Pharmacotherapy stroke

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    Pharmacotherapy in patient with stroke

    (ischemic stroke) (hemorrhage stroke) thrombolytic agent

    1. stroke 2.

    stroke 3. stroke 4.

    stroke

    1. 2. 3.

    1. 2. 3.

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    Pharmacotherapy in patient with stroke

    (stroke) (neurologic deficit) ..2542 15 9 thrombolytic drug t-PA 3 antiplatelets aspirin (Epidemiology) 3 5 150,000 (Etiology and classification) (neurological deficit) 24 2 ischemic hemorrhagic stroke ischemic 88 1

    Hemorrhagic stroke 3 1. Subarachnoid hemorrhage subarachnoid space

    aneurysm 2. Intracerebral hemorrhage

    ventricle subarachnoid

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    3. Subdural hematomas dura arachnoid

    (arterosclerosis)

    Ischemic stroke (thrombus) (cardiogenic embolism) AF emboli 5

    1. Atheriotic cerebrovascular disease atherosclerotic plaque fibrin, cholesterol, platelet, macrophage, foam cell, smooth muscle cell calcium

    2. Lacuna stroke Penetrating artery disease perforating branches stroke

    3. Cardiogenic embolism emboli emboli cardiogenic embolism

    4. Cryptogenic stroke stroke 5. Stroke

    Hemodynamic stroke low flow state cerebral blood flow

    Vascular disease dissection, Moya-Moya disease (MMD circle of willis), Vasculitis

    Venous sinus thrombosis

    Abnormal coagulation protein C/S hyperviscosity syndrome

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    1 Stroke (Fagan et al, 2008) (Clinical classification)

    1. Transient ischemic attack (TIA) 24 ischemic stroke

    2. Reversible ischemic neurological deficit (RIND) 24 3

    3. Progressive Stroke 4. Complete Stroke progressive complete

    irreversible (pathogenesis) 1. Atheroma 2. Hypertensive vascular disease 3. Embolism of healthy arteries 4. arteritis

    (Pathophysiology)

    15 ( 2 ) phosphorylation ATP

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    ischemic stroke origin internal carotid artery, carotid siphon middle cerebral artery, basilar artery intracranial part vertebral artery plaque

    hemorrhagic stroke

    Congenital and acquired cerebrovascular disease

    Aneurysms

    Arteriovenous malformations

    anticoagulant warfarin VTE ischemic stroke

    amphetamine

    Angiostrongylus

    1 stroke (Fagan et al, 2008)

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    (Risk factors) CHF left ventricular hypertrophy 2 1

    1 stroke

    Nonmodifiable risk factors or risk markers

    Age Gender Race Family history of stroke Low birth weight

    Modifiable, well-documented Hypertensionsingle most important risk factor for ischemic stroke Atrial fibrillationmost important and treatable cardiac cause of stroke Other cardiac diseases Diabetesindependent risk factor Dyslipidemia Cigarette smoking Alcohol Sickle cell disease Asymptomatic carotid stenosis Postmenopausal hormone therapy Lifestyle factorsassociated with stroke risk

    Obesity

    Physical inactivity

    Diet Potentially modifiable, less-well documented

    Oral contraceptives Migraine

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    Drug and alcohol abuse Hemostatic and inflammatory factorsfibrinogen linked to increased risk Homocysteine Sleep disordered breathing

    (Clinical presentation)

    Ischemic stroke 1. (location of ischemia)

    2. (area of ischemia)

    3. (severity of ischemia)

    embolism thrombus

    4. collateral (collateral circulation) collateral

    Ischemic stroke 1. Atheriotic stroke

    2. Lacunes stroke Pure mortor hemiplegia Pure hemisensory syndrome thalamus Ataxic-hemiparesis

    3. Cardiogenic embolism -

    Hemorrhagic stroke

    1. 2. 50

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    3. Glasgow Coma Scale 2

    4. (meningism) ventricle arachnoid space

    5. (apnea) posterior fossa

    6. (Diagnosis)

    1. 2.

    cardiovascular system

    3. CT-scan ischemic

    hemorrhagic stroke MRI (magnetic resonance imaging)

    MRI CT-scan

    Carotid duplex ultrasound ischemic stroke sensitivity specificity

    Transcranial Doppler ultrasound circle of Willis

    Cerebral angiogram

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    2 Glasgow Coma Scale (Central nervous system, 2012)

    1. 2.

    Ischemic stroke (Primary agents) 24

    1. (Acute resuscitation)

    Ischemic stroke

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    1.1 ABC oxygen oxygen

    1.2 stroke acute stroke autoregulation 80 10 4-6 acute stroke cerebral retrograde 220/120 mmHg AHA/ASA ACEIs diuretics (hemorrhagic transformation ischemic stroke 220/120 mmHg target organ damage hypertensive encephalopathy, aortic dissection, acute renal failure, acute pulmonary edema acute myocardial infarction labetalol, nicardipine sodium nitroprusside 15 24

    3 acute ischemic stroke ( .)

    thrombolytic therapy

    Systolic BP 220 diastolic 120

    - aortic dissection, acute myocardial infarction, pulmonary edema, hypertensive encephalopathy)

    - stroke - stroke ( hypoxia, increased

    intracranial pressure, seizure, hypoglycemia)

    Systolic BP 220 diastolic 121-140

    - Labetalol 10-20 .IV 1-2 2 10 300 .

    - Nicardipine IV infusion 5 ./ 2.5 ./ 15 15 ./

    - 10 15 Diastolic > 140 Nitroprusside 0.5 // IV infusion

    10 15

    thrombolytic therapy thrombolytic therapy

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    Systolic BP > 185 diastolic > 110 Labetalol 10-20 .IV 1-2 1 nitropaste 1-2

    thrombolytic therapy 1. Monitor blood pressure - 15 2 30 6

    16 2. Diastolic BP > 140 Sodium nitroprusside 0.5 mcg/kg/ IV infusion

    3. Systolic BP > 230 diastolic 121-140

    - Labetalol 10 IV 1-2 2 10 300 2-8 ./ - Nicardipine 5 ./ IV infusion 2.5 / 5 15 ./ sodium nitroprusside

    4. Systolic BP180-230 diastolic 105-120

    Labetalol 10 IV 1-2 2 10-20 300 . IV dose 2-8 ./

    ACCESS trial

    ARBs candesartan ischemic stroke 190/100 mmHg 1 7 candesartan 30 1 30 1 candesartan 24 ischemic stroke

    1.3 central line SwanGanz catheter dextrose 120 insulin

    1.4 hyperthermia 2-3 37 paracetamol

    2. (Reperfusion)

    ischemic stroke thromboemboli thrombolytic

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    thrombolytic stroke UFH, LMWHs

    (Thrombolytic drugs) streptokinase, urokinase , anistreplase tissue plasminogen

    activator (t-PA) plasminogen plasmin fibrin plasmin antiplasmin thrombolytic plasmin fibrin antiplasmin

    thrombolytic drug thrombus selective cereboli angiogram thrombitic drug rt-PA 0.9 IV bolus 10 90 IV infusion 60 3 90 Jena (2010) thrombolytics 4.5 90

    thrombolytic drug 1. acute ischemic stroke 2. 3 ( 2

    3. CT scan

    Thrombolytic drugs 1. bacterial endocarditis 2. 3 3. 3 4. hemorrhagic stroke 5. (major surgery) 14 (minor surgery)

    10 (lumbar puncture) 6. 7. 21 8. hemodialysis 9. PTT > 40 , INR > 1.5

    (platelet count) < 100,000 / 10. SBP > 185 , DBP > 110

    11. 12. < 50 > 400

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    (Anticoagulant) UFH LMWHs

    heparin Loading dose 50-70 continuous IV infusion 10-25 // aPTT 1.5-2.0

    (Antiplatelet drug) ischemic stroke

    5-20 2-3 ischemic stroke

    Aspirin ischemic stroke 25 160-300 mg/day Neuroprotective agents CCBs calcium protease phospholipase free radical leukotriene calcium calcium nimodipine voltage-dependent calcium channel type L nimodipine 120 18 48 hypotension NMDA antagonist excitatory neurotransmitter calcium receptor channel CCB calcium nitric oxide related neurotoxicity neuron Free radical scavengers cerebral blood flow ischemic cerebral edema tirilazad superoxide dismutase metabolism (decreasing cerebral metabolic demands) blood flow metabolism metabolism barbiturate

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    Barbiturates metabolism (secondary treatment) acute Warfarin ischemic stroke cardioembolism INR 2-3 ASA warfarin recurrent ischemic stroke cardioembolism warfarin aspirin recurrent ischemic stroke WASID warfarin (INR 2-3) aspirin ischemic stroke/TIA intracranial artery 50 warfarin aspirin warfarin aspirin stroke intracranial stenosis warfarin noncardioembolism cardioembolism ischemic stroke ( 20 ischemic stroke ) ischemic stroke atrial fibrillation (AF), acute myocardial infraction, valvular heart disease prosthetic heart valve warfarin INR 2-3 EAFT warfarin aspirin cardioembolic stroke warfarin aspirin AF (bleeding) AHA/ASA warfarin ischemic stroke/TIA 2 warfarin 2 warfarin aspirin 325 rheumatic mitral valve disease AF warfarin target INR 2.5 (2.0-3.0) recurrent embolism aspirin 80 mg aortic valve disease AF recurrent stroke/TIA AF warfarin Antiplatelets

    1. Aspirin stroke vascular event ischemic stroke 50-325 mg

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    ischemic stroke/TIA aspirin 4

    4 major bleeding rate aspirin

    aspirin (mg/day) Rate of major bleeding 100 < 1.5 % 100-200 1.56 %

    200 5.0 % aspirin clopidigrel clopidogrel aspirin esomeprazole 40 aspirin 320 1 clopidogrel aspirin esomeprazole ( 7.9; 95%CI : 3.4-12.4 ; p=0.001)