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Therapeutics Tutoring
Sarah Darby September 14, 2017
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Acute Coronary Syndrome
Troponin assay Cardiac specific Rapid results Detectable levels = myocardial damage Rises in ~4 hours and remains elevated for several days Collect 2 samples 6 hours apart BNP Rise = increased ventricular wall stress ST segment ST elevation = injury T wave inversion = ischemia
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ST depression or T wave inversions
ACS UA NSTEMI STEMI Troponin Negative Positive EKG changes ST depression or T wave inversions ST elevation Artery Partial occlusion Complete occlusion
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ACS Catheterization Percutaneous coronary intervention (PCI)
Use of small catheter threaded through femoral artery to gauge health of heart May simply view heart’s status without “intervening” May perform PCI Percutaneous coronary intervention (PCI) May be called angioplasty With or without stent placement (usually with) Reperfusion Therapy Thrombolytic therapy (t-PA, reteplase, tenecteplase) PCI
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ACS Initial treatment Aspirin Nitrates Beta-blockers Anticoagulants
Other antiplatelet agents
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ACS Conservative management strategy Invasive strategy
AKA “Ischemia guided” Not going to the cath lab, not intervening Medication only Aspirin P2Y12 inhibitor Anticoagulant Invasive strategy Headed to the cath lab, intervening Possibly GPI in high risk patients Cath lab to determine need for PCI or CABG
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ACS
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ACS Unstable angina NSTEMI STEMI
While you are working in the ER, the physician asks for your recommendation concerning reperfusion therapy for a patient. What type of patients are eligible for reperfusion therapy? Unstable angina NSTEMI STEMI
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ACS Reduced rates of death, second MI, recurrent ischemia
Reperfusion therapy Either PCI or fibrinolytics Time = Muscle! Door to needle <30min Door to balloon <90min PCI > fibrinolysis Reduced rates of death, second MI, recurrent ischemia
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ACS Reperfusion therapy with fibrinolysis Tissue plasminogen activator
Reteplase Tenecteplase All given in combination with heparin. Major concern: intracranial bleeding T-PA has shortest duration When to use? ST elevation in at least 2 contiguous leads Patient presents within 12 hours of chest pain onset Successful reperfusion Prompt relief of chest pain Prompt resolution of ST elevation
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ACS Which agent acts by irreversible acetylation in order to inhibit platelet aggregation? Clopidogrel Aspirin LMWH Ticagrelor
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ACS JH arrives at ER at 11:00 am by way of EMS. Complains of CP and SOB onset 3 hours ago. JH states he took ASA 81mg just before calling What is your first course of action when he arrives? Initiate heparin continuous infusion Immediately send the pt to the cath lab Administer Aspirin 325mg chew and swallow Administer enoxaparin SQ
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ACS JH arrives at ER at 11:00 am by way of EMS. Complaints of CP and SOB onset 3 hours ago. JH states he took ASA 81mg just before calling 911. After JH is stabilized, the physician discusses with you the need for continual aspirin therapy at 162mg daily. How would you respond? Great idea! I agree with daily aspirin therapy, but let’s use 325mg daily for increased mortality benefit. I agree with daily aspirin therapy, but let’s use 81mg daily for reduced risk of bleeding and similar CV benefits. I disagree. Let’s use Warfarin 5mg daily.
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ACS In the acute management of ACS, what dose of Clopidogrel do you recommend? 600mg load, followed by 75mg daily 600mg load, followed by 150mg daily 300mg load, followed by 150mg daily 100mg load, followed by 75mg daily
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ACS Polymorphisms in which CYP enzyme may render Clopidogrel ineffective? CYP2B6 CYP1A2 CYP2C19 CYP3A4
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ACS JH is a 69 yo male with STEMI. He is started on DAPT with Aspirin and Clopidogrel. Due to his increased risk of bleeding, your team decides to add an agent for GI protection. What do you recommend? Omeprazole Pantoprazole Esomeprazole Ranitidine
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Which agent is not a prodrug?
ACS Which agent is not a prodrug? Clopidogrel Ticagrelor Prasugrel
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ACS Clopidogrel Prasugrel Ticagrelor
mg load, followed by 75mg daily Prodrug Slow onset Irreversible Affected by polymorphisms of CYP2C19 Prasugrel 60mg load, followed by 10mg daily PCI only! More efficient than Clopidogrel More bleeding than Clopidogrel CI: active bleed, history of TIA/stroke Not recommended: 75 years and older, weighing <60kg No polymorphism issues Ticagrelor 180mg load, followed by 90mg BID Not a prodrug Reversible Compliance important Avoid with 3A4 inhibitors
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ACS PCI w/stent Clopidogrel Prasugrel Ticagrelor Load 300-600mg 60mg
Maintenance 75mg daily 10mg daily 90mg BID Duration 1 year
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ACS PR is a 70 yo female who is now on the medicine floor s/p STEMI w/thrombolytic therapy. Her daughter states she helps her mom take her medications in the morning because she has trouble remembering by herself. What medications do you recommend before she is discharged? Aspirin 81mg indefinitely and Clopidogrel 75mg for 1 year Aspirin 81mg indefinitely and Prasugrel 10mg daily for 1 year Aspirin 81mg indefinitely and Ticagrelor 90mg BID for 1 year Aspirin 81mg and Clopidogrel 75mg for 6 months
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ACS Platelet glycoprotein IIb/IIIa inhibitors (GPIs)
Inhibits final common pathway in platelet aggregation Used for PCI w/stent Used with aspirin and heparin Highest evidence for high risk patients Positive troponin, previous MI, DM, LV dysfunction Studies were before thienopyridine agents available
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ACS Platelet glycoprotein IIb/IIIa inhibitors (GPIs) Abciximab
Monoclonal antibody Reversed with platelet transfusion Eptifibatide Peptide Dose adjust in poor renal function Tirofiban Non-peptide
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ACS BD is a 57 yo male with confirmed STEMI. The team decides to use pharmacological reperfusion. Which agent should not be used? Eptifibatide Enoxaparin Aspirin T-PA Metoprolol APhA Complete Review for Pharmacy
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ACS Anticoagulation Recommended for all patients regardless of treatment strategy. Unfractionated Heparin (UFH) Enoxaparin Bivalirudin
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ACS UFH 60 units/kg loading dose 12 units/kg/h IV
Goal: aPTT seconds Duration: 48 hours or until PCI is completed Also used with thrombolytic therapy Usually preferred for use during PCI Watch out for HIT
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ACS Enoxaparin Preferred in UA/NSTEMI 1mg/kg SQ every 12 hours
CrCl < 30ml/min should use 1mg/kg SQ every 24 hours STEMI w/ thrombolytic therapy IV bolus of 30mg, 1mg/kg SQ every 12 hours <75 yo Creatinine <2.5mg/dl in men Creatinine < 2.0mg/dl in women 0.75mg/kg every 12 hours, no IV bolus >75 yo If CrCl is ever <30ml/min, use 1mg/kg SQ every 24 hours. Watch out for HIT
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ACS Bivalirudin Used instead of heparin and GPI
Only for invasive strategy 0.75mg/kg loading dose, followed by 1.75mg/kg/h Initiate before PCI Used when patient has HIT
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ACS How long should a patient take a P2Y12 inhibitor after stent placement? 1 month 6 months 12 months 2 years
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ACS Which is true for a DES?
It releases antiproliferative agents that prevent new endothelium from forming around the stent DAPT therapy is crucial for at least 1 year The restenosis rate is lower than BMS All of the above
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ACS FD is a 45 yo male who runs marathons. He presents to the ED with CP after his morning run. PMH: angina, hyperlipidemia, HTN. Current meds: aspirin, rosuvastatin, nifedipine, and clonidine. His EKG shows acute ischemia. HR=52. BP=170/100. Which intervention is LEAST appropriate? Enoxaparin 1mg/kg SQ every 12 hours Metoprolol 50mg BID Nitroglycerin SL PRN Continuation of aspirin Morphine if NTG does not relieve pain APhA Complete Review for Pharmacy
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Post-MI (Sending patients home)
How can we reduce CV risk factors, prevent heart failure, prevent another MI or stroke, and prevent death? Modifiable: smoking cessation, weight loss, exercise, healthy diet, control of DM and HTN, and medication adherence Beta-blockers – reduce mortality, avoid ISA Aspirin 81 mg daily – prevent platelet aggregation Reduce mortality, avoid NSAIDs P2Y12 inhibitors – Clopidogrel, Prasugrel, Ticagrelor ACE inhibitors UA/NSTEMI: HF, EF<40%, HTN, DM STEMI: all patients If ARB needed: Candesartan or Valsartan
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Post-MI (Sending patients home)
Oddballs Eplerenone – LVEF <40% with HF/DM Not for renal dysfunction or hyperkalemia Nitrates All patients should receive Rx for sublingual NTG and counseling on appropriate use Lipid lowering therapy – statins CCB – no mortality or morbidity benefit post-MI
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ACS 59 yo female presents to ED with chest pain, SOB, n/v that started 2 hours ago. Her initial troponin is negative. What problem does she have? Stable angina Unstable angina NSTEMI STEMI I have no idea. Too early to tell
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ACS 59 yo female presents to ED with chest pain, SOB, n/v that started 10 hours ago. Her initial troponin is negative, and there are non-specific ST-T wave changes on her EKG. What problem does she have? Stable angina Unstable angina NSTEMI STEMI I have no idea. Too early to tell
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ACS 64 yo male presents to ED with crushing chest pain that started 5 hours ago. The EKG shows ST elevation and the troponin level is 0.06ng/ml. What problem is he having? Stable angina Unstable angina NSTEMI STEMI I have no idea. Too early to tell
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ACS 64 yo male (80kg) presents to ED with crushing chest pain that started 5 hours ago. The EKG shows ST elevation and the troponin level is 0.06ng/ml. What do you recommend? Aspirin 81mg Aspirin 325mg Metoprolol 100mg Clopidogrel 75mg
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ACS 64 yo male (80kg) presents to ED with crushing chest pain that started 5 hours ago. The EKG shows ST elevation and the troponin level is 0.06ng/ml. The healthcare team determines that Alteplase will be used for pharmacological reperfusion. What is the appropriate simultaneous therapy? 4,800 unit bolus UFH, followed by 960 units/h infusion 4,800 unit bolus UFH, followed by 1000 units/h infusion 4,000 unit bolus UFH, followed by 960 units/h infusion 4,000 unit bolus UFH, followed by 1000 units/h infusion
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ACS 67 yo male presents to ED with crushing chest pain that started 5 hours ago. The EKG shows ST elevation and the troponin level is 0.07ng/ml. PMH: DM, HTN, TIA. The healthcare team determines he will be going to the cath lab for PCI. Along with Aspirin, what treatment do you recommend? Prasugrel 60mg Clopidogrel 75mg Clopidogrel 600mg Ticagrelor 90mg
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ACS 63 yo female (60kg) presents to ED with chest pain that started 4 hours ago. The EKG shows no ST elevation but the troponin level is positive. PMH: HTN, DM, hyperlipidemia, HF, HIT. Her CrCl=55ml/min. The healthcare team decides to be proactive and take the Pt to the cath lab for PCI. Along with Aspirin 325mg and Prasugrel 60mg, what therapy is appropriate? Heparin 3600 unit bolus and Eptifibatide Bivalirudin 45mg loading dose, followed by 105mg/h Enoxaparin 30mg loading dose IV, followed by 60mg SQ daily Heparin 3600 unit bolus A is appropriate dosing and would be an option if she didn’t have a history of HIT C is the dosing for someone with a CrCl less than 30ml/min D might be appropriate (it’s the right dose) but she has hx of HIT and she would probably be considered high risk and could potentially use a GPI
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ACS BT is 65 yo female weighing 70kg who is post-ACS with DES placement and preserved LVEF. What is the best medication regimen for her? Aspirin 325mg daily, Clopidogrel 75mg daily, Diltiazem 240mg daily, Simvastatin 40mg daily Aspirin 81mg daily, Ticagrelor 90mg BID, Metoprolol tartrate 50mg BID, Atorvastatin 80mg daily Prasugrel 5mg daily, Metoprolol succinate 100mg daily, Simvastatin 40mg daily, Enalapril 10mg BID Aspirin 81mg daily, Prasugrel 10mg daily, Metoprolol tartrate 100mg BID, SL NTG Aspirin 325mg daily, Morphine 2-4mg IV PRN, oxygen, SL NTG APhA Complete Review for Pharmacy
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Therapeutics Tutoring Questions?
Sarah Darby September 14, 2017
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