Seizures/ Epilepsy Flashcards
Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
Seizure: a sudden, uncontrolled surge of excitatory neuronal activity within the brain.
Epilepsy: a chronic seizure disorder.
(EEG)-electroencephalogram- records electrical activity within the brain.
- can be used to identify abnormal firing patterns.
- very useful in the outpatient and inpatient care settings.
-
-
- fever
- infection
- alcohol withdrawal
- hypoglycemia
- electrolyte abnormalities
- head injury
- drug induced
Key drugs that can lower the seizure threshold:
“if a patient has a past history of epilepsy, we want to avoid these medications”
- if patient has a drug induced seizure, we want to know what drug to look for!
Theophylline, Varenicline, acyclovir, valacyclovir, metoclopramide
[analgesics]
opioids - (tramadol, meperidine) *
[anti-infectives]
- quinolones, carbapenems, cephalosporins, penicillin’s*, lindane, mefloquine
[psychiatric medications]
- bupropion, antipsychotics: clozapine, lithium, tricyclic antidepressants,
—————————————————————————————————————
- patients on High doses of these drugs or have renal impairment are at an even greater risk of having a seizure
First Aid for Seizures:
1) Prevent injury by clearing the area around the person of anything hard or sharp.
2) Ease the person to the floor and put something soft and flat, like a folded jacket, under the head. Turn the person gently onto one side. This will help keep the airway clear.
3) Remove eyeglasses and loosen ties or anything around the neck that may make breathing difficult.
4) Time the seizure. If the seizure continues for longer than 5 minutes without signs of slowing down, or if the person has trouble breathing, appears to be injured, in pain or has an unusual recovery, call 911.
5) Do not hold people down or try to stop their movements.
6) Contrary to popular belief, it is not true that people having a seizure can swallow their tongue. Do not put anything in the person’s mouth.
7) Do not attempt artificial respiration except in the unlikely event that a person does not start breathing after the seizure has stopped.
Classification of Seizures:
- one way to classify seizures is based off of where they start in the brain [LOCATION].
- seizures can occur in a part of the brain, one side of the brain (focal) or they can occur across the entire brain (generalized).
Focal Seizures: occur on one side of the brain and can spread to the other side.
Generalized Seizures: start on both sides of the brain.
Classification of Seizures:
- another way to classify seizures is based on the [SYMPTOMS] the patient has during the active seizure.
- seizures patients have, can have certain (MOTOR symptoms) during an active seizure.
(motor symptoms)
- uncontrolled jerking movements
- muscle twitching
- rigid or tense muscles
- limp
Tonic = rigid Tense muscles
Clonic = unControlled jerking movements
Myoclonus = brief Muscle twitching
Atonic = limp (no tone)
Classification of Seizures:
- seizures patients have, can have certain (Non-MOTOR symptoms) during an active seizure.
- Awareness/consciousness of the active seizure
OR
- Loss of consciousness/unaware of the active seizure
Focal seizures are classified based on this level of awareness.
Focal aware seizures:
- no loss of consciousness.
- so patients are aware they are seizing
- previously known as “simple partial seizure”
Focal seizures with impaired awareness:
- means patient has a loss of consciousness
- patient not aware they are seizing
- previously known as “complex partial seizures”
Generalized seizures with non-motor symptoms are referred to as _________________.
absence seizures
-typically include starring spells with no movement.
Acute Seizure Management:
seizures can vary by -
1)
2)
3)
1) Type
2) Duration
3) Treatment options
Acute Seizures:
There are 2 types-
1) typical Seizures
Duration: - self-limiting, lasts a couple minutes at most, less than < 5min
Treatment: - treatment may or may not be needed.
2) (SE) Status Epilepticus
Duration: - lasts greater than or equal to > 5min
Treatment: - emergency care = can be FATAL
both differ in how long they last and how we approach treating them.
Status epilepticus - is a seizure that lasts 5 minutes or more because the normal mechanisms that terminate seizures are not working.
- this is a medical emergency and emergency treatment should be given with any seizure that lasts longer than 5 minutes.
- negative consequences include causing cardiac arrhythmias, hypoxia, and permanent cognitive or neurological damage.
- can be fatal
Status Epilepticus treatment:
- Is divided into phases
1)
2)
3)
4)
1) Stabilization phase (0-5 minutes)
2) Initial Treatment Phase (5-20 minutes)
3) Second Treatment Phase (20-40 minutes)
4) Third Treatment Phase (Refractory)
Status Epilepticus treatment:
1) Stabilization Phase (0-5 minutes)
what should take place here?
- here emergency treatment should be done as soon as possible beginning in the stabilization phase.
- during this time, keep track of how long the patient has been seizing. (TIME THE SEIZURE)
- MONITOR THE PATIENTS VITALS (drug levels for AEDs, electrolytes, glucose)
- Assess patients oxygen levels & start ECG readings at this time.
- look for any reversible causes of seizures, like low blood sugars. (treat with D25 - D50)
-IV access should also be attempted at this phase so labs can be drawn
- No need to wait for labs to begin treatment, this can contribute to patient harm
Status Epilepticus treatment:
2) Initial Treatment Phase (5-20 minutes):
what should take place here?
- ## drug should be given within the first 20 minutes of receiving the patient for care.
- these are all preferred drugs because they all have a very fast onset of action!
Options:
IV lorazepam (Ativan)
IM midazolam (Versed)
IV diazepam - these drugs slow neuronal firing very quickly
- remember it is all about optimizing our time and treating patients quickly.
Status Epilepticus treatment:
2) Initial Treatment Phase (5-20 minutes):
If NONE of the preferred options are available
IV lorazepam (Ativan)
IM midazolam (Versed)
IV diazepam
then what are the alternative we can use?
- if NONE of these preferred options are available then we can use:
— IV phenobarbital
— rectal (PR-per rectum) diazepam (Diastat Acudial)
— intranasal or buccal midazolam.
Status Epilepticus treatment:
3) Second Treatment Phase (20-40 minutes):
what should take place here?
- ## if seizures continue after the initial treatment phase, then we move into the Second Phase of Treatment.
- for this phase we give IV Antiseizure medications
Possible Options include:
- IV fosphenytoin
- IV valproic acid
- IV levetiracetam
- IV phenobarbital
Status Epilepticus treatment:
3) Second Treatment Phase (20-40 minutes):
But, what do you do when none of this works and the patient continues to have seizures?
If seizure persists despite giving an injectable benzodiazepine AND IV antiseizure medication
Then Third Treatment Phase (Refractory):
- there is No clear evidence to guide therapy
- best option would be to repeat second line therapy or give midazolam, pentobarbital, or propofol with continuous EEG monitoring.
Dispensing Requirements for pharmacists:
Diastat Acudial:
dispensing steps include:
1)
2)
3)
4)
- a rectal diazepam gel used to stop an active seizure.
- it is commonly used as an adjunctive treatment in patients with refractory epilepsy, who experience random episodes of increased seizure activity.
- a caregiver usually administers it outside of a healthcare setting and sometimes may be given in a longer health care facility.
- Each Kit comes with 2 prefilled rectal syringes
- Pharmacist MUST dial AND lock correct prescribed dose before dispensing to a patient or caregiver. - ## syringes come in 2.5, 10, and 20mg
1) Hold the barrel of syringe in one hand with cap facing downward and dose window visible.
2) To dial the dose- Twist cap to adjust dose being careful not to remove it. Confirm correct dose is visible in dosing window.
3) Lock dose, by grasping locking ring at bottom of syringe barrel and pushing it upwards. Green “READY” band is revealed once dose is locked.
4) Repeat steps for second syringe in kit.
- When counseling, check both syringes with the patient before they leave the pharmacy to ensure they are dialed and locked.
Chronic Seizure Management:
When it comes to chronic seizure management, what are our goals?
1)- control seizures with minimal treatment side effects
- we can help improve patients quality of life by accomplishing these 2 things.
Chronic Seizure Management: Treatment
Primary Tx:
Adjuvant Tx:
Primary Tx:
- think of the mainstay treatments for the patients with epilepsy.
- 1st line treatment for epilepsy: (AED) Antiepileptic Drugs
eg. [lamotrigine, valproate, levetiracetam]
- Do NOT stop these drugs abruptly, can precipitate a seizure to occur.
- If need to stop an agent then tamper.
- ## Cannabis-derived products, often used in patients with certain refractory seizures. Cannabidiol or (CBD- Epidiolex) was the first approved cannabis derived medication approved by the FDA to treat rare forms of epilepsy.
- ## Neurostimulation is an adjuvant nondrug treatment that can be beneficial in drug resistant epilepsy. It involves using a device that delivers electromagnetic energy to stimulate different targeted areas of the nervous system. With a goal of altering the conduction pathway to reduce seizures. Device can be implanted or can be external.
- Ketogenic diet is used to help reduce seizure frequency especially in refractory seizures. The diet contains high fats, normal proteins and low carbohydrates (usually a 4:1 ratio of fats to combined protein and carbohydrates). [This forces the body to break down fatty acids into ketone bodies as an energy source. ketone bodies pass into the brain and replace glucose. The body burning ketones for energy instead of glucose].
- The diet mimics a starvation state and induces ketogenesis- the breakdown of fatty acids into ketones, as the bodies primary energy source. This shift to ketones is thought to play a role in its anticonvulsant effect.
HIGH fat, LOW carb, with protein diet
Foods that would be encouraged in diet: “High fat foods & animal proteins.”
- eggs,
- leafy vegetables
- Pork, poultry, beef
- Nuts, seeds
- Olive oil, coconut oil
- seafood
- ## cheeseThere are modifications of the ketogenic diet that exist
ex. modified Atkins diet is a version of the ketogenic diet that allows for more flexibility in food selection.
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Foods to AVOID when following a ketogenic diet
-
- Fried Foods
- Coffee creamers
- Baked goods
- Microwavable meals “processed food products”
- Pastas
- Potatoes
Chronic Seizure Management:
Because the ketogenic diet is very restrictive.
Nutritional deficits can happen if not careful.
*Supplementation with ___________ is essential for ALL patients on a ketogenic diet.
For patients on a ketogenic diet, what is recommended for patients to take?
multivitamins
calcium
Vitamin D
*Choosing a low carbohydrate multivitamin is recommended and should include selenium. (prevent alopecia from AED like lamotrigine and valproic acid)
- some antiseizure medications can increase the risk of bone fractures, making calcium and vitamin D supplements necessary. For ALL AED, patients should supplement with calcium and vitamin D.
Antiseizure Medications Overview:
How and why certain antiseizure medications work-
There are 2 classifications for antiseizure medications:
1)
2)
1) we can classify AED based on the types of seizures they treat
2) we can classify AED by their mechanism of action
Antiseizure Medications Overview:
1) Classification of Antiseizure medications based on seizures they treat:
- Broad spectrum:
- Narrow spectrum:
Broad spectrum: antiseizure medications that treat Focal seizures and any Generalized seizures.
(e.g. lamotrigine, levetiracetam, topiramate, valproate)
-valproic acid: therapeutic range [50-100 mcg/mL (up to 150mcg/mL in some patients)] IF albumin LOW (<3.5g/dL), then calculate a corrected level using same equation for phenytoin.
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Narrow spectrum: antiseizure medications are NOT used to treat both. They primarily treat one type of seizure and that is usually Focal seizures.
(e.g. carbamazepine, phenytoin)
carbamazepine: therapeutic range [4-12 mcg/mL]
phenytoin:
therapeutic range [10-20 mcg/mL] total level, [1-2.5mcg/mL] free level;
IF albumin LOW then calculate a corrected phenytoin level.
fosphenytoin: “dosed in phenytoin equivalents (PE)”
1mg (PE) phenytoin equivalent = 1mg phenytoin
1mg (PE) phenytoin equivalent = 1.5mg fosphenytoin
- narrow spectrum agents also include a drug that treats a specific generalized seizure type called absence seizures. (e.g. ethosuximide)
There are no motor symptoms with this type of seizure.
Antiseizure Medications Overview:
“another way to classify antiseizure medications”
-
-
1- Alter ion channels or proteins (that are involved with neuronal firing or transmission of electrical activity)
2- Increase (GABA) gamma-aminobutyric acid (inhibitory neurotransmitter), so slows down neuronal firing.
3- Decrease glutamate activity (excitatory neurotransmitter)
Antiseizure Medications Overview:
Ion channels that are primarily involved in propagating neuronal signals or electrical impulses across the neuron are ________________.
Na
Ca
Cl
Antiseizure Medications Overview:
Blocking ___ channels = decreases excitatory transmission (glutamate).
Na
- anything that decreases glutamate activity decreases seizure activity.
Antiseizure Medications Overview:
Increasing GABA activity, promotes the activation of ___________ ion channels on the receiving neuron. This Causes an increase in inhibitory neurotransmission. Resulting in decreased seizure activity.
Activating ________ channels = leads to increasing inhibitory transmission (GABA).
Cl
Cl chloride
Antiseizure Medications Overview:
Major Mechanisms of Common Antiseizure Medications-
- Benzodiazepines
- Phenobarbital
both work on-
- enhancing GABA effects
Antiseizure Medications Overview:
Major Mechanisms of Common Antiseizure Medications-
- Valproate
is believed to work by blocking Na channels and increasing GABA concentrations within the brain.
Antiseizure Medications Overview:
Major Mechanisms of Common Antiseizure Medications-
- Levetiracetam
?
*Inhibits vesicle fusion by binding to SV2A proteins. this is thought to interfere with neurotransmitter transport.
- Ca channel blocker and increases GABA- - -???
Antiseizure Medications Overview:
Major Mechanisms of Common Antiseizure Medications-
- carbamazepine
- phenytoin/fosphenytoin
- topiramate
work by primarily blocking Na channels.
remember- blocking those sodium channels, blocks the effects of glutamate.
Antiseizure Medications Overview:
Major Mechanisms of Common Antiseizure Medications-
ethosuximide
blocks T-type Ca channels
Antiseizure Medications Overview:
Major Mechanisms of Common Antiseizure Medications-
- Lamotrigine
- blocks Na channels and decreases glutamate concentrations.
Antiseizure Medications Overview:
Major Mechanisms of action in Common Antiseizure Medications-
1) Increase GABA (inhibitory neurotransmitter)
2) Decrease Glutamate (excitatory neurotransmitter)
3) Ca channel blockers
4) Na channel blockers
Common Adverse Effects of antiseizure medications:
- although there are many different antiseizure medications, they have a few adverse effects that are similar between them.
This is related to how they work:
What are the 4 common adverse effects across all types of seizure medications:
-1
-2
-3
-4
since seizures result from uncontrolled neuronal firing. Antiseizure medications decreasing neuronal activity through CNS depression is beneficial in stopping seizures. However, there are unwanted effects.
1) CNS depression: confusion, sedation, poor coordination, falls (increased risk), impaired cognition.
- - - patients starting antiseizure medications should be warned that these medications may also impair there focus or reaction time.
2) Suicide risk: can increase risk of suicidal thoughts or behaviors.
– both patients and caregivers should be advised to Monitor changes in mood or behavior when starting an antiseizure medication.
– something to be mindful of especially in patients with psychiatric conditions like depression.
3) Bone loss: increased risk of fractures.
- antiseizure medications can reduce bone mineral density, alter vitamin D metabolism, and affect bone remodeling. Although this can happen with almost all antiseizure medications, enzyme inducing antiseizure medications ARE the MOST common culprit for this adverse effect. The enzyme induction causes increased vitamin D metabolism to inactive metabolites. Leading to less active vitamin D available and decreased gut absorption of calcium.
- patients on antiseizure medications are at an increased risk for fractures due to bone loss.
- Calcium AND Vitamin D supplementation is recommendedfor all patients on antiseizure medications to reduce the risk of fractures.
4) Rash: benign or life-threatening (eg SJS, TEN, DRESS) [Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis, Drug Reaction with eosinophilia and Systemic Symptoms].
- antiseizure medications can cause a rash. They range from benign to life threatening.
- the risk of rash is dose dependent. Typically develops early on in treatment, but can happen anytime during treatment.
- the risk of rash can be further increased with dose escalation or with certain combinations of antiseizure medications.
DRESS is another hypersensitivity reaction that has cutaneous manifestations.
Lamictal
Lamictal ODT
Lamictal XR
Chewable tablet
Class:
Indications:
Seizure Coverage:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
lamotrigine
Class: antiepileptic
Indications: seizures
- also used in bipolar disorder
Seizure Coverage: Broad spectrum coverage
MOA: blocks Na channels and decreases glutamate concentrations
Dosage forms:
*Dosing: [Titrating medication very important to prevent serious skin reactions].
- *(initial dosing can vary based on interacting drugs)
Initial: 25mg daily for Week 1 and Week 2
Titrate: 50mg daily for Week 3 and Week 4
Weeks 5 and on: Can increase daily dose by 50mg every 1-2 weeks.
Maintenance Dose: 300-400mg daily, divide BID unless using XR (daily).
Boxed Warnings:
- Serious skin reactions, including: (Stevens-Johnson syndrome/toxic epidermal necrolysis. [These are life threatening conditions]. The rate of rash is greater in pediatrics than adults. Rash is spread across whole body with painful skin sloughing and lesions.
There is increased risk with:
- higher dosing than recommended starting doses
- dose escalation
- when used with valproate
Contraindications:
Warnings:
- risk of aseptic meningitis, blood dyscrasias, cardiac rhythm abnormalities, multiorgan hypersensitivity (DRESS) reactions, [Drug Reaction with Eosinophilia Systemic Symptoms]
*Side Effects:
- rash,
- *Alopecia “hair loss”- if this occurs, (supplement with selenium, biotin, and zinc)- to help reduce this side effect.
- N/V, ataxia (lack of balance/coordination), tremor, insomnia, blurred vision,
*Monitoring:
- rash, fever
- **general monitoring of seizure frequency, CNS depression, depressed mood and suicidality.
Pearls/Notes:
Safety Considerations:
**- advise patient or caregiver when starting the medication if any rash develops to contact medical care provider as soon as possible.
**- if patient develops a rash or signs and symptoms of hypersensitivity, then patient should stop taking medication and seek immediate medical attention.
- Always use a starter kit when initiating treatment.
- **If discontinued for greater or equal to 5 half-lives (~6 days), restart initial dosing titration. Use a starter kit.
Drug-Drug/Food interactions:
Lamictal Starter Kit [orange]
Class:
Indications:
Seizure Coverage:
MOA:
Dosage forms:
Dosing:
When would we use this starter kit?
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
lamotrigine Orange Starter Kit
[Standard starting dose kit]
Class:
Indications:
Seizure Coverage:
MOA:
Dosage forms:
Dosing:
[Orange Kit contents and dosing schedule]
Week 1: 25mg daily
Week 2: 25mg daily
Week 3: 50mg daily (two 25mg tablets)
Week 4: 50mg daily (two 25mg tablets)
Week 5: 100mg daily (1 tablet)
[42 tablets of 25mg & 7 tablets of 100mg]
-** then can continue to increase daily dose by 50mg every 1-2 weeks**
When would we use this starter kit?
-** patient has NO interacting medications**
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
