Epilepsy Flashcards
When choosing an antiepileptic drug, _________________ should first be considered
the presenting epilepsy syndrome
If the syndrome is not clear, the seizure type should determine the choice of treatment
What secondary factors contribute to the choice of anti-epileptic medication? (4)
- Concomitant medication
- Co-morbidity
- Age
- Sex
How is dosage frequency determined when treating epilepsy?
Often determined by plasma-drug half-life and should be kept as low as possible to encourage adherence with the drug regimen
Most antiepileptics, when used in the usual dosage, can be given _______ daily
twice
Which antiepileptics can be given once daily? (4)
- Lamotrigine
- Perampanel
- Phenobarbital
- Phenytoin
All have longer half-lives so once daily at bedtime is recommended
Why are large doses of antiepileptics given more frequently (divided doses)?
To avoid adverse effects associated with high peak plasma-drug concentration
When monotherapy with a first-line AED has failed, what should be tried?
Monotherapy with a second drug
What should be done before starting an alternative drug if the first drug showed lack of efficacy?
Check diagnosis
When changing from one AED to another, what should be kept in mind?
The change from one antiepileptic drug to another should be cautious, slowly withdrawing the first drug only when the new regimen has been established
What must be considered when prescribing combination therapy with multiple AEDs?
A single antiepileptic drug should be prescribed wherever possible.
Combination therapy with two or more antiepileptic drugs may be necessary, but the concurrent use of antiepileptic drugs increases the risk of adverse effects and drug interactions.
If combination therapy does not bring about worthwhile benefits, revert to the regimen (monotherapy or combination therapy) that provided the best balance between tolerability and efficacy.
Pharmacological management for epilepsy focuses on striking a balance between _________ and __________
Tolerability
efficacy
Thus, if combination therapy does not bring about worthwhile benefits, revert to the regimen (monotherapy or combination therapy) that provided the best balance between tolerability and efficacy. A single antiepileptic drug should be prescribed wherever possible.
A Europe-wide review concluded that ALL antiepileptic drugs may be associated with a small increased risk of _______________
suicidal thoughts and behavior
The MHRA has recommended that patients and their carers should be advised to seek medical advice if any mood changes, distressing thoughts, or feelings about suicide or self-harming develop, and that the patient should be referred for appropriate treatment if necessary
When do suicidal thoughts and behavior typically arise after initiating AED therapy?
May occur as early as 1 week after initiation of treatment
What advice should patients be given if they develop suicidal thoughts or behavior after initiating AED therapy? (2)
- Do NOT stop or switch AED treatment
2. Seek advice from a healthcare professional
For which AEDs are doctors advised to ensure that their patient is maintained on a specific manufacturer’s product (as opposed to switching to a generic) when treating epilepsy? (4)
- Carbamazepine
- Phenobarbital
- Phenytoin
- Primidone
For which drugs is it usually unnecessary to ensure that patients are maintained on a specific manufacturer’s AED for the treatment of epilepsy? (8)
- Brivaracetam
- Ethozuximide
- Gabapentin
- Lacosamide
- Levetiracetam
- Pregabalin
- Tiagabine
- Vigabatrin
In these cases, a generic will do; differences between alternative products (eg product name, packaging, appearance and taste) should not affect drug efficacy UNLESS it leads to patient dissatisfaction, dosing errors, and/or reduced adherence
What are the non-clinical factors that may affect the decision to switch a patient from a name-brand AED to a generic for the treatment of epilepsy? (6)
Differences between alternative products (e.g. product name, packaging, appearance, and taste) may be perceived negatively by patients and/or carers, and may lead to…
- Dissatisfaction
- Anxiety
- Confusion
- Dosing errors
- Reduced adherence
- Difficulties for patients with co-morbid autism, mental health problems, or learning disability
For which AEDs should the need for continued supply of a particular name-brand product be based on clinical judgement and consultation with the patient and/or carer? (10)
- Clobazam
- Clonazepam
- Eslicarbazepine acetate
- Lamotrigine
- Oxcarbazepine
- Perampanel
- Rufinamide
- Topiramate
- Valproate
- Zonisamide
Should take into account factors such as seizure frequency, treatment history, potential implications to the patient of having a breakthrough seizure
Why is there concern regarding switching AEDs in patients previously stabilized on a branded product to a generic?
Due to concerns regarding loss of seizure control and/or worsening of side-effects around the time of the switch
A study conducted by the CHM concluded that the reported effects could have been due to chance association but a causal role could not be ruled out in all cases
Different antiepileptic drugs vary considerably in their characteristics, which influences the risk of whether switching between different manufacturers’ products of a particular drug may cause ___________ or _____________
adverse effects
loss of seizure control
What is antiepileptic hypersensitivity syndrome?
A rare but potentially fatal syndrome associated with some AEDs (carbamazepine, lacosamide, lamotrigine, oxcarbazepine, phenobarbital, phenytoin, primidone, and rufinamide)
Symptoms usually start 1-8 weeks from onset of exposure and include:
- fever
- rash
- lymphadenopathy
- liver dysfunction
- hematological abnormalities
- renal abnormalities
- pulmonary abnormalities
- vasculitis
- multi-organ failure
Which drugs are known to cause antiepileptic hypersensitivity syndrome? (8)
- Carbamazepine
- Lacosamide
- Lamotrigine
- Oxcarbazepine
- Phenobarbital
- Phenytoin
- Primidone
- Rufinamide
When do symptoms of antiepileptic hypersensitivity syndrome usually appear?
Between 1-8 weeks after initiation of therapy
Interactions between antiepileptics are complex and may increase toxicity (with/without) a corresponding increase in antiepileptic effect. Interactions are usually caused by _______________
Without
hepatic enzyme induction or inhibition
Avoid abrupt withdrawal of AEDs, particularly of barbiturates and benzodiazepines, because this can precipitate __________________
severe rebound seizures
Which AEDs are strongly associated with severe rebound seizures upon abrupt withdrawal? (2)
- Benzodiazepines
- Barbiturates
Reduction in dosage should be gradual and, in the case of barbiturates, withdrawal of the drug may take months.
True or false: AEDs may be gradually withdrawn in patients who have been seizure-free for 12 months or more
False
The decision to withdraw antiepileptic drugs from a seizure-free patient, and its timing, is often difficult and depends on individual circumstances. Even in patients who have been seizure-free for several years, there is a significant risk of seizure recurrence on drug withdrawal.
How should drugs be withdrawn in patients who are taking several AEDs?
One at a time
If a driver has a seizure (of any type), how does this affect their license?
they must stop driving immediately and inform the Driver and Vehicle Licensing Agency (DVLA)
Patients who have had a first unprovoked epileptic seizure or a single isolated seizure must not drive for ____________
6 months
driving may then be resumed, provided the patient has been assessed by a specialist as fit to drive and investigations do NOT suggest a risk of further seizures
Patients with established epilepsy may drive a motor vehicle provided they are… (4)
- Not a danger to the public
- Are compliant with treatment and follow-up
- Have been seizure-free for at least one year
- Do NOT have a history of unprovoked seizures
additional criteria apply for drivers of large goods or passenger carrying vehicles—consult DVLA guidance
Patients who have had a seizure while asleep are not permitted to drive for one year from the date of each seizure, unless… (2)
- a history or pattern of sleep seizures occurring only ever while asleep has been established over the course of at least one year from the date of the first sleep seizure
OR
- an established pattern of purely asleep seizures can be demonstrated over the course of three years if the patient has previously had seizures whilst awake (or awake and asleep)
What is the DVLA recommendation regarding AEDs? (3)
Patients should not drive…
- During medication changes
- During medication withdrawal
- 6 months after their last dose
True or false: If a seizure occurs due to a prescribed change or withdrawal of epilepsy treatment, the patient will have their driving license revoked for 1 year
True
Although relicensing may be considered earlier if treatment has been reinstated for 6 months and no further seizures have occurred.
Are AEDs safe in pregnancy?
No, associated with teratogenicity especially if used in the first trimester and particularly in patients taking two or more AEDs
Which AED is considered most teratogenic?
Valproate; approximately 10% risk of congenital malformations and 30-40% risk of neurodevelopmental disorders
___________ should not be used first line in women of childbearing potential
Valproate
Valproate must not be used during pregnancy unless there is no other suitable alternative.
Which AEDs are considered safest in pregnancy? (2)
- Lamotrigine
2. Levetiracetam
Are carbamazepine, phenobarbital, phenytoin, and topiramate safe to use in pregnancy?
Associated with an increased risk of major congenital malformations in a dose-dependent fashion
+neurodevelopmental effects associated with phenobarbital and phenytoin
+intrauterine growth restriction associated with phenobarbital, topiramate, and zonisamide
What advice should be given to women who are taking AEDs and are planning a pregnancy? (2)
- Refer to a specialist
2. Offer folic acid
What advice should be given to women taking AEDs if they suspect they could be pregnant? (2)
- Do not stop their AED treatment without discussing this with their doctor
- Seek urgent medical advice
What additional considerations should be made regarding efficacy when prescribing AEDs in pregnancy?
Plasma concentrations of AEDs (particularly lamotrigine and phenytoin) can be affected by physiological changes during pregnancy and post-partum
Prescribers should consult product literature and relevant clinical guidance for dosing and monitoring recommendations
Females of childbearing potential who take antiepileptic drugs should be given advice about the need for a _______________
highly effective contraception method to avoid unplanned pregnancy
Some antiepileptic drugs can reduce the efficacy of hormonal contraceptives, and the efficacy of some antiepileptics may be affected by hormonal contraceptives
The likelihood of a woman who is taking antiepileptic drugs having a baby with no malformations is at least ________
90%
True or false: Once an unplanned pregnancy is discovered it is usually too late for changes to be made to the treatment regimen
True
The risk of harm to the mother and fetus from convulsive seizures outweighs the risk of continued therapy
The likelihood of a woman who is taking antiepileptic drugs having a baby with no malformations is at least 90%, and it is important that female patients do not stop taking essential treatment because of concern over harm to the fetus
To reduce the risk of neural tube defects, folate supplementation is advised throughout the first trimester.
Female patients who have seizures in the second half of pregnancy should be assessed for __________ before any change is made to antiepileptic treatment
eclampsia
How is Status epilepticus managed in pregnant women?
According to the standard protocol
_________ at birth minimises the risk of neonatal haemorrhage associated with antiepileptics.
Routine injection of vitamin K
Withdrawal effects of AEDs in the newborn may occur with some antiepileptic drugs, in particular __________ and __________
benzodiazepines
phenobarbital
True or false: Women taking antiepileptic monotherapy should generally be encouraged to breast-feed
True
However, if a woman is on combination therapy or if there are other risk factors, such as premature birth, specialist advice should be sought.
All infants breastfed by women taking AEDs should be monitored for: (4)
- Sedation
- Feeding difficulties
- Adequate weight gain
- Developmental milestones
Which AEDs are known to readily enter breast milk? (4)
- Ethosuximide
- Lamotrigine
- Primidone
- Zonisamide
Serum-drug concentration monitoring should be undertaken in breast-fed infants if suspected adverse reactions develop
Is it necessary to monitor serum-drug concentrations of babies being breastfed by mothers taking AEDs?
Only if adverse reactions are suspected; if toxicity develops it may be necessary to introduce formula feeds to limit the infant’s drug exposure, or to wean the infant off breast-milk altogether.
__________, __________, and __________ are associated with an established risk of drowsiness in breast-fed babies and caution is required.
Primidone
Phenobarbital
Benzodiazepines
Withdrawal effects may occur in infants if a mother suddenly stops breast-feeding, particularly if she is taking ____________, ____________, or ____________
phenobarbital
primidone
lamotrigine
What are the first line drugs for managing focal seizures with or without secondary generalization? (2)
- Carbamazepine
- Lamotrigine
Second line:
- oxcarbazepine
- valproate
- levetiracetam
If monotherapy is unsuccessful in the treatment of focal seizures with first-line antiepileptic drugs, what should be considered?
adjunctive treatment with a second AED:
- carbamazepine
- clobazam
- gabapenitn
- lamotrigine
- levetiracetam
- oxcarbazepine
- valproate
- topiramate
*if adjunctive treatment is ineffective or not tolerated, consult a specialist
What is the first-line treatment for newly diagnosed generalized tonic-clinic seizures?
Valproate EXCEPT in female patients of childbearing potential unless they are on LARC
Second line: lamotrigine (but may exacerbate Myoclonic seizures)
What is the first line AED treatment for patients with established epilepsy with generalized tonic-clinic seizures only? (2)
- Valproate
2. Lamotrigine
What are the drugs of choice for absence seizures? (2)
- Ethosuximide
- Valproate (except in females of childbearing potential)
Second line:
- lamotrigine
What is the drug of choice for managing newly diagnosed Myoclonic seizures?
Valproate (except in females of childbearing potential)
Second line:
- topiramate
- levetiracetam
What is the drug of choice for the treatment of atonic and tonic seizures?
Valproate (except in females of childbearing potential)
*lamotrigine can be added as adjunctive treatment
What is Dravet syndrome?
A rare drug-resistant epilepsy that begins in the first year of life in an otherwise healthy infant;
It is lifelong and usually presents with a prolonged seizure with fever that affects one side of the body
Most commonly caused by a severe SCN1A gene mutation
What is Lennox-Gastaut syndrome?
A type of severe epilepsy beginning in childhood
May lead to tonic, atonic, absence, myoclonic
Commonly caused by unusual brain development, stroke, serious head injury, brain tumor, brain infection, brain hypoxia, tuberous sclerosis
What is the treatment of Dravet syndrome? (2)
- Valproate (except females of childbearing potential)
- Topiramate (unlicensed)
A tertiary specialist should be involved in decisions regarding treatment of Dravet syndrome
What is the treatment of choice in patients with Lennox-Gastaut Syndrome?
Valproate (except females of childbearing potential)
A tertiary specialist should be involved in decisions regarding treatment of Lennox-Gastaut syndrome
What are the main drugs used as anti-epileptics? (12)
- Carbamazepine (and related drugs oxcarbazepine, eslicarbazepine acetate)
- Ethosuximide
- Gabapentin and pregabalin
- Lamotrigine
- Levetiracetam and brivaracetam
- Phenobarbital and primidone
- Phenytoin
- Rufinamide
- Topiramate
- Valproate
- Zonisamide
- Benzodiazepine
Carbamazepine is the drug of choice for which types of seizures? (2)
Simple and complex focal seizures
Generalized tonic clonic seizures
___________ may exacerbate tonic, atonic, myoclonic and absence seizures and is therefore not recommended if these seizures are present
Carbamazepine
____________ is licensed as monotherapy or adjunctive therapy for the treatment of focal seizures with or without secondary generalised tonic-clonic seizures.
Oxcarbazepine
____________ is not recommended in tonic, atonic, absence or myoclonic seizures due to the risk of seizure exacerbation.
Oxcarbazepine
Also carbamazepine
What are the indications of eslicarbazepine acetate?
Licensed for adjunctive treatment in adults with focal seizures with or without secondary generalization