have shown outcome benefits of thiazide-type diuretics have used chlorthalidone and found it at least as effective as other antihypertensive agents in reducing cardiovascular and renal risk and superior in preventing heart failure.10,11 Chlorthalidone is more potent than hydrochlorothiazide, has a longer duration of action that persists throughout the nighttime hours, and has been shown to be more effective.12 Metolazone may be effective in patients with impaired renal function when the other thiazides are not, but outcomes data are lacking In one study in patients >80 years old, indapamide, with or without the ACE inhibitor perindopril, reduced the incidence of death from stroke or any cause.13 Loop diuretics such as furosemide are used instead of thiazides to lower BP in patients with moderate to severe renal impairment In patients with normal renal function, they are less effective than thiazides for treatment of hypertension Ethacrynic acid can be used for patients allergic to sulfonamides (thiazide and loop diuretics other than ethacrynic acid contain sulfonamide moieties) Federal copyright law prohibits unauthorized reproduction by any means and imposes severe fines 31 Drugs for Hypertension Table Diuretics1 Some Available Oral Formulations Drug Usual Maintenance Dosage2 Pregnancy Category3 Frequent or Severe Adverse Effects4 Cost5 Thiazide-Type Chlorthalidone – generic 25, 50 mg tabs Chlorothiazide – generic 250, 500 mg tabs Diuril (Salix) 250 mg/5 mL susp Hydrochlorothiazide – generic 12.5 mg caps; 12.5, 25, 50 mg tabs Microzide (Actavis) 12.5 mg caps Indapamide – generic 1.25, 2.5 mg tabs Metolazone – generic Zaroxolyn (UCB) 2.5, mg tabs 12.5-25 mg once/d B 125-500 mg once/d 12.5-50 mg once/d C 1.25-2.5 mg once/d 2.5-5 mg once/d B B $ 6.60 Hyperuricemia, hypokalemia, hypomagnesemia, hyperglycemia, hyponatremia, hypercalcemia, hypercholesterolemia, hypertriglyceridemia, pancreatitis, rash and other allergic reactions, photosensitivity reactions B 2.60 16.70 8.40 35.10 6.90 24.70 83.10 Loop Bumetanide* – generic Ethacrynic acid* – Edecrin (Valeant) Furosemide – generic Lasix (Sanofi) Torsemide – generic Demadex (Meda) 0.5, 1, mg tabs 0.5-2 mg once/d or divided bid 25 mg tabs 50-200 mg once/d or divided bid 20, 40, 80 mg tabs; 20-80 mg once/d 10 mg/mL, 40 mg/5 mL soln or divided bid 20, 40, 80 mg tabs 5, 10, 20, 100 mg tabs 5-10 mg once/d C B C B 13.40 Dehydration, circulatory collapse, hypokalemia, hyponatremia, hypomagnesemia, hyperglycemia, metabolic alkalosis, hyperuricemia, blood dyscrasias, rash, hypercholesterolemia, hypertriglyceridemia 484.20 1.20 13.20 9.00 53.10 Potassium-Sparing Amiloride – generic mg tabs 5-10 mg once/d B Hyperkalemia, GI disturbances, rash, headache Hyperkalemia, GI disturbances, nephrolithiasis Triamterene* – Dyrenium (WellSpring) 50, 100 mg caps 50-150 mg once/d or divided bid C 25, 50 mg tabs 50 mg once/d or bid 50-100 mg once/d or divided bid B Hyperkalemia, hyponatremia C Hyperkalemia, hyponatremia, mastodynia, gynecomastia, menstrual abnormalities, GI disturbances, rash 23.90 99.60 Aldosterone Antagonists Eplerenone – generic Inspra (Pfizer) Spironolactone – generic Aldactone (Pfizer) 25, 50, 100 mg tabs 94.20 174.60 6.20 68.10 * Not FDA-approved for treatment of hypertension Diuretics are not recommended for treatment of gestational hypertension Dosage adjustments may be needed for renal or hepatic impairment FDA pregnancy categories: A = controlled studies show no risk; B = no evidence of risk in animals; no human studies; C = risk cannot be ruled out; D = positive evidence of risk; X = contraindicated during pregnancy Class effects Some may not have been reported with every drug in the class In addition to the adverse effects listed, antihypertensive drugs may interact adversely with other drugs Approximate wholesale acquisition cost (WAC) for 30 days’ treatment at the lowest recommended dosage Source: Analy$ource® Monthly (Selected from FDB MedKnowledge™) April 5, 2014 Reprinted with permission by FDB, Inc All rights reserved ©2014 www.fdbhealth.com/policies/drug-pricing-policy Actual retail prices may be higher Potassium-sparing diuretics such as amiloride and triamterene are generally used with other diuretics to prevent or correct hypokalemia These drugs can cause hyperkalemia, particularly in patients with renal impairment and in those taking ACE inhibitors, ARBs, beta blockers, or aliskiren Spironolactone, a mineralocorticoid receptor antagonist also used as a potassium-sparing diuretic, has been effective as an add-on in patients with refractory hypertension.14 Eplerenone, a selective mineralocorticoid receptor antagonist that is also effective as an add-on in patients with refractory hypertension, is less likely to cause gynecomastia than high doses of spironolactone Both spironolactone and eplerenone have been shown to reduce the risk of death in patients with heart failure when added to standard therapy.15 32 ANGIOTENSIN-CONVERTING ENZYME (ACE) INHIBITORS ACE inhibitors are effective in treating hypertension and are generally well tolerated They are less effective in black patients and in those with low-renin hypertension, unless combined with a thiazide-type diuretic or calcium channel blocker, in which case the combined effect is similar to that in non-black patients ACE inhibitors have been shown to prolong survival in patients with heart failure or left ventricular dysfunction after a myocardial infarction, reduce mortality in patients without heart failure or left ventricular dysfunction who are at high risk for cardiovascular events, and reduce proteinuria in patients with either diabetic or non-diabetic nephropathy They should not be used during pregnancy Treatment Guidelines from The Medical Letter • Vol 12 (Issue 141) • May 2014 Drugs for Hypertension Table Renin-Angiotensin System Inhibitors Some Available Oral Formulations Drug Usual Maintenance Dosage1 Pregnancy Category2,3 Frequent or Severe Adverse Effects4 Cost5 Angiotensin-Converting Enzyme (ACE) Inhibitors Benazepril – generic Lotensin (Novartis) Captopril – generic 5, 10, 20, 40 mg tabs 12.5, 25, 50, 100 mg tabs 2.5, 5, 10, 20 mg tabs Enalapril – generic Vasotec (Valeant) Fosinopril – generic 10, 20, 40 mg tabs Lisinopril – generic Zestril (AstraZeneca) Prinivil (Merck) 2.5, 5, 10, 20, 30, 40 mg tabs 5, 10, 20 mg tabs Moexipril – generic Univasc (UCB) Perindopril – generic Aceon (Xoma) Quinapril – generic Accupril (Pfizer) Ramipril – generic Altace (Pfizer) Trandolapril – generic Mavik (Abbvie) 7.5, 15 mg tabs 2, 4, mg tabs 5, 10, 20, 40 mg tabs 1.25, 2.5, 5, 10 mg caps 1, 2, mg tabs 20-80 mg once/d or divided bid 25-50 mg bid or tid D D 2.5-40 mg once/d or divided bid 10-80 mg once/d or divided bid 10-40 mg once/d D 7.5-30 mg once/d or divided bid 4-8 mg once/d or divided bid 10-80 mg once/d or divided bid 2.5-20 mg once/d or divided bid 1-8 mg once/d or divided bid D D D D D Cough, hypotension (particularly with diuretic use or volume depletion), rash, acute renal failure in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, angioedema, hyperkalemia (particularly if also taking potassium supplements or potassium-sparing diuretics), mild to moderate loss of taste, hepatotoxicity, pancreatitis, blood dyscrasias and renal damage (particularly in patients with renal dysfunction) D D $ 3.60 57.30 22.80 3.00 135.50 7.80 2.80 39.60 38.10 27.00 78.00 19.80 73.20 20.70 74.10 5.70 91.20 12.00 52.50 Angiotensin Receptor Blockers (ARBs) Azilsartan – Edarbi (Arbor) 40, 80 mg tabs Candesartan – generic 4, 8, 16, 32 mg tabs Atacand (AstraZeneca) Eprosartan – generic 400, 600 mg tabs Teveten (Abbvie) Irbesartan – generic 75, 150, 300 mg tabs Avapro (Sanofi) Losartan – generic 25, 50, 100 mg tabs Cozaar (Merck) Olmesartan – Benicar 5, 20, 40 mg tabs (Daiichi Sankyo) Telmisartan – generic 20, 40, 80 mg tabs Micardis (Boehringer Ingelheim) Valsartan – Diovan (Novartis) 40, 80, 160, 320 mg tabs 80 mg once/d 8-32 mg once/d or divided bid 400-800 mg once/d or divided bid 150-300 mg once/d D D D 25-100 mg once/d or divided bid 20-40 mg once/d D D 20-80 mg once/d D 80-320 mg once/d D 150-300 mg once/d D Similar to ACE inhibitors; seldom cause cough, rarely cause angioedema and rhabdomyolysis 118.00 77.60 88.10 82.20 98.10 12.70 106.00 3.60 63.90 106.80 115.70 147.20 129.00 Direct Renin Inhibitor (DRI) Aliskiren – Tekturna (Novartis) 150, 300 mg tabs Same as ARBs, but can also cause GI effects such as diarrhea 115.30 Dosage adjustments may be needed for renal or hepatic impairment ACE inhibitors, ARBs, and aliskiren are classified as category D during the second and third trimesters Drugs that act on the renin-angiotensin system can cause fetal and neonatal morbidity and death FDA pregnancy categories: A = controlled studies show no risk; B = no evidence of risk in animals; no human studies; C = risk cannot be ruled out; D = positive evidence of risk; X = contraindicated during pregnancy In addition to the adverse effects listed, antihypertensive drugs may interact adversely with other drugs Approximate wholesale acquisition cost (WAC) for 30 days’ treatment at the lowest recommended dosage Source: Analy$ource® Monthly (Selected from FDB MedKnowledge™) April 5, 2014 Reprinted with permission by FDB, Inc All rights reserved ©2014 www.fdbhealth.com/policies/drug-pricing-policy Actual retail prices may be higher ANGIOTENSIN RECEPTOR BLOCKERS (ARBs) ARBs are as effective as ACE inhibitors in lowering BP, and appear to be at least equally renal and cardiac protective, with fewer adverse effects Like ACE inhibitors, they are less effective in black patients and in those with low-renin hypertension, unless combined with a thiazide-type diuretic or calcium channel blocker ARBs should not be used during pregnancy DIRECT RENIN INHIBITOR Aliskiren, a direct renin inhibitor, is FDA-approved alone or in combination with other antihypertensive drugs for treatment of hypertension.16 Whether aliskiren offers any advantage over ACE inhibitors or ARBs remains to be determined, and no outcomes data are available for aliskiren A randomized trial (ALTITUDE) evaluating the addition of aliskiren to an ACE inhibitor or an ARB in patients with type diabetes and chronic Treatment Guidelines from The Medical Letter • Vol 12 (Issue 141) • May 2014 33 Drugs for Hypertension Table Calcium Channel Blockers Drug Some Available Oral Formulations Usual Maintenance Dosage1 2.5, 5, 10 mg tabs 2.5-10 mg once/d C 2.5, 5, 10 mg ER tabs 2.5, mg caps 20, 30 mg caps 2.5-10 mg once/d 5-10 mg divided bid 60-120 mg divided tid C C C 30, 60 mg ER caps 60-120 mg divided bid Pregnancy Category2 Frequent or Severe Adverse Effects3 Cost4 Dihydropyridines Amlodipine5 – generic Norvasc (Pfizer) Felodipine – generic Isradipine – generic Nicardipine – generic extended-release Cardene SR (EKR) Nifedipine6 – extended-release generic Adalat CC (Bayer) Procardia XL (Pfizer) Nisoldipine – generic Sular (Shionogi) C 30, 60, 90 mg ER tabs 30-90 mg once/d 8.5, 17, 20, 25.5, 30, 34, 40 mg ER tabs 8.5, 17, 34 mg ER tabs 17-34 mg once/d 180, 240, 300, 360, 420 mg ER tabs 120, 180, 240, 300, 360, 420 mg ER tabs 120, 180, 240, 300, 360 mg ER caps 120-540 mg once/d Dizziness, headache, peripheral edema (more than with verapamil and diltiazem, more common in women), flushing, tachycardia, rash, gingival hyperplasia C $ 4.80 94.50 32.40 42.30 58.50 99.70 27.90 42.30 94.20 182.70 396.90 Non-Dihydropyridines Diltiazem6 generic (extended-release) Cardizem LA (Abbvie) generic (extended-release) Taztia XT (Actavis) Tiazac (Valeant) generic (continuous-delivery) 120, 180, 240, 300, Cardizem CD (Valeant) 360 mg ER caps Cartia XT (Actavis) Dilt-CD (Apotex) Verapamil (extended-release) generic (tabs) 120, 180, 240 mg ER tabs generic (caps) 120, 180, 240, 360 mg ER caps Calan SR (Pfizer) 120, 180, 240 mg SR tabs extended-release (once/d) Covera-HS (Pfizer) 180, 240 mg ER tabs Verelan (Elan) 120, 180, 240, 360 mg generic SR caps Verelan PM (Elan) 100, 200, 300 mg ER caps generic C 106.77 114.10 120-540 mg once/d 180-360 mg once/d 120-480 mg once/d or divided bid C Dizziness, headache, edema, constipation (especially verapamil), AV block, bradycardia, heart failure, lupus-like rash with diltiazem 19.40 24.40 39.30 27.30 320.30 27.90 27.90 23.30 24.00 93.30 180-480 mg once/d 120-480 mg once/d 200-400 mg once/d 64.20 144.30 22.80 150.60 60.30 ER = extended-release; SR = sustained-release Dosage adjustments may be needed for renal or hepatic impairment FDA pregnancy categories: A = controlled studies show no risk; B = no evidence of risk in animals; no human studies; C = risk cannot be ruled out; D = positive evidence of risk; X = contraindicated during pregnancy In addition to the adverse effects listed, antihypertensive drugs may interact adversely with other drugs Approximate wholesale acquisition cost (WAC) for 30 days’ treatment at the lowest recommended dosage Source: Analy$ource® Monthly (Selected from FDB MedKnowledge™) April 5, 2014 Reprinted with permission by FDB, Inc All rights reserved ©2014 www.fdbhealth.com/policies/drug-pricing-policy Actual retail prices may be higher Amlodipine is also available in combination with atorvastatin (Caduet, and generics) Immediate-release formulation is not recommended for treatment of hypertension Dilacor XR (Actavis) is also available in 120, 180, 240 mg ER capsules Also available in 420 mg ER caps Not available in 360 mg ER caps kidney disease was terminated prematurely due to an increase in adverse cardiovascular and renal events with the combination.17,18 Like ACE inhibitors and ARBs, aliskiren should not be used during pregnancy CALCIUM CHANNEL BLOCKERS Calcium channel blockers are a structurally and functionally heterogeneous class of drugs They all cause vasodilation and decrease total peripheral resistance The cardiac response to decreased vascular resistance is variable; with some dihydropyridines (felodipine, 34 nicardipine, nisoldipine, and immediate-release nifedipine), an initial reflex tachycardia usually occurs, but isradipine, sustained-release nifedipine, and amlodipine generally have less effect on heart rate The non-dihydropyridines verapamil and diltiazem slow heart rate, can slow atrioventricular (AV) conduction, and should be used with caution in patients who are also taking a beta blocker In one meta-analysis, the risk of heart failure was higher in patients treated with calcium channel blockers than in those treated with ACE inhibitors, beta blockers, Treatment Guidelines from The Medical Letter • Vol 12 (Issue 141) • May 2014 Drugs for Hypertension Table Beta-Adrenergic Blockers Drug Atenolol – generic Tenormin (AstraZeneca) Betaxolol5 – generic Bisoprolol5 – generic Zebeta (Teva) Metoprolol5 – generic extended-release generic Toprol-XL (AstraZeneca) Nadolol – generic Corgard (Pfizer) Propranolol – generic extended-release generic Inderal LA (Akrimax) InnoPran XL (GSK) Timolol – generic Some Available Oral Formulations Usual Maintenance Dosage1 25, 50, 100 mg tabs 50-100 mg once/d Pregnancy Category2 D 10, 20 mg tabs 5, 10 mg tabs 5-20 mg once/d 5-20 mg once/d C C 25, 50, 100 mg tabs 100-450 mg divided bid or tid C 25, 50, 100, 200 mg ER tabs 25-400 mg once/d 20, 40, 80 mg tabs 40-320 mg once/d C 10, 20, 40, 60, 80 mg tabs 80-240 mg divided bid C 60, 80, 120, 160 mg ER caps 80, 120 mg ER caps 5, 10, 20 mg tabs 60-240 mg once/d 80-120 mg once/d 20-60 mg divided bid Frequent or Severe Adverse Effects3 Fatigue, depression, bradycardia, erectile dysfunction, decreased exercise tolerance, heart failure, worsening of peripheral arterial insufficiency, may aggravate allergic reactions, bronchospasm, may mask symptoms of and delay recovery from hypoglycemia, Raynaud’s phenomenon, insomnia, vivid dreams or hallucinations, acute mental disorder, increased serum triglycerides, decreased HDL cholesterol, increased incidence of diabetes, sudden withdrawal may lead to exacerbation of angina and myocardial infarction or precipitate thyroid storm C Cost4 $ 1.50 47.10 12.80 25.50 134.90 2.40 22.00 35.70 95.60 117.90 3.60 47.00 315.60 395.30 39.60 Beta Blockers with Intrinsic Sympathomimetic Activity Acebutolol5 – generic Sectral (Promius) 200, 400 mg caps 200-1200 mg once/d or divided bid B Penbutolol – Levatol (Auxilium) 20 mg tabs 10-80 mg once/d C Pindolol – generic 5, 10 mg tabs 10-60 mg divided bid B 3.125, 6.25, 12.5, 25 mg tabs 12.5-50 mg divided bid C 10, 20, 40, 80 mg ER caps 100, 200, 300 mg tabs 20-80 mg once/d Similar to other beta-adrenergic blocking drugs, but with less resting bradycardia and lipid changes; acebutolol has been associated with a positive antinuclear antibody test and occasional drug-induced lupus 8.10 108.60 50.85 52.20 Beta Blockers with Alpha-Blocking Activity Carvedilol – generic Coreg (GSK) extended-release Coreg CR (GSK) Labetalol – generic Trandate (Prometheus) 200-1200 mg divided bid C Similar to other beta-adrenergic blocking drugs, but more orthostatic hypotension; hepatotoxicity with labetalol 100, 200 mg tabs 6.40 159.60 160.70 21.00 37.20 Beta Blockers with Vasodilating Nitric Oxide-Mediated Activity Nebivolol – Bystolic (Forest) 2.5, 5, 10, 20 mg tabs 5-40 mg once/d C Similar to other beta-adrenergic blocking drugs, but may not cause impotence, and may improve erectile dysfunction 78.70 ER = extended-release Dosage adjustments may be needed for renal or hepatic impairment FDA pregnancy categories: A = controlled studies show no risk; B = no evidence of risk in animals; no human studies; C = risk cannot be ruled out; D = positive evidence of risk; X = contraindicated during pregnancy In addition to the adverse effects listed, antihypertensive drugs may interact adversely with other drugs Approximate wholesale acquisition cost (WAC) for 30 days’ treatment at the lowest recommended dosage Source: Analy$ource® Monthly (Selected from FDB MedKnowledge™) April 5, 2014 Reprinted with permission by FDB, Inc All rights reserved ©2014 www.fdbhealth.com/policies/drug-pricing-policy Actual retail prices may be higher Cardioselective or diuretics.19 However, in one large outcomes trial (ACCOMPLISH), the ACE inhibitor benazepril plus the calcium channel blocker amlodipine was more effective in reducing adverse cardiovascular outcomes than benazepril plus hydrochlorothiazide.20 BETA-ADRENERGIC BLOCKERS A beta blocker may be a good choice for treatment of hypertension in patients with another indication for a beta blocker, such as migraine headaches, some cardiac arrhythmias, angina pectoris, myocardial infarction, or heart failure, and possibly in younger patients (20/10 mm Hg above goal c often allows for lower doses of both drugs d all of the above Most studies that have shown outcome benefits of a diuretic in treating hypertension have used: a furosemide b metolazone c spironolactone d chlorthalidone A 70-year-old woman with a sulfonamide allergy asks you to recommend a diuretic as add-on therapy to lower her blood pressure Which of the following would be an appropriate choice for this patient? a hydrochlorothiazide b ethacrynic acid c bumetanide d furosemide Which of the following antihypertensive drugs can cause fetal and neonatal morbidity and death? a ACE inhibitors b ARBs c aliskiren d all of the above One advantage of ARBs over ACE inhibitors for treatment of hypertension is that they: a are significantly more effective b are safer for use during pregnancy c generally have fewer adverse effects d all of the above Which of the following calcium channel blockers usually causes an initial reflex tachycardia? a felodipine b nicardipine c nisoldipine d all of the above 10 Which of the following centrally acting alpha-adrenergic agonists is also used for treatment of hypertensive urgencies? a clonidine b guanfacine c methyldopa d all of the above 11 The triple drug combinations available in the US for treatment of hypertension all contain: a an ACE inhibitor b a thiazide-type diuretic c an ARB d a beta blocker 12 Which of the following drugs should generally be given with a beta blocker or a centrally-acting drug to minimize reflex tachycardia and a diuretic to avoid fluid retention? a clonidine b hydralazine c prazosin d aliskiren Which of the following antihypertensive drugs are less effective as initial monotherapy in black patients? a ACE inhibitors b calcium channel blockers c thiazide-type diuretics d all of the above ACPE UPN: 0379-0000-14-141-H01-P; Release: April 2014, Expire: April 2015 Treatment Guidelines from The Medical Letter • Vol 12 (Issue 141) • May 2014 ... • May 2014 37 Drugs for Hypertension 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 38 National Institute for Health and Clinical Excellence Hypertension: clinical management of primary hypertension. .. large, population-based cohort Hypertension 2014; 63:451 Drugs for chronic heart failure Treat Guidel Med Lett 2012; 10:69 Aliskiren (Tekturna) for hypertension Med Lett Drugs Ther 2007; 49:29 HH... et al 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the