Anticonvulsants: Introduction Flashcards
At least __% of the population will have at least one seizure in their lifetime
10 percent
define seizure
Seizure: sudden change in behavior due to electrical hypersynchronization of neuronal networks in the cerebral cortex
During seizures, abnormal electrical activity can result in what 4 things?
o LOC- sometimes but not always
o Abnormal movements- people twitching around
o Atypical or odd behavior- people won’t remember what happened during the time before usually and during.
o Distorted perceptions- patients should not be able to remember what happened and timeline, if they do it is a red flag.
Site of origin determines the symptoms that are produced, for example motor cortex- what are the symptoms?
abnormal movements or generalized convulsion
Site of origin determines the symptoms that are produced, for exampleo Parietal or occipital lobe- what are the symptoms?
visual, auditory, or olfactory hallucinations
More perceptual defect than movement
epilepsy criteria
At least two unprovoked seizures occurring more than 24 hours apart
One unprovoked seizure and a probability of further seizures over the next 10 years
o Diagnosis of an epilepsy syndrome
Epilepsy Triggers- - Changes in physiologic factors such as?
o Blood gas
o pH
o Electrolytes
o Blood glucose
Epilepsy Triggers- - Changes in environmental factors such as?
o Sleep deprivation- has to be pretty significant sleep deprivation, massive amounts.
o EtOH intake or sudden withdrawal
o Stress
what are some Epilepsy Triggers other than environmental and physiologic factors?
o Trauma
o Neoplasms- brain tumor
o Genetic abnormality
o Post-stroke
We can control about what percent of epilepsy patients?
70-80%
About what percent of patients will require multiple medications
10-15%
T/F the vast majority of epilepsy patients need monotherapy
true
About what percent of patients will never achieve complete control
10%
About half of patients with new diagnosis will become seizure free with first ___
AED
with AEDs, Tolerability of ADRs is as important as _____
efficacy
AED Selection Factors
- Drug effectiveness for seizure type(s)
- Potential ADRs
- DDIs
- Comorbid medical conditions (especially hepatic and renal disease)
- Age and gender (including childbearing plans)
- Lifestyle and patient preferences
- Cost
Is AED therapy recommended after a single seizure
Immediate AED therapy is usually not necessary after single seizure
when should you generally start AED therapy?
o In those at significant risk for recurrent seizures
o After two or more unprovoked seizures
All pts started on AED should be screened for which prior to initiation?
- Hepatic failure
- Renal failure
- Depression/suicidal ideation
- Osteoporosis
Depression/suicidal ideation
which is most important if a pt fails the first trial of AED monotherapy?
- Use 2 drug monotherapy
- Start second agent while tapering off failed agent
- Immediately stop failed agent and start new one.
- Start second agent while tapering off failed agent
T/F all pts who experience a seizure should be treated with AED therapy?
FALSE
What is distinguishing characteristic of cutaneous reaction?
involvement of mucous membrane
what is mechanism of reduced efficacy of OC when taking AEDs
metabolic enzyme induction by AED
what is the most appropriate taper schedule when stopping AED therapy
6-8 months
_______ with first AED may result from breakthrough seizures (lack of efficacy) or drug intolerance
Treatment failure
after Initial AED Failure, Factors to consider for second agent is like that of initial therapy but may need to consider different___.
MOA
when switching AED medications (Except in cases of severe ADR) the second medication is typically______ to therapeutic levels while tapering off initial AED
increased
when switching AED medications, The second agent is tapered up slowly to _______.
effect or to ADR/toxicity
when switching AED medications, Need to counsel patient on likely increase in___ during the overlap period but that they will likely decrease once first AED is tapered off
ADRs
ADRs Common to AEDs
- Increased risk of suicide
- SJS, TEN, and drug rash with eosinophilia and systemic symptoms (DRESS) are rare but serious idiosyncratic reactions
- Neurocognitive impact
- Reduced vitamin levels of folate and B12
- Bone loss
- Lower gestational age, lower birth weight, smaller head circumference
- Cognitive and developmental abnormalities of exposed children later in life
- Teratogenicity
- Weight changes
- Nausea/vomiting
- Sedation
- Ataxia
- Hyponatremia
which AED drugs tend to cause worse teratogenicity
valproate, phenytoin, carbamazepine, phenobarbital, and topiramate
Increased risk of suicide is a common ADR for AEDs, what do you need to do for patients on these drugs?
need to screen for depressions and monitor it.
patients with which alleles are more common to get SJS, TEN, and drug rash with eosinophilia and systemic symptoms (DRESS) when taking certain AEDs?
**Higher risk with HLA-B1502 or HLA-A*3101 alleles
if you are worried about a patient getting SJS, TEN, and drug rash with eosinophilia and systemic symptoms (DRESS), what is a red flag to look out for?
Fever, mucocutaneous lesions –> if it is on mouth, conjunctiva, any mucosa- RED FLAG
An ADR for AEDs is Reduced vitamin levels of folate and B12, which pt population do you need to be concerned with this for?
Very important in patients who can become pregnant or are pregnant
An ADR for AEDs is Reduced vitamin levels of folate and B12, what folate dose can you supplement with?
.4 mg or 400 mcg
Many AEDs increase risk for osteoporosis so you need to monitor bone density regularly, how can you do this?
DXA scan
AEDs can have bone loss as an ADR, what dosage of calcium and/or vitamin D can you give your patients?
CA 600 BID
Vit D 800 IU per day
AEDs can cause teratogenicity, Common abnormalities are what? (5)
Neural tube folate important for this Congenital heart and urinary tract defects Skeletal abnormalities Cleft palate Face and finger dysmorphisms
_____ should be routinely prescribed to all women of childbearing age taking AEDs (i.e., prior to becoming pregnant)
Folate
when women become pregnant, Typically the AED that controls seizures should be continued. except for which AED?
valproate
If a pregnant patient must take valproate or carbamazepine, what should the folate dose be?
and when is it best to start this folate supplementation?
folate dose should be 4 mg/d
best to start folate at least three months prior to conception
hormone contraceptive Failure while taking AEDs is due to _____ induction of metabolism
hepatic enzyme
if a patient is taking AEDs, what kind of hormonal contraceptive would be good options?
o Copper or levonorgestrel IUDs are highly effective
o Hormone levels with intrauterine hormone-releasing systems (Mirena) or depot injections of progesterone are not affected
if you have to take an estrogen hormonal contraceptive while taking an AED, what should you do to the OC dose?
- If must use OC, consider increasing dose to minimum of 50 mcg of estrogen component and/or use extended cycle regimens but realize that this may increase seizures
- Efficacy of emergency contraception (Plan B) may be affected just as OC
in regards to patients with seizures and driving, what to most stated require before allowing them to drive again?
Most require patients be free of seizures for some specified time period and submit a clinician’s evaluation regarding ability to drive safely
how long should you wait before considering a trial of AED?
Should wait at least 2 to 4 years before considering a trial off AED
Patient must be seizure-free for that time
when discontinuing an AED, how should you stop the drug?
Dose should be tapered very slowly (i.e., months)
Reason to Consider Discontinuation of AED Therapy
- Offers pt a sense of being “cured” v. chronic mediation confers permanent “disability”
- No drug is entirely benign and ADRs associated with chronic therapy may take years to manifest
- Cognitive and behavioral ADRs may be subtle and not fully recognized until drugs are stopped
- Cost
- Special circumstances such as pregnancy or comorbid condition where outcomes may be improved and management simplified in absence of AED therapy
what things may predict a higher chance of seizure recurrence in patients that want to stop their AED medication?
o Epilepsy duration before remission (longer duration associated with higher risk)
o Seizure-free interval before antiseizure drug withdrawal (shorter interval associated with higher risk)
o Age at onset of epilepsy (onset in adulthood associated with higher risk)- the younger you are you have your first seizure, the lower the risk of recurrence.
o History of febrile seizures
o Number of seizures before remission (≥10 associated with higher risk)
o Absence of a self-limiting epilepsy syndrome (e.g., absence epilepsy, benign epilepsy with centrotemporal spikes)
o Epileptiform abnormality on EEG before withdrawal
if a well-controlled patient suddenly has breakthrough seizure or toxicity, what do you need to consider might be the cause?
Generic Substitution by pharmacy
This requires you to counsel your patients on this matter!!!
Immediate AED therapy is usually not needed for single seizure. it is Reserved for ______.
2+ seizures or if at high risk for recurrence
things to base AED choice on (7)
o Seizure type o ADR profile o DDI o Comorbid conditions o Age/gender (childbearing plans) o Lifestyle and patient preferences o Cost
If first AED is unsuccessful, try another as _______
monotherapy
Regular office visits are suggested to improve compliance, what things should you discuss with your patient?
o Pt education o ADR review o Compliance questioning o +/- drug levels o Seizure calendar review
since there is an increase risk of suicide ideation in patients taking AEDs, what three things do you need to look out for?
o Mood changes
o Depression
o Anxiety
