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Pharmacotherapy of Stroke
- 1. Pharmacotherapy of Stroke (Cerebrovasculardisorder) 9/23/2021 1 Pharmacotherapy of Stroke By Tolcha.R
- 2. Outline • Definition • Riskfactors • Pathophysiology • Clinical presentations • Diagnosis • Desired outcome • Treatment • Evaluation of Therapeutic outcomes 9/23/2021 2 Pharmacotherapy of Stroke By Tolcha.R
- 3. Definition • Stroke isa term used to describe – an abrupt onset of focal neurologic deficit that lasts at least 24 hours and is presumed to be of vascular origin • Stroke can be either ischemic or hemorrhagic • Transient ischemic attacks (TIAs) are – focal ischemic neurologic deficits lasting less than 24 hours and usually less than 30 minutes – TIA fuently result from small clots breaking away from larger, distant blood clots. – These emboli are then dissolved by the fibrinolytic system, allowing re-establishment of blood flow and return of neurologic function. 9/23/2021 3 Pharmacotherapy of Stroke By Tolcha.R
- 4. Risk Factors ForStroke • Non-modifiable risk factors – increased age – male gender – race (African American, Asian, Hispanic) – family history of stroke – low birth weight • Major modifiable risk factors – hypertension – cardiac disease (especially atrial fibrillation) – diabetes mellitus – dyslipidemia – cigarette smoking – obesity, and physical inactivity. – Postmenopausal hormone therapy (women 50-74 years old) 9/23/2021 4 Pharmacotherapy of Stroke By Tolcha.R
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- 7. Classification of Ischemicstroke 9/23/2021 Pharmacotherapy of Stroke By Tolcha.R 7
- 8. Non-lacunar Ischemic stroke 9/23/2021Pharmacotherapy of Stroke By Tolcha.R 8
- 9. Cryptogenic(unknown cause) 9/23/2021 Pharmacotherapyof Stroke By Tolcha.R 9
- 10. Ischemic Stroke • Ischemicand hemorrhagic events have similar symptoms and must be distinguished before initiating treatment • strokes account for 88% of all strokes and are due either to – local atherosclerosis of cerebral blood vessels – Embolus to cerebral arteries from a distant clot. Cerebral atherosclerosis is a causative factor in most cases of ischemic stroke, although 30% are of unknown etiology. • Emboli can arise either from intra- or extracranial arteries. – 20% of embolic strokes arise from the heart. 9/23/2021 10 Pharmacotherapy of Stroke By Tolcha.R
- 11. Ischemic Stroke Cerebralinfarctions can present in three forms: Stable Condition in which the neurologic deficit is permanent, will not improve, and will not deteriorate. Improving marked by return of previously lost neurologic function over the course of several days or weeks. progressing. the patient's neurologic status continues to deteriorate after the initial onset of focal deficits 9/23/2021 Pharmacotherapy of Stroke By Tolcha.R 11
- 12. Pathophysiology • Both embolicand thrombotic, affecting the cerebral vasculature are typically arterial in origin and are formed primarily by fibrin. • Tissue injury or turbulent blood flow causes the release of adenosine diphosphate (ADP), thrombin, epinephrine, and a variety of other substances to stimulate platelet migration. • Exposure of collagen and other subendothelial surfaces of the blood vessel wall causes adhesion of platelets to the damaged vessel wall. • As platelets adhere and aggregate, phospholipase is activated, leading to the splitting of arachidonic acid from platelet membrane phospholipids. 9/23/2021 Pharmacotherapy of Stroke By Tolcha.R 12
- 13. Pathophysiology • This beginsa cascade of events ultimately ending in the formation of thromboxane Az (TXAz) and prostacyclin. • Prostacyclin inhibits platelet aggregation and is a powerful vasodilator, whereas TXAz is a potent inducer of platelet release and aggregation. • Prostacyclin is formed in and released from arterial and venous walls. • TXAz is formed in and released from platelets. • The delicate balance between the actions of these two compounds controls thrombogenesis. • When a clot is formed, it can either embolize to the cerebral vasculature or occlude a cerebral artery. 9/23/2021 Pharmacotherapy of Stroke By Tolcha.R 13
- 14. Pathophysiology… • Cerebral bloodflow in the normal adult brain is 30 to 70 mL 100 g/minute. • When cerebral blood flow is less than 20 mU100 g/minute, various compensatory mechanisms are activated. • These include vasodilation and increased oxygen extraction. • If the artery is further occluded and cerebral blood flow is reduced to less than 12 mU100 g/minute, the affected neurons become sufficiently anoxic to die within minutes • Rapid re-establishment of blood flow to the ischemic area can delay, prevent, or limit the onset of infarction, improving the outcome of the acute stroke. 9/23/2021 Pharmacotherapy of Stroke By Tolcha.R 14
- 15. Hemorrhagic Stroke • Theprimary causes of a cerebral hemorrhage include: Cerebral artery aneurysm Arteriovenous malformation, Hypertensive hemorrhage, and trauma. • Hemorrhagic strokes account for 12% of strokes and include – Subarachnoid hemorrhage • may result from trauma or rupture of an intracranial aneurysm or arteriovenous malformation. – Intracerebral hemorrhage • occurs when a ruptured blood vessel within the brain parenchyma causes formation of a hematoma. – Subdural hematomas • most often caused by trauma 9/23/2021 15 Pharmacotherapy of Stroke By Tolcha.R
- 16. Cont… • The presenceof blood in the brain parenchyma causes damage to surrounding tissue through – a mass effect and the neurotoxicity of blood components and their degradation products. • Compression of tissue surrounding hematomas may lead to secondary ischemia. • Much of the early mortality of hemorrhagic stroke is due to an abrupt increase in intracranial pressure that can lead to herniation and death. 9/23/2021 16 Pharmacotherapy of Stroke By Tolcha.R
- 17. Clinical Presentations • Thepatient may not be able to give a reliable history because of cognitive or language deficits – Information may need to be obtained from family members or other witnesses • The patient may experience – weakness on one side of the body – inability to speak – loss of vision – Vertigo – falling • Ischemic stroke is not usually painful, but headache may occur and may be severe in hemorrhagic stroke 9/23/2021 17 Pharmacotherapy of Stroke By Tolcha.R
- 18. Diagnosis • Ischemic andhemorrhagic events have similar symptoms and must be distinguished before initiating treatment • Laboratory tests – Laboratory tests for hypercoagulable states should be done only when the cause of the stroke cannot be determined • Protein C, protein S, and antithrombin III • Antiphospholipid antibodies 9/23/2021 18 Pharmacotherapy of Stroke By Tolcha.R
- 19. Cont… • Imaging Studies –Computed tomography (CT) head scan – Magnetic resonance imaging (MRI)of the head will reveal areas of ischemia with higher resolution and earlier than the CT scan. – Diffusion-weighted imaging will reveal an evolving infarct within minutes 9/23/2021 19 Pharmacotherapy of Stroke By Tolcha.R
- 20. Desired Outcome • Thegoals of treatment for acute stroke are to: – reduce the ongoing neurologic injury and decrease mortality and long-term disability – Prevent complications secondary to immobility and neurologic dysfunction – prevent stroke recurrence 9/23/2021 20 Pharmacotherapy of Stroke By Tolcha.R
- 21. Treatment General Approach • Theinitial approach is – to ensure adequate respiratory and cardiac support and – to determine quickly whether the lesion is ischemic or hemorrhagic based on a CT scan. • Ischemic stroke patients presenting within hours of symptom onset should be evaluated for reperfusion therapy 9/23/2021 21 Pharmacotherapy of Stroke By Tolcha.R
- 22. Cont… • Blood PressureControl – Elevated blood pressure should remain untreated in the acute period (first 7 days) after ischemic stroke because of the risk of decreasing cerebral blood flow and worsening symptoms. – The pressure should be lowered if it exceeds 220/120 mm Hg or there is evidence of aortic dissection, acute myocardial infarction, pulmonary edema, or hypertensive encephalopathy. – If blood pressure is treated in the acute phase, short-acting parenteral agents (e.g., labetalol, nicardipine, nitroprusside) are preferred. 9/23/2021 22 Pharmacotherapy of Stroke By Tolcha.R
- 23. Cont… • Patients withhemorrhagic stroke should be assessed – to determine whether they are candidates for surgical intervention via an endovascular or craniotomy approach. • After the hyperacute phase has passed, attention is focused on – preventing progressive deficits – minimizing complications and – instituting appropriate secondary prevention strategies 9/23/2021 23 Pharmacotherapy of Stroke By Tolcha.R
- 24. Supportive Therapy IV fluids- Avoid excessive fluid administration - NS at 50 ml/h Blood glucose - Treat hypoglycemia with D50 - Treat hyperglycemia with insulin if Glu > 200mg/dl Oral intake - NPO initially until swallowing assessed Oxygen - Supplement if indicated (SaO2 <90%) Temperature - Oral or rectal APAP as needed (T > 100.4°F) 24
- 28. Secondary prevention ofstroke • Prevention of stroke in patient who history of TIA – Statin – BP management – Diabetes management – Cardiovascular disorder management Clopidogrel is as effective and safe as aspirin. Clopidogrel is an alternative to aspirin in secondary prevention of stroke. 9/23/2021 Pharmacotherapy of Stroke By Tolcha.R 28
- 29. Treatment Pharmacologic Therapy ofIschemic Stroke • AHA Stroke Council guidelines for the management of acute ischemic stroke give grade A recommendations to only two pharmacologic therapies: – IV tissue plasminogen activator (alteplase) within 3 hours of onset – Aspirin within 48 hours of onset 9/23/2021 29 Pharmacotherapy of Stroke By Tolcha.R
- 30. IV tissue plasminogenactivator Alteplase • initiated within 3 hours of symptom onset has been shown to reduce the ultimate disability due to ischemic stroke. • A head CT scan must be obtained to rule out hemorrhage before beginning therapy. • The patient must also meet specific inclusion criteria and no exclusionary criteria • The dose is 0.9 mg/kg (maximum 90 mg) infused IV over 1 hour after a bolus of 10% of the total dose given over 1 minute. 9/23/2021 30 Pharmacotherapy of Stroke By Tolcha.R
- 31. Cont… 9/23/2021 31 Pharmacotherapy ofStroke By Tolcha.R
- 32. Anti-platelets/Anticoagulants • Anticoagulant andantiplatelet therapy should be avoided for 24 hours, and the patient should be monitored closely for hemorrhage. • Aspirin – 50 to 325 mg/day started between 24 and 48 hours after completion of alteplase – has also been shown to reduce long-term death and disability. • The AHA/ASA guidelines recommend that – antiplatelet therapy as the cornerstone of antithrombotic therapy for the secondary prevention of ischemic stroke and – should be used in noncardioembolic strokes. 9/23/2021 32 Pharmacotherapy of Stroke By Tolcha.R
- 33. Cont… • Aspirin, clopidogrel,and extended-release dipyridamole plus aspirin are all considered first-line antiplatelet agents • The combination of aspirin and clopidogrel can only be recommended in patients with – ischemic stroke and a recent history of myocardial infarction or coronary stent placement and – only with ultra-low-dose aspirin to minimize bleeding risk. • Warfarin – the antithrombotic agent of first choice for secondary prevention in patients with atrial fibrillation and a presumed cardiac source of embolism. 9/23/2021 33 Pharmacotherapy of Stroke By Tolcha.R
- 34. Cont… • Blood PressureControl – Elevated blood pressure is common after ischemic stroke – its treatment is associated with a decreased risk of stroke recurrence. – The JNC and AHA/ASA guidelines recommend an ACEI and a diuretic for reduction of blood pressure in patients with stroke or TIA after the acute period (first 7 days). – ARBs can be used in patients unable to tolerate ACEIs 9/23/2021 34 Pharmacotherapy of Stroke By Tolcha.R
- 35. Cont… • The NationalCholesterol Education Program considers ischemic stroke or TIA to be a coronary risk equivalent and recommends – the use of statins in ischemic stroke patients to achieve an LDL< 100 mg/dL. • LMWH or low-dose subcutaneous UH (5,000 units twice daily) is recommended – for prevention of DVT in hospitalized patients with decreased mobility due to stroke and should be used in all but the most minor strokes. 9/23/2021 35 Pharmacotherapy of Stroke By Tolcha.R
- 36. 9/23/2021 Pharmacotherapy ofStroke By Tolcha.R 36
- 37. Cont… 9/23/2021 37 Pharmacotherapy ofStroke By Tolcha.R
- 38. Treatment Pharmacologic Therapy ofHemorrhagic Stroke • There are currently no standard pharmacologic strategies for treating intracerebral hemorrhage. • Medical guidelines in acutely ill patients in neurointensive care units should be followed for managing – blood pressure – increased intracranial pressure and – other medical complications 9/23/2021 38 Pharmacotherapy of Stroke By Tolcha.R
- 39. Cont… • Subarachnoid hemorrhagedue to aneurysm rupture is – associated with a high incidence of delayed cerebral ischemia in the 2 weeks after the bleeding episode. • Vasospasm of the cerebral vasculature is – thought to be responsible for the delayed ischemia and occurs between 4 and 21 days after the bleed. 9/23/2021 39 Pharmacotherapy of Stroke By Tolcha.R
- 40. Cont… • The calciumchannel blocker nimodipine – is recommended to reduce the incidence and severity of neurologic deficits resulting from delayed ischemia. – Nimodipine 60 mg every 4 hours should be initiated on diagnosis and continued for 21 days in all subarachnoid hemorrhage patients. – If hypotension occurs, it can be managed by • reducing the dosing interval to 30 mg every 2 hours (same daily dose) • reducing the total daily dose (30 mg every 4 hours) and • maintaining intravascular volume and pressor therapy. 9/23/2021 40 Pharmacotherapy of Stroke By Tolcha.R
- 41. Blood on CT (orMRI) SAH ICH Yes No Meet t-PA criteria Yes Time of onset <3 hours Spontaneous improvement or resolution of symptoms No Neurosurgical consultation Yes IV t-PA per NINDS protocol No Hydration with NS; BP management; correct glucose disturbance; hyperglycemia; consider O2 Consider neurosurgical consultation, especially if cerebellar ICH and/or intraventricular blood Antithrombotic therapy after 24 hours; stroke etiology evaluation Hydration with NS; BP management; correct glucose disturbance; hyperglycemia; consider O2 Antiplatelets; anticoagulants (if needed); stroke etiology evaluation No 41
- 42. Rehabilitation American Stroke Associationguidelines focus on: • Managing co-morbidities • Training for maximum independence • Facilitating maximum psychosocial coping and adaptation by patient and family • Preventing secondary disability • Enhancing quality of life • Preventing recurrent stroke 42 9/23/2021 Pharmacotherapy of Stroke By Tolcha.R 42
- 43. Evaluation Of Therapeutic Outcomes •Patients with acute stroke should be monitored intensely for the development of – neurologic worsening – Complications and – adverse effects from treatments 9/23/2021 43 Pharmacotherapy of Stroke By Tolcha.R
- 44. Cont… 9/23/2021 44 Pharmacotherapy ofStroke By Tolcha.R
- 45. Clinical Case QUESTION 1:R.B. is a 60-year-old, 5 feet 6 inches tall, 85-kg woman who is concerned about having a stroke. Her father died of a stroke, and her 85-year-old mother has had several episodesdiagnosed as TIAs. R.B.’s blood pressure is 140 to 150/90 to 100 mm Hg, and she was recently diagnosed with diabetes mellitus. She does not have a history of TIA or stroke. Additionally, she smoked for 25 years but has not used tobacco for the past 10 years. Her current medications include lisinopril, metformin, conjugated estrogen/medroxyprogesterone, and acetaminophen. She approaches her pharmacist because of concerns about having a stroke and being “like her parents.” What can R.B. do to reduce her risk of stroke? 9/23/2021 Pharmacotherapy of Stroke By Tolcha.R 45
- 46. • QUESTION 1:P.C., a 65-year-old man (100 kg, 5 feet 9 inches), is admitted through the emergency department (ED) with right-sided weakness. As per report the patient was last seen well around 8:30 PM by his wife. Around 9:15 PM, the patient’s son heard a bump and went upstairs to find his father on the floor. The patient had a slurred speech and had a right facial droop. At this point 911 was called and patient arrived at 9:45 PM to ED. He regained consciousness by the time he arrived in the ED. Both right extremities are flaccid. He is unable to speak but is capable of understanding instructions (i.e., expressive aphasia). Gross ophthalmologic examination indicates right-sided neglect (inability of his eyes to track to the right or acknowledge the right side of his body). His blood pressure is 165/95 mm Hg; other vital signs are normal. Laboratory studies are all within normal limits. What interventions should have been initiated before arrival in the ED? 9/23/2021 Pharmacotherapy of Stroke By Tolcha.R 46
- 47. What diagnostic testsand evaluations will be helpful in guiding P.C.’s therapy? 9/23/2021 Pharmacotherapy of Stroke By Tolcha.R 47
- 48. 9/23/2021 Pharmacotherapy ofStroke By Tolcha.R 48
- 49. 9/23/2021 Pharmacotherapy ofStroke By Tolcha.R 49
- 50. Thank You! 9/23/2021 Pharmacotherapyof Stroke By Tolcha.R 50