Therapeutics I Exam IV (Stroke Only) Flashcards
Ischemic, Hemorrhage, and Subarachnoid
Which non-DHP CCB has a greater effect on calcium channels?
Verapamil
This medication also moderately blocks alpha receptors.
What is a big contraindication for the use of non-DHP CCBs like Verapamil and Diltiazem?
Do not use in patients with heart failure or post-MI patients.
What is cerebral blood flow (CBF)?
This is the volume of blood that passes through a specific quantity of the brain tissue during a period of time.
50mL/100 g of brain tissue/minute
What is intracranial pressure (ICP)?
This pressure within the craniospinal compartment (normally 5-10 mmHg)
What is cerebral profusion pressure?
This is the net pressure gradient that drives oxygen delivery to cerebral tissue. Normally 60-80 mmHg.
What is the Monroe-Kelli Doctrine?
The Monroe-Kellie Doctrine states that the sum of the volumes of the brain, cerebrospinal fluid (CSF), and blood in the skull is constant. This means that if the volume of one of these components increases, the volume of one or both of the others must decrease.
What is an EEG?
This is a recording of summed electrical activity within the brain via the placement of electrodes.
What is a CT scan?
This is a fast series of x-rays put together to create images of an area.
What is an MRI?
This is when a strong magnetic field takes pictures of the inside of the body.
What is pupillometry?
These tests evaluate brain stem reflexes and optic/oculomotor nerves.
What is transcranial Dopplers (TCD’s)?
This is an ultrasound that monitors cerebral blood flow velocity. Often used to look for vasospasms.
What are intraparenchymal bolts?
This is when a sterile catheter is advanced through the skull into the dura right into the right frontal region of the brain. It only measures intracranial pressure.
Intraparenchymal bolts only measure _______________ pressure.
Intracranial
What is an external ventricular drain (EVD)?
This is when a sterile catheter is advanced through the skull, dura, and brain parenchyma into the ventricles. It drains CSF and/or infection/blood as well as measures intracranial pressure
What are the two functions of an external ventricular drain (EVD)?
- Drains CSF (or blood/infection)
- Measure intracranial pressure
What guidelines are used for stroke decision making in pharmacy?
AHA/ASA guidelines
What are the two types of strokes?
A. Acute ischemic stroke (AIS)
B. Acute spontaneous intracranial hemorrhage (ICH)
What is the difference between a transient ischemic attack (TIA) and an acute ischemic stroke?
A TIA is a temporary blockage of blood flow to the brain but symptoms only last around 5 minutes as the clot dissolves on its own.
_____________ score estimates risk of stroke after a suspected TIA.
ABCD2
Are more strokes ischemic or hemmorrhagic?
Ischemic (87%)
What are the 8 different possible causes for a stroke?
- Atherosclerosis
- Vascular Malformation
- Arrhythmia
- Hyper coagulable state
- Small vessel disease
- Congenital heart disease
- genetic disorder
- Unknown
What is the mnemonic the remember the presentation of a stroke?
BEFAST
Balance (unbalanced)
Eyes (blurred)
Face (drooping)
Arms (unable to lift)
Speech (slurred)
TIME (CALL 911)
What is the scale used to determine the severity of a stroke?
NIHSS scale (not sure if we actually need to memorize how to score or just the numbers)
What scale is used to determine the severity of an acute ischemic stroke?
ASPECTS
What is the time window in which thrombolytics can be given in cases with acute ischemic stroke?
Within 3-4.5 hours of the symptoms
What is the function of T-Pa?
T-Pa activates plasminogen to plasmin which goes into and breaks down fibrin to degrade a clot.
What is the dosing for Tenecteplase in cases is acute ischemic stroke?
0.25 mg/kg
What is maximum dose of Tenecteplase in the case of acute ischemic stroke?
25 mg
What is the dosing for Alteplase in cases of acute ischemic stroke?
0.9 mg/kg
What is the maximum dose of alteplase in the case of acute ischemic stroke?
90 mg
Does Tenecteplase or Alteplase have a longer half life?
Tenecteplase with a half life of 90-130 minutes. Alteplase is 5 minutes.
Tenecteplase is incompatible with _________ bolus over 5-10 seconds.
Dextrose
When giving alteplase, the first ______% must be given as a bolus while the rest is given as a continuous infusion over _________ hours.
10%
2 hours
How often must patients be monitored after receiving a fibrinolytic?
- Every 15 minutes for the first 2 hours
- Every 30 minutes for the next 6 hours
- Every hour until the 24 hour mark
What are the ABSOLUTE contraindications for fibrinolytic use?
Intracranial hemorrhage
Cerebral vascular malformation
Acute ischemic stroke within the last 3 months
Head injury in last 3 months
Aortic dissection
Active bleeding
Recent intracranial or spinal surgery
On anticoagulants (INR >1.7 on warfarin)
Active endocarditis
What are the relative contraindications for fibrinolytic use?
Poorly managed HTN
Prolonged CPR
Major surgery within the last 3 weeks
History of acute ischemic stroke
Dementia
Internal bleeding within the last 2-4 weeks
Pregnancy
Peptic ulcer
Recent lumbar puncture
NIHSS > 25
Coagulopathy
Those who are candidates for thrombolytics with acute ischemic stroke must arrive to the hospital within _______-________ hours of their stroke.
3-4.5 hours
What are the 3 things patients must have in order to be a fibrinolytic candidate?
-last known ‘well’ was within 3-4.5 hours from arrival
- no contraindications
- BP less than 180/110
If a patient is a candidate for fibrinolytics but their BP is above 180/110, what 3 medications can be used to reduce BP before giving the fibrinolytic?
Nicardipine
Clevidipine
Labetalol
What is the IV dosing for Nicardipine?
1-15 mg /hr
What is the IV dosing for Clevidipine?
1-21 mg/hr
Between Nicardipine, Clevidipine, and Labetalol, which one has the fastest onset?
Nicardipine (1-2 minutes)
Between Nicardipine, Clevidipine, and Labetalol, which one has the fastest half-life?
Clevidipine (1 minute)
What is the dosing for labetalol?
10-20 mg over 1-2 minutes
The blood pressure goal for those presenting with acute ischemic stroke is less than ______/______.
180/110 mmHg
What is an endovascular thrombectomy?
This is a minimally invasive procedure that removes blood clots (thrombi) from blood vessels using a catheter
In order to be a candidate for a thrombectomy, what 3 criteria within the brain must be met?
- Infarct volume less than 70 mL
- Ratio of ischemic tissue to initials infarct volume of 1.8 or more
- penumbra greater than 15 mL
In order to be a candidate for a thrombectomy, what 2 criteria within the patient must be met?
- Within 24 hours of last known ‘well’
- Large vessel occlusion in either middle cerebral artery, internal carotid artery, or basilar artery
What is an infarct core?
This is the brain tissue that has already died and cannot be reversed due to the stroke.
What is the penumbra?
This area surrounds the infarct core and is at high risk of dying but damage is reversible here.
What is the oligemi?
This is areas of hypoperfusion surrounding the infarct core and penumbra. This area will recover without treatment.
T or F: It is fairly normal for patients with acute ischemic stroke to receive both fibrinolytic and a thrombectomy.
True.
In order for a patient to be a candidate for a thrombectomy, what 3 vessels could be blocked?
Middle cerebral artery
Internal Carotid artery
Basilar artery
If the thrombolytic is not working well, ________________ can be added on.
Antiplatelets including GpIIb/IIIa inhibitors like Tirofiban and Eptifibatide or P2Y12 inhibitor like Cangrelor.
What is a decompressive hemicraniectomy?
This is when a large flap of skull is removed and the dura remains open in order to relieve pressure on the brain.
In order to be eligible for a decompressive hemicraniectomy, patients must be between the ages of _______-_______ years and have at least ________ of territory infarcted.
18-60 years
2/3rds
What are massive complications associated with acute ischemic strokes?
Possible hemorrhagic conversion, brain edema, UTIs, VTEs, and pneumonia
In order to prevent hemorrhagic conversion following an acute ischemic stroke, blood pressure should be kept below ______/_____ if the patient had ____________ therapy.
180/105
Reperfusion
What 2 things increase the risk for hemorrhagic conversion following an acute ischemic stroke?
Bigger strokes (NIHSS >20) and reperfusion therapy
Why is pneumonia a major complication following an acute ischemic stroke?
Stroke patients often have dysphagia after a stroke and aspirate things into the lungs leading to pneumonia.
What is the 3rd leading cause of death following a stroke?
Pneumonia
__________ ________ accounts for 10% of deaths following a stroke.
Pulmonary embolism
How are VTEs (DVT/PE) prevented during stroke treatment?
Think prophylaxis anticoagulation here:
-5000 Units unfractionated heparin TID
-Enoxaparin 40 mg SubQ daily
What is the key thing to prevent VTEs following a stroke?
Early mobilization
What is the black box warning for prasugrel?
Fatal bleeding in those with history of TIA or stroke
What are the things that need to be checked in a patient after getting care for a stroke in order to find the cause of the stroke?
- Lipid level check for atherosclerosis
- PFO check (hole in heart)
- Intracranial atherosclerotic disease (ICAD) check
- EKG check for possible arrhythmia
- Glucose + HbA1c for diabetes
- BP for hypertension check
- smoking habits
- Hypercoagulablility testing
T or F: Clopidogrel is not a prodrug.
False. Clopidogrel is a prodrug
What is the dosing for the irreversible P2Y12 inhibitor anti platelet, clopidogrel?
Loading dose: 300-600 mg
Then 75 mg daily
What is the dosing for Ticagrelor?
Loading dose: 180 mg
Then 90 mg BID
What are the 3 antiplatelets typically used following a stroke?
Clopidogrel, ticagrelor, and/or aspirin
A ___________ _____ scan is needed to exclude intracranial hemorrhagic stroke before giving IV TPA.
Noncontrast CT
For those with intracranial atherosclerotic disease following a stroke, AHA guidelines state that _________ at doses of ________ mg per day is the superior antiplatelet for this population.
Aspirin
325 mg/day
___________ mg of ___________ decreased overall incidence of stroke and cardiovascular events.
80 mg of atorvastatin
T or F: Most stroke patients should be on a high intensity statin like atorvastatin 80mg or rosuvastatin 40 mg.
True.
Ticagrelor efficacy is reduced when used in combination with aspirin doses greater than __________ mg.
100 mg
If a person who had a acute ischemic stroke and also has a atrial fibrillation/flutter, what 3 anticoagulants could be used?
Warfarin, apixaban, or rivaroxaban
Before initiating any anticoagulants after an acute ischemic stroke, a time period of _____-______ days must be waited.
4-14 days all dependent on stroke size
What is the dosing for apixaban for atrial fibrillation following an acute ischemic stroke?
5 mg PO BID
What is the dosing for rivaroxaban for atrial fibrillation following an acute ischemic stroke?
20 mg daily
After giving thrombolytics or endovascular therapy, the systolic blood pressure goal is between _________-_________ mmHg for those with acute ischemic stroke.
130-180 mmHg
If a person receives no treatment following their acute ischemic stroke (ie; they got to the hospital too late), what is their blood pressure goal?
Less than 220/110 mmHg for 48-72 hours. This is letting the body naturally regulate
For any form of treatment or no treatment, what is the blood pressure goal for everyone that was treated for an acute ischemic stroke after 72 hours?
140/90 mmHg
If higher, initiate blood pressure lowering agents
T or F: Secondary prevention is key for preventing future strokes.
True
What is a hemorrhagic stroke?
This is bleeding into the brain tissue or parenchyma (functional brain tissue)
What are some things that increase the risk for a hemorrhagic stroke?
Aneurysms, AV malformations, tumors, angiopathy, coagulopathy, trauma, on anticoagulants
Hemorrhagic strokes make up ____-_____% of all strokes.
10-15%
What are the two hemorrhagic type strokes discussed in class?
Intracerebral/ Parenchymal hemorrhage
Subarachnoid hemorrhage
What are typical causes of intracranial hemorrhages?
Trauma or spontaneous
What are modifiable risk factors that increase the likelihood of getting an intracranial hemorrhage?
Hypertension
Coagulopathy (impaired clot formation)
Current smoker
Excessive alcohol (alcohol is blood thinner)
Diabetes
Sympathomimetic and illicit drug use
What are nonmodifiable risk factors that increase the risk for intracranial hemorrhage?
Prior intracranial hemorrhage
Advanced age
Male sex
Non-white ethnicity
Cerebral amyloid angiopathy
CKD
Congenital coagulopathy
Tumor
Vascular abnormalities
Do ischemic and hemorrhagic strokes have similar symptoms?
Yes! Both types will present with BEFAST
What tool is used to evaluate the severity of an intracranial hemorrhage?
ICH Score
What is desmopressin?
Medication that increases Von Willebrand factor receptors so that platelet aggregation can be increased.
A patient presents with an intracranial hemorrhage and is on anticoagulants. What is the first thing to be done once this information is uncovered?
Discontinue to anticoagulant. Based on the anticoagulant type, may need to administer the antidote to stop bleeding.
A patient presents with an intracranial hemorrhage and is on warfarin. What should be done next?
- STOP THE WARFARIN
- MEASURE INR
A. INR 1.3-1.9: give 4F PCC 10-20 IU/kg
B. INR >2: give 4F PCC 25-50 IU/kg - GIVE VITAMIN K
A person on warfarin presents with ICH. At what INR range would they receive 10-20 IU/kg of 4-factor PCC (and vitamin K of course)?
1.3-1.9 INR
A person on warfarin presents with ICH. At what INR range would they receive 25-50 IU/kg of 4-factor PCC (and vitamin K of course)?
INR of 2 or greater
A patient presents with an intracranial hemorrhage and is on dabigatran. What should be done next?
- Figure out when dose was last taken
- If taken within the last 2 hours: GIVE ACTIVATED CHARCOAL
- Longer than 2 hours: Give Idarucixumab
A patient presents with an intracranial hemorrhage and is on an Xa-inhibitor like rivaroxaban or apixaban. What should be done next?
- Figure out when dose was last taken
- If taken within the last 2 hours: GIVE ACTIVATED CHARCOAL
- Longer than 2 hours: Give andexanet alfa (if not available can use 4F PCC)
A patient presents with an intracranial hemorrhage and is on unfractionated heparin. What should be done next?
- STOP HEPARIN
- Give protamine
A patient presents with an intracranial hemorrhage and is on LMWH like dalteparin or enoxaparin. What should be done next?
- STOP THE LMWH
- Give protamine
A patient presents with an intracranial hemorrhage and is on an antiplatelet like clopidogrel or aspirin. What should be done next?
There is no specific reversal agent for anti-platelet agents unfortunately. If the patient HAS to undergo rapid intervention, can initiate platelet transfusion.
T or F: Desmopressin is proven to be an adequate agent for antiplatelet reversal.
False. It is unknown if desmopressin with platelet transfusions decreases hematoma size.
If the patient is not on anticoagulants or antiplatelets and just had the most random ICH, what is the last treatment option?
Tranexamic acid (TXA)
What is the MOA of tranexamic acid?
Tranexamic acid is a synthetic derivative of lysine that exerts antifibrinolytic effects by blocking lysine binding sites on plasminogen molecules, inhibiting the interaction of plasminogen with formed plasmin and fibrin. All this does is stabilizes the clot.
Managing _______ _________ for an ICH patient is crucial to their recovery.
Blood pressure
Blood pressure treatment for those presenting with ICH needs to be initiated with ______ hours of hospital arrival.
2 hours
What is the systolic blood pressure goal for those with ICH?
Systolic between 130-150
T or F: Even though the goal for systolic blood pressure in ICH patients is 130-150, going below 130 mmHg improves outcomes.
False. Reducing systolic BP below 130 may be harmful as the brain is not getting perfused.
What are the two main agents used to control blood pressure in ICH patients?
Typically use Nicardipine or Clevidipine as there is not too much variability in blood pressure with these DHP CCBs.
What is the dosing for Nicardipine in terms of blood pressure regulation?
0-15 mg/hour
What is the half-life of nicardipine?
3 minutes
What is the dosing for Clevidipine?
0-21 mg/hour
What is the half-life for clevidipine?
1 minute
If a patient presents with an ICH and is on any type of anticoagulant, rapid reversal (assuming applicable), needs to be initiated within ________ hour of arrive.
1 hour
If a DOAC or dabigatran was taken within the last _______ hours of arrival, give activated charcoal.
2 hours
T or F: Platelet transfusion are only indicated if a patient needs emergency surgery.
True. Giving platelets if a patient is on an antiplatelet but does not need surgery is not indicated in the guidelines.
For warfarin reversal, 4F PCC is given. What is this medication?
4F PCC is also called KCENTRA. It replaces factors II, VII, IX, and X, as well as protein C and S.
Warfarin reversal includes giving 4F PCC and _________________ via IV push.
Vitamin K
What is the reversal agent for DOACs like rivaroxaban and apixaban?
Andexanet alfa
What is the reversal agent for dabigatran?
Idarucizumab (Praxbind)
What is the MOA of andexanet alfa?
This is the reversal agent for DOACs. It works by being a factor Xa decoy molecule that sequesters the DOACs and prevents them from inhibiting the real factor Xa.
What is the MOA for idarucizumab (Praxbind)?
It is a monoclonal antibody that binds and inhibits dabigatran itself.
What is the MOA of protamine?
Protamine reverses heparins. Protamine is a highly alkaline protein molecule with a + charge that binds heparin which is - charged.
Why is the maximum dose for protamine 50 mg?
At doses higher than 50 mg, protamine turns into an anticoagulant.
What are the 4 things that go into secondary prevention following an intracranial hemorrhagic stroke?
- Finding underlying cause
- Glucose control
- Seizure management
- Surgical management (external ventricular drain)
What is the surgical management for a spontaneous ICH with obstructive hydrocephalus?
External ventricular drain placement
What is the surgical management for a spontaneous ICH with less than 30mL of blood collected and a GCS greater than 3?
External ventricular drain with possible small amount of thrombolytic placed into the stroke site within the brain.
What is the surgical management for a spontaneous ICH with less than 30 mL of blood collected?
Possible neuroendoscopy with an external ventricular drain placed and a small amount of thrombolytic placed at the brain site of injury.
What are the 5 common complications associated with ICH?
Expansion of hemorrhage
Seizures (no seizure prophylaxis tho)
cerebral edema
Hydrocephalus
VTE
When would we restart an ICH patient on their anticoagulants for VTE prophylaxis?
24 hours following the last stable CT scan
T or F: Most subarachnoid hemorrhages are nonspontaneous.
False. Most are spontaneous
Having a subarachnoid hemorrhage is actually really bad because of what anatomical freature?
This section of the protective layers of the brain actually houses most of the cerebral arteries.
What are nonmodifiable risk factors that increase the risk of developing an aneurysm?
Family history
Connective tissue disorders
polycystic kidney disease
Injury
What are the risk factors that increase the risk for a ruptured aneurysm?
Hypertension
smoking
alcohol abuse
Race
sympathomimetic drugs
Aneurysm greater than 7 mm
What is the hallmark presentation of a subarachnoid hemorrhage?
Worst headache of entire life
T or F: An aneurysm leads to a hemorrhage.
True
What is the most common cardiac arrhythmia?
Atrial Fibrillation
What scoring tool evaluates the risk for vasospasm after a subarachnoid hemorrhage?
Modified Fischer Scale
What are the different ways to diagnose a subarachnoid hemorrhage?
Noncontrast head CT or a lumbar puncture
What is the blood pressure goal for someone with an unsecured aneurysm?
SBP less than 160, but 130-140 is the real goal!!!
What is the systolic blood pressure goal for someone with a secured aneurysm?
SBP 130-160
If a patient with a subarachnoid hemorrhage is on anticoagulants, what is the first thing to do?
STOP THE ANTICOAGULANT AND GIVE REVERSAL AGENT PER ICH GUIDELINES
Is it reasonable to consider antifibrinolytic therapy (TXA) for acute management in subarachnoid hemorrhage?
Yes. Note that the results when using TXA in a subarachnoid hemorrhage is not that beneficial.
What are the two ways in which an aneurysm can be secured?
Clip or coil
What are the complication associated with subarachnoid hemorrhage?
Vasospasm which lead to delayed cerebral ischemia
Rebleeding
Seizures ( prophylaxis here)
Hydrocephalus
Medical issues like pneumonia
___________ __________ is a type of ultrasound that can see vasospasm.
Transcranial dopplers
What scoring tool is used to evaluate the risk for vasospasms?
Modified Fischer scale
How are vasospasm managed in patients following a subarachnoid hemorrhage?
Nimodipine 60 mg Q4H for 21 days
What is the MOA of Nimodipine?
It is a calcium channel blockers that improves delayed ischemic neurological deficit but not the actual vasospasm.
What is a side effect associated with Nimodipine?
Hypotension
T or F: For both ischemic and hemorrhagic strokes, VTE prophylaxis should be resumed as soon as possible.
True (24 hours after a clean CT scan)
It is important to maintain ______________ for a patient while they are on Nimodipine.
Euvolemia
If delayed cerebral ischemia is suspected, what can be done?
Pressors can be given to increase blood pressure to open up those shut vessels and increase perfusion.
T or F: 80% of patients with permanent atrial fibrillation have an identifiable underlying casue.
True
T or F: 1 in 6 strokes occurs in patients with atrial fibrillation.
True
What scoring tool estimates the survivability based on symptoms for a subarachnoid hemorrhage?
Hunt and Hess Scoring tool
What is an aneurysm?
It is a weak or thin spot on an artery in the brain that bulges out and fills with blood. Majority of these forms in major arteries along the base of the skull. They can range from 1/8 inch to a full inch.
Which of the following is NOT an absolute contraindication for thrombolytic therapy in acute ischemic stroke?
A) Active endocarditis
B) Aortic dissection
C) Prior ischemic stroke within the last 6 months
D) Intracranial hemorrhage
C. Prior ischemic stroke within the last 6 months (It must be within the last 3 months for absolute contraindication.)
What is the primary mechanism of action of tenecteplase in stroke management?
A) Direct thrombin inhibition
B) Fibrin-specific activation of plasminogen
C) Inhibition of Factor Xa
D) Reversible blockade of P2Y12 receptors
B. Fibrin-specific activation of plasminogen. Plasmin then go in and breaks down fibrin holding the clot together
A patient presents with an acute ischemic stroke with an NIHSS score of 15 and a middle cerebral artery occlusion. According to thrombectomy guidance, which of the following criteria must be met to proceed with mechanical thrombectomy?
A) Infarct volume < 100 mL
B) Infarct volume < 70 mL
C) ASPECTS score ≤ 3
D) NIHSS < 6
B) Infarct volume < 70 mL
In a patient with acute ischemic stroke who has not received thrombolytic therapy, which of the following is the target blood pressure goal?
A) SBP < 220/110 mmHg
B) SBP < 140/90 mmHg
C) SBP < 180/110 mmHg
D) SBP < 160/80 mmHg
C) SBP < 180/110 mmHg
Which of the following statements regarding anticoagulation reversal in intracerebral hemorrhage (ICH) is TRUE?
A) Andexanet alfa is the first-line reversal agent for dabigatran.
B) Idarucizumab is used to reverse the effects of Factor Xa inhibitors.
C) 4F-PCC (Kcentra) is used to reverse warfarin-induced coagulopathy.
D) Activated charcoal is recommended for all cases of anticoagulation-related ICH.
C) 4F-PCC (Kcentra) is used to reverse warfarin-induced coagulopathy.
Which of the following patients is most likely to benefit from nimodipine therapy?
A) A patient with acute ischemic stroke undergoing thrombectomy
B) A patient with subarachnoid hemorrhage at risk for vasospasm
C) A patient with a large hemorrhagic stroke and elevated ICP
D) A patient with hypertensive crisis leading to intracerebral hemorrhage
B) A patient with subarachnoid hemorrhage at risk for vasospasm
In patients with atrial fibrillation-related ischemic stroke, when is it generally recommended to initiate anticoagulation post-stroke?
A) Immediately upon presentation
B) Within 24 hours
C) Between 4-14 days, depending on stroke severity
D) Only after 30 days to reduce hemorrhagic risk
C) Between 4-14 days, depending on stroke severity
T or F: Administration of aspirin 325mg is recommended in patients with acute ischemic stroke within 24-48 hours after onset of the stroke.
True
T or F: For those presenting with minor ischemic strokes (NIHSS less than 3 or less) who did not receive fibrinolytics should be started on dual platelet therapy of aspirin and clopidogrel within 24 hours after symptoms onset and continued for 21 days and up to 90 days.
True
