ABCs of CVA Meds HyeJin Son, PharmD, BCPS. October 20, 2016

Transcription

1 ABCs of CVA Meds HyeJin Son, PharmD, BCPS October 20, 2016

2 Chisholm-Burns et.al. Pharmacotherapy: Principles and Practice 3 rd edition. 2013

3 Origin of Stroke Chisholm-Burns et.al. Pharmacotherapy: Principles and Practice 3 rd edition. 2013

4 Golden Hour of Stroke Time is brain Stroke scales Diagnostic studies Neuroimaging Glucose PT/INR BMP/CBC ECG/Cardiac biomarkers O 2 saturation Differential diagnosis Hypoglycemia Seizures Intoxication Complicated migraine CNS tumor CNS infection Jauch et al. Early Management of Acute Ischemic Stroke. Stroke. 2013;44:

5 Chisholm-Burns et.al. Pharmacotherapy: Principles and Practice 3 rd edition. 2013

6 Initial Care Acute Intervention Secondary Prevention Respiratory Support TPA Aspirin BP Lowering Antiplatelets Hemodynamic Support Interventional Radiology Anticoagulants for Afib Warfarin Novel Anticoagulants HMG-CoA-Reductase (Statins)

7 Blood Pressure in Acute Ischemic Stroke (AIS)

8 Blood Pressure in Acute Ischemic Stroke (AIS) Hypertension predominates AIS Goal BP dependent on intervention If TPA à BP < 180/105 for first 24 hours If no TPA à SBP < 220 or DBP < 120 Hypotension suggests alternative cause Arrhythmia Cardiac Ischemia Aortic dissection Shock/Sepsis Jauch et al. Early Management of Acute Ischemic Stroke. Stroke. 2013;44:

9 Jauch et al. Early Management of Acute Ischemic Stroke. Stroke. 2013;44: Acute Hypertension Treatment Drug Mechanism Dose (IV) Onset Duration Labetalol Alpha/Beta Blocker mg 2-8 mg/min infusion 2-5 min 2-6 hr Nicardipine Calcium Channel Blocker 5-15 mg/hr infusion 5-10 min 2-6 hr Hydralazine Arterial vasodilator 5-20 mg 10 min 1-4 hr Enalaprilat ACE-Inhibitor mg q6hr min hr Nitroprusside Arterial/venous vasodilator mcg/kg/min Seconds 1-2 min

10 Long-term Antihypertensive Therapy The most important intervention When Reasonable after the first 24 hours Whom Initiate for previously untreated patients Resume for previously treated patients Secondary prevention Goal: SBP <140 and DBP <90 Lifestyle modification Thiazide ± ACE Inhibitor Jauch et al. Early Management of Acute Ischemic Stroke. Stroke. 2013;44: Kernan et al. Stroke Prevention in Patients with Stroke and TIA. Stroke. 2014;45:

11 JAMA 2014;311(5):

12 Antiplatelets Aspirin 325 mg x1, then mg/day within hours Do not initiate aspirin within 24 hours of tpa Secondary Prevention of noncardioembolic stroke or TIA Aspirin mg once daily Clopidogrel 75 mg once daily Aspirin/ER dipyridamole 25 mg/200 mg twice daily Cilostazol 100 mg twice daily Kernan et al. Stroke Prevention in Patients with Stroke and TIA. Stroke 2014;45: Lansberg et al. Antithrombotic and thrombolytic therapy for ischemic stroke. Chest 2012;141:e601S-36S

13 Anticoagulants for Atrial Fibrillation (Afib) Use of CHA 2 DS 2 -VASc score 0: recommend no antithrombotic therapy 1: recommend antithrombotic therapy with oral anticoagulation or antiplatelet therapy but preferably oral anticoagulation 2: recommend oral anticoagulation with Warfarin Dabigatrin Rivaroxaban Apixaban Lane et al. Circulation. 2012;126: Kernan et al. Stroke Prevention in Patients with Stroke and TIA. Stroke 2014;45: January at el AHA/ACC/HRS Guideline for Atrial Fibrillation. J Am Coll Cardiol. 2014;64(21):

14 Anticoagulants Stroke Risk Assessment Tool CHADS2 CHA2DS2-VASc CHF 1 point Hypertension 1 point Age 75 year 1 point Diabetes 1 point Prior Stroke or TIA 2 points CHF 1 point Hypertension 1 point Age 75 year 1 point Diabetes 1 point Prior Stroke or TIA 2 points Vascular disease 1 point Age 65 year 1 points Sex category (female) 1 point Lane et al. Circulation. 2012;126:

15 Mechanism Compared to warfarin Warfarin (Coumadin) Vitamin K Antagonist Can use in patients with valvular afib Dabigatran (Pradaxa) Direct Thrombin Inhibitor Non-inferior Similar rates of hemorrhage but less ICH, more GIB. Increased MI Rivaroxaban (Xarelto) Direct Factor Xa Inhibitor Non-inferior Similar risk of major bleeding but lower ICH and fatal bleeding, more GIB Apixaban (Eliquis) Direct Factor Xa Inhibitor Superior Less risk of bleeding and mortality Edoxaban (Savaysa) Direct Factor Xa Inhibitor Non-inferior Lower rates of bleeding Trial SPAF RE-LY ROCKET AF ARISTOTLE Engage AF-TIMI 48 Dose for Afib Various doses daily 150 mg twice daily 20 mg daily with evening meal 5 mg twice daily 60 mg daily Renal adjustment No CrCl 30-49: If concomitant dronedarone or ketoconazole 75 mg twice daily CrCl 15-30: 75 mg twice daily or avoid CrCl <15: Avoid use CrCl ml/min: 15 mg daily CrCl <15 ml/min: Do not use Decrease dose to 2.5 mg twice daily if 2 of the following: 80 years old; Weight 60 kg; SCr 1.5 Do not use if CrCl is >95 ml/min CrCl ml/min: 30 mg daily CrCl <15 ml/min: Do not use Reversal agent Vitamin K Idarucizumab (Praxbind) In development: Andexanet alfa (PRT064445) Phase III trials Aripazine (PER977) Phase II trials Hanley el al. J Thorac Dis Feb; 7(2): , Stacy et al. Cardiol Ther 2016 June;5(1):1-8

16 Relative risk reductions of various outcomes in patients with nonvalvular atrial fibrillation receiving various antithrombotic regimens as compared with warfarin or its derivatives Acenocoum = acenocoumarol ASA = acetylsalicylic acid CI = confidence interval Antonio Culebras et al. Neurology 2014;82:

17 Hemorrhagic Stroke Pearls No pharmacotherapy to directly treat bleeding Pharmacotherapy is aimed at supportive care Anticoagulation reversal FFP, PCC, etc Blood pressure/cerebral perfusion pressure Cerebral edema/intracranial pressure Vasospasm management (Aneurysmal SAH) Jauch et al. Early Management of Acute Ischemic Stroke. Stroke. 2013;44: Kernan et al. Stroke Prevention in Patients with Stroke and TIA. Stroke. 2014;45:

18 Hemorrhagic Stroke Blood Pressure SBP < 160 MAP < 110 CPP = MAP ICP CPP > 60 Short acting medications Antihypertensives Vasopressors Prevent hematoma expansion Maintain cerebral perfusion Jauch et al. Early Management of Acute Ischemic Stroke. Stroke. 2013;44: Kernan et al. Stroke Prevention in Patients with Stroke and TIA. Stroke. 2014;45:

19 Cholesterol Management Continue statin during the acute period Secondary prophylaxis Statin therapy with intensive lipid-lowering effects (SPARCL study) Manage according to 2013 ACC/AHA cholesterol guidelines ASCVD = atherosclerotic cardiovascular disease ACC = American College of Cardiology AHA = American Heart Association Jauch et al. Early Management of Acute Ischemic Stroke. Stroke. 2013;44: Kernan et al. Stroke Prevention in Patients with Stroke and TIA. Stroke. 2014;45:

20 Four Statin Benefit Groups Individuals: 1. Clinical ASCVD 2. Primary elevations of LDL-C > 190 mg/dl 3. Diabetes aged 40 to 75 yrs with LDL-C mg/dl and without clinical ASCVD 4. Without clinical ASCVD or diabetes with LDL-C mg/dl and estimated 10-yr ASCVD risk > 7.5% Stone et al. Circulation 2013;00:

21 Stone et al. Circulation 2013;00:

22 Stone et al. Circulation 2013;00:

23 Statins Efficacy LDL-C reduction 25-62% Rule of 6 = Each doubling of daily dose produces an additional 6% average reduction Moderately effective at lowering triglycerides Modestly raise HDL-C Chisholm-Burns et.al. Pharmacotherapy: Principles and Practice 3 rd edition. 2013

24 Statins Adverse Effects Constipation Abdominal pain Diarrhea Dyspepsia Nausea LFT increase (< 2%) Myopathy, including rhabdomyolysis (0- <0.5%) Stone et al. Circulation 2013;00:

25 Post-Stroke Seizures Post stroke seizure: <10% Recurrence: rare to ~6% Early vs. late onset Predictors: hemorrhagic transformation (HT), severity and cortical location No primary prophylaxis Secondary prophylaxis if multiple early seizures or ICH or HT Short term/monotherapy with antiepileptic agent Jauch et al. Early Management of Acute Ischemic Stroke. Stroke. 2013;44: Beleza et al. Neurologist May; 18(3):

26 Post-Stroke Seizures Recurrent seizures after stroke should be treated in a manner similar to other acute neurological conditions, and antiepileptic agents should be selected by specific patient characteristics. Jauch et al. Early Management of Acute Ischemic Stroke. Stroke. 2013;44:

27 Seizure Types Focal (Partial) Seizure Simple Complex Secondarily generalized Generalized Absence (petit mal) Myoclonic Clonic Tonic-clonic (grand mal) Atonic Status Epilepticus: prolonged seizure after 5 minutes Jauch et al. Early Management of Acute Ischemic Stroke. Stroke. 2013;44:

28 Status Epilepticus Treatment First-line therapy (Benzodiazepine therapy preferred) Lorazepam 0.1 mg/kg intravenously (max 4 mg/dose) Midazolam 5 10 mg intramuscularly Second-line therapy Valproate mg/kg intravenously (Fos)Phenytoin mg/kg intravenously Phenobarbital 20 mg/kg intravenously Levetiracetam 1 3 g intravenously Neurocrit Care 2012;17:3-23

29 Chisholm-Burns et.al. Pharmacotherapy: Principles and Practice 3 rd edition. 2013

30 Phenytoin (Dilantin) Carbamazepine (Tegretol) Levetiracetam (Keppra) Zonisamide (Zonegran) Gabapentin (Neurontin) Lamotrigine (Lamictal) Mechanism Fast Na channel blocker Fast Na channel blocker Unknown Loading Dose 10-20mg/kg None Not routine ( mg) Maintenance Dose Therapeutic Range 4-7mg/kg/day Total: mcg/ ml Free: 1-2 mcg/ml mg/kg/day divided TID-QID BID if XR mg/ day Na and Ca channel stabilization Ca channel stabilization, increase GABA None N/A None mg/day 900-3,600mg/day tid-qid 4-12mcg/ml N/A N/A N/A N/A Fast Na channel blocker mg/day divided BID-TID Centration Dependent Adverse Effects Ataxia, diplopia, sedation, nystagmus Diplopia, nausea, dizziness Sedation, anxiety, irritability Dizziness, sedation Sedation Diplopia, dizziness, headaches Idiosyncratic Adverse Effects Anemia, gingival hyperplasia, hirsutism, rash Leukopenia, rash, hyponatremia Kidney stones, metabolic acidosis, weight loss Peripheral edema, weigh gain Rash. May progress to Stevens-Johnson Reaction Notes Highly protein bound. Maximal infusion rate of 50 mg/minute. Non-linear. Autoinduction. Genetic variability No DDI with other seizure medications. Renal dose adjustment Renal dose adjustment necessary Start low and titrate slowly due to risk of rash. Valproic acid decreases metabolism (lower) Zelano. Ther adv neurol disor Sep; 9(5):

31 Thank you!