13 - Seizure Disorders Flashcards
Define a seizure
- occurs due to abnormal excessive and/or synchronous neuronal activity in the brain
- abnormal, paroxysmal, excessive firing of CNS neurons - transient event (doesn’t last)
Define epilepsy
chronic condition characterized by recurrent seizures which are not provoked by systemic or acute neurologic insults - enduring predisposition for seizures
Define status epilepticus
seizure lasting > 30 minutes or >2 sequential seizures without return to normal mental baseline
What is the diagnostic criteria for epilepsy?
Epilepsy is defined as when any of the following exist:
- At least 2 unprovoked (or reflex) seizures occurring more than 24 hours apart.
- One unprovoked or reflex seizure and a probability of further seizures similar to the general recurrence risk after 2 unprovoked seizures occurring over the next 10 years. This may be the case with remote structural lesions such as stroke or certain types of traumatic brain injury.
How can we treat epilepsy ?
Antiepileptic drugs, diet, surgery/VNS
60% of new patients with epilepsy are ______ or ______
young or elderly
What is the first step when a patient presents with their first seizure?
Need to rule out other physiologic (and possibly treatable) causes before beginning therapy for seizure disorder or epilepsy
What are the two branches of seizure types? Describe them.
1) Focal - small area of brain or can involve up to 1 whole hemisphere
2) Generalized - both hemispheres involved
What are types of generalized seizures? Describe them
Absence: “spaced out”
Tonic: Stiff or flexed (fall backward)
Clonic: Convulsions
Atonic: Relaxed (fall forward)
Myoclonic: Short muscle twitches
Tonic-clonic: Tonic and clonic phase (Stiff and convulsions)
_______ = GABA; binds to post -synaptic GABAa receptor to open Cl- ion channels and allow influx (makes it less likely to fire)
inhibitory
_______ = Glu binds to glutamate receptor (NMDA or non-NMDA type); net result is excitatory postsynaptic potential (makes it ready to fire)
excitatory
In seizure disorders, there is more _______ and less _______
more excitation and less inhibition
Goals of therapy for seizures
1) Eliminate seizures (reduce seizure frequency and severity)
2) Minimize SE
3) Optimize quality of life
- Address comorbid anxiety, depression
- Driving, economic security, relationships/family planning, safety, social isolation, stigma
General Principles for Treatment:
-Verify ______ of epilepsy and determine ______ if possible
Verify diagnosis of epilepsy and determine ethology if possible
General Principles for Treatment:
Match choice of AED to ____ ____
seizure type
General Principles for Treatment:
Use _____ if possible, _________ if necessary.
Use monotherapy if possible, polytherapy if necessary
General Principles for Treatment:
Consider changing the _____ of dosing to reduce toxicity
timing
When is treatment indicated?
Generally, once a patient meets the criteria for diagnosis of epilepsy (either > 2 unprovoked seizures > 24 hours apart or one seizure with risk factors that increase risk of recurrence), treatment is indicated!
Focal Seizure Type:
What 3 drugs are in both guidelines?
- Carbamazepine
- Levetiracetam
- VPA
Generalized tonic-clonic (adult) Type:
What 4 drugs are in both guidelines?
- Carbamazepine
- Lamotrigine
- VPA
- Oxcarbazepine
Absence (children):
What 2 drugs are in both guidelines?
- Ethosuximide
- VPA
What are common side effects for all AEDs (anti-epileptic drugs) ?
CNS:
- drowsiness, sedation, fatigue
- incoordination
- dizziness
- cognitive impairment (mental dulling, memory, concentration)
- diplopia (double vision)
GI side effects
Toxicities are additive (i.e. worsen with each additional AED added)
Are dose-related side effects reversible?
yes - upon lowering or d/c AED
What are some neurologic dose related SE’s ?
Neurologic:
- drowsiness, sedation
- impaired cognition
- mood changes
- irritability hyperactivity
- insomnia
- dizziness, vertigo
- ataxia
- headache
- sensory neuropathy
What are some systemic dose related SE’s?
Systemic:
- GI
- Benign elevation of liver enzymes
- Benign leukopenia
- Gingival hyperplasia
- Weight gain
- Anorexia
- Hair loss
- Hirsutism
Describe idiosyncratic reactions
- More serious and potentially life threatening
- Not dose-related
- No lab test/level identifies risk for idiosyncratic reaction
What are some risk factors for idiosyncratic reactions?
Hx of previous drug reactions, liver/kidney function, conditions affecting hematopoiesis, metabolic disorders
HLA-B* 1502 gene can cause ??
carbamazepine-induced SJS
What are the 2 MOA of idiosyncratic reactions?
1) Immune-mediated reaction to the drug
2) Genetics - unusual sensitivity to the drug
What are hypersensitivity reactions? And give examples
- Stevens-Johnson syndrome (SJS)
- Toxic Epidermal Necrosis (TEN)
- Drug rash with eosinophilia and systemic symptoms (DRESS)
Characterized by fever & rash
List some other idiosyncratic reactions?
- Agranulocytosis
- Aplastic anemia
- Thrombocytopenia
- Hepatotoxicity
- Pancreatitis
- Connective tissue disorder
What do we NEVER EVER EVER give to women of childbearing age? Why?
Valproic acid!!
- Greater risk of malformation and possible neurodevelopment impairment with VPA
- Avoid in pregnancy and in women of childbearing age
What 2 things cause greater risk of malformation and possible neurodevelopment impairment ?
1) Valproic acid
2) Polytherapy (particularly with VPA)
All females on AED should receive _____ _____ before any possibility of pregnancy
folic acid
Give examples of CYP P450 inducers
carbamazepine, phenytoin, phenobarbital
Give examples of CYP P450 inhibitors
valproate
When should serum level monitoring be done?
Only be done if clinically indicated:
- To assess non-adherence
- Suspected toxicity
- Adjustment of phenytoin dose
- Management of PK interactions (ex. change in bioavailability, elimination, co-medication with interacting drugs)
- Special clinical conditions: status epilepticus, organ failure, pregnant while on LMT or PHT (levels affected by pregnancy)
______ follows michaelis mention kinetics
phenytoin
How can we manage adverse effects?
1) Dose escalation rate
2) Habituation period (time to allow adverse effects to occur - varies between patients)
3) Blood levels (rate of increase, peaks)
4) Timing of doses (single vs spread our vs ER formulation)
5) PK interactions (drug interactions - change in metabolism)
6) PD interactions (additive or synergistic adverse effects)
SE management:
For new AEDs, test dose at _____
bedtime
- if side effects, delay next dose
- if side effects recur, reduce dose
- increase dose as tolerated
SE management:
Administer with food to ____ the rate of absorption
slow
When should a patient expect to see results in seizure frequency and severity?
Improvement: 1-2 weeks
Significant benefit: 1 month
*after at max dose
How are we titrating AED’s?
for most every 1-2 weeks
When should a pharmacist follow up with a patient after starting AED?
at 1 week and then every 3 days for dose changes
What needs to be tested and when?
CBC, LFT, electrolytes
@ Baseline and q3-6 months initially
When can someone d/c seizure meds? How should it be done?
Up to the patient when they have had a seizure-free period of > 2 years implies overall >60% chance of successful withdrawal in some epilepsy syndromes
Favorable factors:
- Control achieved easily on one drug at low dose
- No previous unsuccessful attempts at withdrawal
- Normal neurologic exam at EEG
Consider relative risk/benefit
- To be done SLOWLY
- At least 2-3 months (up to 6+ months for benzos and barbiturates)
- One drug at a time
Why is status epilepticus a neurologic emergency ?
- Associated with brain damage, tx resistance, and death
- Poorer outcomes increase with increased seizure duration
When is immediate care of status epileptics required?
1) Seizure lasting > 5 minutes
2) Repeated convulsive seizures (>3 in one hour)
What is supportive treatment for status epilepticus ?
- patient stabilization
- adequate oxygenation
- preservation of cardiorespiratory function
- management of systemic complications
- aggressive assessment of underlying causes
What are abortive treatments for status epilepticus ? ABORTION FOR SEIZURES NOT BABIES
1) Benzo (lorazepam, diazepam) - buccal midazolam if IV not available
- 1st line for active seizures including status epilepticus
- Effective in terminating seizures in 75-90% of patients
2) Anticonvulsant (phenobarb, phenytoin)
- 2nd line if benzodiazepine does not terminate seizure
A ______ diet may be beneficial
ketogenic
What antiepileptic drugs help with the following patient characteristic:
Depression
Lamotrigine, oxcarbazepine
mood stabilizing effects
What antiepileptic drugs help with the following patient characteristic:
Migraine
Topiramate, valproate
What antiepileptic drugs help with the following patient characteristics:
Chronic pain
Pregabalin, gabapentin, oxcarbazepine, carbamazepine, lacosamide
(specifically, neuropathic pain)
What antiepileptic drugs help with the following patient characteristics:
Obesity
Topiramate, zonisamide
What antiepileptic drugs help with the following patient characteristics:
Women of childbearing potential
avoid VPA
What antiepileptic drugs help with the following patient characteristics:
Older adults
Lamotrigine, gabapentin, topiramate
What antiepileptic drugs help with the following patient characteristics:
Asian
Avoid carbamazepine (HLA-B 1502 allele = risk of hypersensitivity reactions)
What antiepileptic drugs help with the following patient characteristics:
Nephrolithiasis
Avoid topiramate and zonisamide
If benefit > risk, suggest increased water intake
What antiepileptic drugs help with the following patient characteristics:
Atopic (rash prone)
Avoid Lamotrigine and carbamazepine
Which drugs decrease concentration of birth control ?
- phenobarb
- phenytoin
- carbamazepine
- topiramate
- oxcarbazepine
What drug does estrogen decrease the concentration of ?
lamotrigdine
What are some important lifestyle things that you want to know about a patient who has seizures ?
- do they drive?
- alcohol
- recreational drug use
- sleep habits
- caffeine
- insurance ?
How do we manage AED and OCP interactions?
- Ideally, select an alternative, non-interacting agent or alternative contraceptive method (ex. Depo Provera, Mirena)
- If possible, use OCP continuously (no placebo break) = continuous suppression of gonadotropin secretion and ovarian function
- Use OCP with progestin component high enough to suppress ovulation (as estrogen is the hormone most effected by AED use)
- Or use “high dose” estrogens (> 50 mpg)
What are some potential seizure triggers?
- missed medication
- stress/anxiety
- missed sleep
- hormonal changes
- acute illness
- alcohol/drug use
- drug interactions
- overexertion
- poor diet/missed meals
For the exam:
Know the TABLE (for each categories pick 2-3 drugs and know them really well)
okay man
