Updates in Therapeutics: 2013 Pharmacotherapy Preparatory Review and Recertification Course
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1 AMERICAN COLLEGE OF CLINICAL PHARMACY Updates in Therapeutics: 2013 Pharmacotherapy Preparatory Review and Recertification Course POSTTEST ANSWERS SESSION 8 Cardiology I 1. Answer B: NTG intravenously 5 mcg/minute. In hypertensive emergencies, it is important to lower the mean arterial pressure by no more than 20% 25% during the first hour. The preferred agents to accomplish this goal are intravenous, easily titratable, and quick in onset. There is no one preferred agent, yet because this man presents with an acute coronary syndrome (ACS), agents such as intravenous NTG are preferred (Answer B). Although β-blockers could be used to lower BP and offer advantages in ACS, esmolol (Answer C) is not the best choice in this case given the patient s HR of 60 beats/minute. Sodium nitroprusside (Answer A), which causes a coronary steal effect, is not the best agent of choice in ACS because it can worsen myocardial oxygen supply in this acute setting. Hydralazine, which can induce reflex tachycardia and increase myocardial oxygen consumption, is not the best choice in this ACS setting. 1. Saseen JJ, MacLaughlin EJ. Chapter 19. Hypertension. In: Pharmacotherapy: A Pathophysiologic Approach, 8th ed. New York: McGraw-Hill, 2011: Marik PE, Varon J. Hypertensive crises: challenges and management. Chest 2007;131: Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension 2003;42: Answer D: Bivalirudin 0.75-mg/kg IVB x 2 and a 1.75-mg/kg/hour infusion plus clopidogrel 600-mg oral loading dose. This patient is experiencing an ACS, specifically a non ST-segment elevation myocardial infarction (NSTEMI), and an invasive strategy is chosen. The anticoagulation strategy treatment for ACS generally includes one anticoagulant (UFH, low-molecular-weight heparin [LMWH], fondaparinux, or bivalirudin) and up to three different classes of antiplatelet medications (aspirin and a P2Y12 receptor antagonist, with or without a glycoprotein inhibitor), depending on several factors. Answer A is not the best choice because the dose of enoxaparin in NSTEMI is 1 mg/kg subcutaneously; the additional bolus of 30 mg intravenously is reserved for a patient with a totally occlusive thrombus, as in STEMI. Answer B is not the best choice because using more than one anticoagulant is not appropriate. Furthermore, fondaparinux would not be the best choice, given that an invasive strategy was chosen for this man. Fondaparinux was given a class III, or harmful, recommendation according to the 2011 PCI guidelines because of catheter-related thrombosis. Thrombolytic therapy has no role in the treatment of unstable angina (UA)/NSTEMI and is not the best choice for this patient, who is headed to the cardiac catheterization laboratory. The most appropriate option is Answer D, which includes bivalirudin, a direct thrombin inhibitor as anticoagulant strategy, and appropriate loading doses of antiplatelet combination, aspirin, and clopidogrel. 1. Jneid H, Anderson JL, Wright RS, et al ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-st-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2012;126: Cardiology I and II Posttest Answers 1
2 2. Levine GN, Bates ER, Blankenship JC, et al ACCF/AHA/SCAI guideline for percutaneous coronary intervention: executive summary. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation 2011;124: Answer C: Aspirin 81 mg indefinitely plus clopidogrel 75 mg daily for 12 months. The choice of which P2Y12 receptor antagonist in the ACS setting depends on patient presentation and contraindications, as well as on whether PCI is involved. The 2012 UA/NSTEMI focused update gives a class I recommendation for clopidogrel, ticagrelor, and prasugrel in the ACS setting in patients undergoing PCI. This patient had a TIA in the past, which is a contraindication to prasugrel use. Therefore, Answer A and Answer D are not appropriate for this patient. Although the loading dose of aspirin is generally mg in the acute setting, current guidelines state that it is reasonable to use lower doses of aspirin (i.e., 81 mg) in preference to higher doses (i.e., 325 mg) at the time of discharge. Furthermore, ticagrelor (Answer B) has a black box warning regarding reduced effectiveness when doses higher than 100 mg daily are used with it concomitantly. Finally, after drugeluting stent placement in an ACS setting, the time recommended for dual antiplatelet therapy is a minimum of 12 months. 1. Jneid H, Anderson JL, Wright RS, et al ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-st-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2012;126: Levine GN, Bates ER, Blankenship JC, et al ACCF/AHA/SCAI guideline for percutaneous coronary intervention: executive summary. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation 2011;124: Answer A: Adenosine 6 mg intravenously. Vagal maneuvers and adenosine are the preferred initial therapy to terminate stable paroxysmal supraventricular tachycardia (PSVT). At this point, because vagal maneuvers were not successful, adenosine at a dose of 6 mg as a rapid intravenous push can be given. Adenosine should be administered through a large vein and followed immediately by a 20-mL saline flush. If the rhythm does not convert within 1 2 minutes, a second and third dose of 12 mg as described earlier may be tried. Amiodarone (Answer B) is useful in the treatment of stable wide complex tachycardia (not narrow) and is not the best choice in this case. Neither epinephrine (Answer C) nor atropine (Answer D) would slow the HR, and neither is appropriate for this patient with PSVT. Neumar RW, Otto CW, Link MS, et al. Part 8: adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010:122(suppl 3):S729-S Answer A: Discontinue metolazone and furosemide. Diuresis is important in the treatment of ADHF. However, overly aggressive diuresis should be monitored for carefully. The patient is currently showing signs of overdiuresis, which include a BUN/SCr bump beyond baseline, and greater than a 20:1 ratio indicates a dry state. Together with orthostatic symptoms, it should lead the clinician to consider holding diuretic therapy (Answer A). If the patient had continued signs and symptoms after diuresis was discontinued, an inotrope could be considered; however, epinephrine (Answer B) is not an inotrope of choice. The patient has a Cardiology I and II Posttest Answers 2
3 contraindication to spironolactone at present (SCr is greater than 2.5); therefore, spironolactone is not preferred at this time. Milrinone (Answer D) could be considered if the patient required inotropic therapy after the overdiuresis was corrected. 1. Hunt SA, Abraham WT, Chin MH, et al focused update incorporated into the ACC/AHA 2005 guidelines for the diagnosis and management of heart failure in adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in collaboration with the International Society for Heart and Lund Transplantation. J Am Coll Cardiol 2009;53: Weintraub NL, Collins SP, Pang PS, et al. Acute heart failure syndromes: emergency department presentation, treatment, and disposition: current approaches and future aims: a scientific statement from the American Heart Association. Circulation 2010;122: Lindenfield J, Albert NM, Boehmer JP, et al. HFSA 2010 comprehensive heart failure practice guideline. J Card Fail 2010;16:e1-e156. Cardiology II 6. Answer B: Warfarin with a goal international normalized ratio (INR) of 2 3. This patient has hypertension and diabetes, which would give her a CHADS2 score of 2; therefore, she is considered an intermediate stroke risk. The guidelines of the American College of Chest Physicians (ACCP) recommend anticoagulation over aspirin therapy in patients with a CHADS2 score of 1 or higher. Therefore, the choice of aspirin alone (Answer A) would be incorrect. This patient s estimated creatinine clearance (CrCl) is around 44 ml/minute. From this, if dabigatran were chosen over warfarin as an anticoagulant, the correct dose of dabigatran would be 150 mg twice daily. A dabigatran dose of 75 mg twice daily (Answer D) would be indicated if her CrCl were below 30 ml/minute or if she were taking a P-glycoprotein inhibitor such as dronedarone or ketoconazole. The dose of rivaroxaban that would be appropriate for this patient given her degree of renal dysfunction would be 15 mg/day, not 20 mg/day (Answer C). 1. You JJ, Singer DE, Howard PA, et al. Antithrombotic therapy for atrial fibrillation. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed. American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141(suppl):e513S-e575S. 2. Dabigatran (Pradaxa) [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, May Rivaroxaban (Xarelto) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, December Answer A: Atorvastatin 40 mg orally at bedtime. For B.D. to attain his initial LDL-C goal of less than 100 mg/dl, he will need to achieve at least a 36% reduction in his LDL-C. Atorvastatin at a dose of 40 mg/day (Answer A) will result in about a 50% reduction in LDL-C. Because this patient is taking diltiazem as well as amlodipine, the doses of simvastatin and lovastatin would not be appropriate. The maximal daily dose of lovastatin in combination with diltiazem is 20 mg (Answer C). The maximal daily dose in combination with amlodipine is 20 mg (Answer B). The maximal dose of simvastatin in combination with diltiazem is 10 mg (Answer B). Answer D is incorrect because fluvastatin would only provide a 25% reduction, falling short of the 36% needed for his initial LDL-C goal of less than 100 mg/dl. 1. Grundy SM, Cleeman JI, Bairey N, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004;110: Simvastatin [prescribing labeling]. Whitehouse Station, NJ: Merck & Co., June Cardiology I and II Posttest Answers 3
4 3. Lovastatin [prescribing information]. Whitehouse Station, NJ: Merck & Co., February Answer A: Initiate eplerenone 25 mg/day. Even though L.G. has no signs or symptoms of HF, she has diabetes and a reduced LVEF (less than 40%). According to the results of the EPHESUS trial, adding eplerenone to optimal medical therapy reduced morbidity and mortality in this patient population (Answer A). Adding eplerenone would provide additional benefit by helping her achieve her goal BP of less than 130/80 mm Hg. Increasing lisinopril from 40 mg/day to 80 mg/day would minimally affect the lowering of her BP (Answer B). Although amlodipine has shown a neutral effect in patients with HF (the PRAISE II trial), this patient is currently without any signs or symptoms; thus, given her recent myocardial infarction (MI) and diabetes, eplerenone would be the optimal choice. Her β-blocker therapy is already optimized, and her HR is already low; therefore, it would be inappropriate to increase her dose of metoprolol (Answer D). 1. Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. For the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators. N Engl J Med 2001;348: Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7). National Heart, Lung, and Blood Institute. Hypertension 2003;42: Antman EM, Hand M, Armstrong PW, et al focused update of the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction. Circulation 2008;117: Answer C: 4 weeks. The ACCP guidelines recommend at least 4 weeks of anticoagulation after cardioversion, even if the duration of the AF is less than 48 hours (Answer C). Answer A, Answer B, and Answer D are incorrect because these durations are inappropriate after cardioversion. If the patient had been in AF for greater than 48 hours, he would need to be fully anticoagulated for at least 3 weeks before cardioversion. Reference: You JJ, Singer DE, Howard PA, et al. Antithrombotic Therapy for Atrial Fibrillation. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed. American College of Chest Physicians Evidence- Based Clinical Practice Guidelines. Chest 2012;141(suppl):e513S-e575S. 10. Answer D: Initiate atorvastatin 40 mg/day to achieve an initial LDL-C goal of less than 100 mg/dl. His calculated Framingham Risk Score would result in a risk score of 13%, which would warrant an initial LDL-C goal of less than 130 mg/dl. However, diabetes is not included in the Framingham Risk Score because it is considered a coronary heart disease (CHD) risk equivalent; therefore, having the same 10-year risk as individuals with prior CHD, he would be considered high risk, and his 10- year risk would then be greater than 20%. Therefore, his initial LDL-C goal should be less than 100 mg/dl (Answer D). Answer A and Answer C are not appropriate because initiating a fibrate to treat elevated TG is only indicated when TG are above 500 mg/dl. His TG concentration is only 333 mg/dl and does not warrant pharmacologic treatment at this time. In addition, using gemfibrozil in combination with simvastatin or atorvastatin increases the risk of rhabdomyolysis. With simvastatin, the use of gemfibrozil is contraindicated. Caution should be exercised when using gemfibrozil with atorvastatin. An LDL-C goal of less than 130 mg/dl would not be appropriate, given this patient s recent diagnosis of diabetes, smoking history, and other risk factors (Answer B). Cardiology I and II Posttest Answers 4
5 1. Grundy SM, Cleeman JI, Bairey N, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III. Guidelines. Circulation 2004;110: Simvastatin [prescribing labeling]. Whitehouse, NJ: Merck & Co., June Cardiology I and II Posttest Answers 5
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