Epilepsy Flashcards
1
Q
What is epilepsy?
A
The tendency to have recurrent seizures
Primarily diagnosed after a person has experienced two unprovoked seizures more than 24 hours apart
2
Q
What is the practical definition of epilepsy based on the International League Against Epilepsy task force?
A
Epilepsy is a disease of the brain defined by any of the following conditions:
* At least two unprovoked (or reflex [i.e. induced by a specific trigger]) seizures occurring >24 hours apart or
* One unprovoked (or reflex) seizure and a probability of further seizures, similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next ten years, based on neurologist experience or
* Diagnosis of an epilepsy syndrome
3
Q
When is epilepsy defined as resolved?
A
In individuals with an age-dependent epilepsy syndrome, who are now past the age criteria for certain syndromes
OR
Those who are seizure free for more than 10 years, with no antiseizure medicines and have not needed antiseizure medicines for the past 5 years
* Withdrawal of medication usually considered after 2 years of seizure freedom on medication
4
Q
Can epilepsy be cured? If so, how?
A
The only cure for epilepsy is surgical removal of brain lesion, and only in suitable individuals.
Some epilepsy syndromes of childhood will resolve as the child ages. However, in other cases, the child may go on to develop a different epilepsy syndrome.
5
Q
Epilepsy is the most common serious neurological condition in the UK.
1. How many people does it affect?
2. Is it higher in males or females?
3. Is incidence higher in lower or higher income countries?
A
- 600,000
- Incidence is higher in males than females (50.7 vs. 46.2 per 100,000 people)
- Lower income
6
Q
Epilepsy is the most common at what ages?
A
- Infancy, often caused by brain damage during birth
- Older age, owing to cerebrovascular disease, with seizures common after stroke
The incidence steadily increases after 50 years old, with the greatest increase seen in those aged over 80 years.
7
Q
What is the most common cause of epilepsy?
A
For many people worldwide — perhaps as many as 50% — the cause of their epilepsy is not determined
Less common causes of epilepsy include brain tumours, head injury and/or CNS infections, such as meningitis. In developing countries, infections caused by parasites are the most common cause.
8
Q
What is the most common cause of epilepsy?
A
For many people worldwide — perhaps as many as 50% — the cause of their epilepsy is not determined
- It is possible that many epilepsies have an underlying genetic cause, although this may not necessarily be inherited but caused by spontaneous gene mutation
In developing countries, infections caused by parasites are the most common cause
9
Q
People with epilepsy have higher incidence of what diseases/conditions?
A
-
CNS-related conditions (depression, anxiety, sleep issues, migraine and memory problems)
- Suicide is up to 3.5–5.8 times greater in epileptic patients
- Up to half of all patients with epilepsy report some form of memory issue. Topiramate also associated with memory problems.
- Somatic conditions (T1DM, ischaemic heart disease, arthritis and gastric bleeds)
Prevalence of epilepsy in people with an intellectual disability (ID) is also as high as 22%
10
Q
What is forced normalisation?
A
For people with co-morbid mental health conditions, improving psychosis can result in a worsening of seizure control and, likewise, improvements in seizure control can worsen psychosis
11
Q
How is epilepsy diagnosed?
A
- Witness account of seizure
- An electroencephalogram (EEG) is carried out when a person is suspected of having epilepsy based on their clinical history (e.g. after having a seizure)
- MRI may be used to help identify any obvious lesions or scarring in the brain that are causing seizures.
*MRI recommended by NICE if: develops epilepsy before two years of age or as an adult; if focal epilepsy is suspected; or if seizures continue despite medication
12
Q
What percentage of people will be rendered seizure free after the first AED? (i.e. no seizures for at least 1 year)
What about if they need adjunctive therapy?
A
Around half
However, the probability of achieving seizure freedom reduces substantially with each subsequent drug
Around 30% of patients will require polytherapy and more than one-third of patients’ epilepsy will remain uncontrolled, which is described as refractory to medication
13
Q
Drug resistance is more likely in what situations?
A
If there is an early onset of seizures, focal seizures or multiple seizure types
14
Q
Evidence does not support any one approach over another for the management of seizures if the first drug does not control the condition or is poorly tolerated.
True or False?
A
True
There is no agreement on whether drugs with the same mechanism of action should be combined or whether drugs with differing modes of action should be selected.
15
Q
Why should dosage frequency of antiepileptic drugs be kept as low as possible?
A
To promote adherence.
16
Q
Why may large doses of antiepileptic drugs require frequent dosing?
A
To avoid adverse effects associated with high plasma-drug concentrations.
17
Q
When switching from one antiepileptic drug to another, what should be done?
A
Check diagnosis before starting alternative drug
The first drug should be slowly withdrawn only when the new regimen has been established.
18
Q
For what indication is the MHRA advice on maintaining specific products of antiepileptic drugs relative to?
A
Epilepsy
Does not apply to other indications
19
Q
The side effect profiles of many of the ASMs (including newer ASMs) are similar, regardless of the drug’s mechanism of action.
How should suspected adverse reactions to antiepileptic drugs be reported?
A
On an MHRA Yellow Card.
20
Q
When may it be necessary to dispense a product from a different manufacturer?
A
When there are supply problems, in order to maintain treatment continuity.
21
Q
What are the three risk-based categories for antiepileptic drugs?
A
Category 1: Patient should be maintained on a specific brand.
Category 2: Supply of a specific brand based on clinical judgement.
Category 3: Unnecessary to supply a specific brand.
22
Q
For which antiepileptic drugs should a patient be maintained on a specific brand? (category 1)
A
CP3
carbamazepine, phenytoin, phenobarbital, primidone
23
Q
For which antiepileptic drugs should supply of a specific brand be based upon clinical judgement? (Category 2)
A
Valproate, lamotrigine, topiramate, clobazam, zonisamide, clonazepam, perampanel, retigabine, rufinamide, oxcarbazepine, eslicarbazepine,
24
Q
For which antiepileptic drugs is it unnecessary to supply a specific brand? (Category 3)
A
Levetiracetam, lacosamide, tiagabine, gabapentin, pregabalin, ethosuximide, vigabatrin.
25
Antiepileptic drugs are associated with a small increase in risk of what psychological side effect? (MHRA alert)
Suicidal thoughts and behavior.
Symptoms may occur as early as 1 week after starting treatment
Seek medical advice and do not stop treatment.
26
If a patient on antiepileptic drugs develops suicidal thoughts and behaviors, what should they do?
Seek medical advice.
Do not stop treatment.
27
How soon since starting antiepileptic drug treatment may patients experience suicidal thoughts and behaviours?
As soon as one week after starting treatment.
28
Most antiepileptics, when used in the usual dosage, can be given twice daily.
Which antiepileptics have a long half-life which means they can be used once daily?
Lamotrigine, perampanel, phenobarbital, and phenytoin
(LP3)
29
Abrupt withdrawal of antiepileptic drugs should be avoided. How should antiepileptic drugs be withdrawn?
Withdraw under specialist supervision.
Highest risk of rebound seizures: barbiturates and benzodiazepines
Reduction in dosage should be gradual to prevent rebound seizures, usually over at least three month and longer for benzos and barbiturates
Withdraw one at a time.
Even in patients who have been seizure-free for several years, there is a significant risk of seizure recurrence on drug withdrawal.
30
How long can it take for the withdrawal of barbiturates?
Over 3 months.
31
What is the main risk with withdrawal of antiepileptic drugs?
Significant seizure recurrence.
32
Withdraw of antiepileptic drugs from a seizure-free patient may be considered after the patient has been seizure-free for how long?
At least two years
33
What vehicles can patients with epilepsy drive?
They can drive vehicles apart from large goods vehicles or passenger vehicles.
34
What conditions must be satisfied before a patient with epilepsy can drive?
If first unprovoked/single isolated seizure:
- Do not drive for 6 months
- Can drive after 6 months once assessed by specialist as fit to drive and no further risk of seizures
If established epilepsy:
- May drive if compliant with treatment and follow up
- They must be seizure free for 1 year (or have a pattern of seizures established for 1 year where there is no influence on their level of consciousness or the ability to act) **or** have established a three-year period of **only** asleep attacks if the patient previously had seizures whilst awake **or** 1 year history of sleep seizures occurring only ever while asleep
- Must have no history of unprovoked seizures
35
When does the DVLA recommend that patients with epilepsy do not drive?
Patients with epilepsy should not drive during medication changes, withdrawal of medication, or 6 months after last dose.
If a seizure occurs during withdrawal/change, license revoked for 1 year
- Can be reinstated after 6 months if treatment restarted and no seizures have occured in that period
36
Which antiepileptic drugs are associated with an increased risk of teratogenicity?
Valproate, phenytoin, primidone, phenobarbital, lamotrigine, carbamazepine.
CP3-LV
37
Which antiepileptic drug is associated with the greatest risk of congenital malformations and long-term developmental disorders?
Valproate
Carbamazepine, phenobarbital, phenytoin and topiramate also have an increased risk (the risk for carbamazepine, phenobarbital, and topiramate is dose dependent)
38
In which patients should valproate not be used unless there is no safer alternative?
People under 55 years (males or females)
Especially pregnant women, female children and women of childbearing potential.
39
How should antiseizure medicines be monitored?
* Drug-specific parameters (e.g. LFTs for sodium valpoate) are indicated before therapy and periodically in the first 6 months after starting. There is no further guidance on when they should be monitored.
* NICE recommends that FBC, U+Es, LFTs are taken for enzyme-inducing drugs every 3-5 years
* Bone metabolic tests every 2-5 years for adults taking enzyme-inducing ASMs and valproate
There is no rationale for regular plasma drug monitoring in patients taking ASMs, although there are some instances when it is indicated
There is no evidence to support a certain frequency of review in patients with epilepsy. Current NICE guidelines suggest **annual review** with a patient’s GP or epilepsy specialist
40
Considerations during medication review with patients taking ASMs?
41
List some enzyme inducing ASMs.
Carbamazepine (and analogues - eslicarbazepine, oxcarbazepine)
Perampanel (at a dose of 12 mg daily or more)
Phenobarbital
Phenytoin
Primidone
Rufinamide
Topiramate (at a dose of 200 mg daily or more)
42
What are some possible indications for ASM therapeutic drug monitoring?
* Dose optimisation of initially prescribed treatment, including patients on phenytoin therapy and in cases of suspected toxicity
* Uncontrolled seizures
* Children
* Pregnancy
* Older age
* Changes in ASM formulation, including when switching from branded to generic
* Pathological states leading to possible alterations in ASM pharmacokinetics (e.g. in hepatic or renal disease);
* Pharmacokinetic interactions (e.g. when multiple ASMs are used together).
43
What teratogenic malformation is associated with topiramate use and when is it likely to occur?
An increased risk of cleft palate when taken in the first trimester of pregnancy.
44
What advice should be given to pregnant women who also have epilepsy?
Advice about effective contraception methods to avoid unplanned pregnancies.
Women who want to become pregnant should be referred to a specialist.
Do not stop treatment abruptly.
45
What is the likelihood of a woman who is taking antiepileptic drugs having a baby with no malformations?
At least 90%. It is important not to stop taking essential treatment.
Parents should receive advice on caring for their baby to reduce seizure-associated risks. This includes avoiding bathing the baby alone and changing the baby on the floor.
46
What is the percentage of congenital malformations and neurodevelopmental disorders with **valproate**?
Congenital malformations = approx. 10% risk with valproate
(6% and 4–5% for phenytoin and carbamazepine, respectively)
Neurodevelopmental disorders = approx. 30–40% risk
47
In the case of women who are treated with sodium valproate or valproic acid, who become pregnant, what course of action is required?
An urgent consultation is required to reconsider the benefits and risks of valproate therapy.
48
When is folate supplementation advised in pregnancy? Why?
Before conception and throughout the first trimester (first 12 weeks)
5mg for patients taking antiepileptic drugs.
49
Women who have seizures during the second half of the pregnancy should be assessed for what, before changing any treatment for epilepsy?
Eclampsia.
Eclampsia is the onset of seizure in a woman with pre-eclampsia. Pre-eclampsia is a hypertensive disorder of pregnancy that presents with three main features: new onset of high blood pressure, large amounts of protein in the urine or other organ dysfunction, and oedema.
50
Routine injection of which vitamin at birth minimises the risk of neonatal hemorrhage associated with antiepileptic drugs?
Vitamin K.
51
What effects may be seen in babies born to women who have been taking antiepileptic drugs?
Withdrawal effects.
Particularly benzodiazepines and phenobarbital.
52
Can mothers on antiepileptic drugs breastfeed?
Yes if on monotherapy
If they are on combination therapy or if there are other risk factors (e.g. premature birth), seek specialist advice
53
What should babies born to mothers taking antiepileptic drugs be monitored for?
Sedation, feeding difficulties, adequate weight gain, developmental milestones, adverse effects associated with the specific antiepileptic drug.
54
If suspected adverse reactions to antiepileptic drugs occur in breastfed children, what monitoring should be carried out?
Serum-drug concentration.
55
If toxicity to an antiepileptic drug occurs in breastfed children, what course of action may be required?
The introduction of formula feeds to limit drug exposure or weaning off of breastmilk altogether.
56
What is antiepileptic hypersensitivity syndrome?
How long after exposure to a specific antiepileptic drug may patients experience the symptoms of AHS?
A rare but potentially fatal syndrome associated with some antiepileptic drugs
Results in fever, rash, lymphadenopathy, vasculitis, multiorgan failure
May present between 1 and 8 weeks after starting treatment
57
What drugs are associated with an increased risk of antiepileptic hypersensitivity syndrome?
Carbamazepine, lacosamide, lamotrigine, oxcarbazepine, phenobarbital, phenytoin, primidone, rufinamide
CP3, L2, R+O1
58
What action should be taken if signs or symptoms of antiepileptic hypersensitivity syndrome occur?
The drug should be withdrawn immediately and expert advice should be sought.
Do not re-expose.
59
What are the two main types of seizures?
Focal (70%) and generalised.
Focal seizures can become generalised.
60
Define focal seizures.
The abnormal electrical activity begins in a localised area, the ‘focus’
- Can become generalised
The type of seizure depends on where in the brain that focus is and how far from the focus the seizure activity propagates
More refractory to treatment and are more likely to go undiagnosed than generalised seizures
61
How can focal seizures be further categorized?
Focal aware/simple partial seizures and focal impaired/complex partial seizures.
62
Define focal aware/simple partial seizures.
Focal seizures where the patient remains conscious throughout the seizure.
They are able to talk, follow instructions and remember the seizure
63
For someone having a focal aware/simple partial seizure how does it present if the following are affected:
1. Temporal lobes
2. Frontal cortex
**1. Temporal lobes**
May experience an intense unpleasant sensation, such as smelling a strong smell or feeling an overwhelming sense of déjà -vu
**2. Frontal cortex**
Seizure is often movement related, so the person may display peddling or kicking movements, their head may turn to one side or they may adopt a strange bodily position
64
Define focal impaired awareness/complex partial seizures.
Focal seizures where the patient loses consciousness/is partially responsive and cannot remember what happened after the seizure has passed.
The person might be able to hear you, but not fully understand what you say or be able to respond to you. They may not react as they would normally.
65
Define generalized seizures.
Seizures where most or all of the brain is affected.
Arise simultaneously from both cerebral hemispheres of the brain, leading to an immediate loss of consciousness
66
How can generalized seizures be further categorized?
Absence seizures, myoclonic seizures, clonic seizures, atonic seizures, tonic seizures, tonic-clonic seizures.
67
Define absence seizures.
Seizures where the patient loses awareness of their surroundings, usually for up to 15 seconds.
- May appear to pause mid-sentence stare off to distance or continue walking but not be aware
- More common in children but can occur in adults
May have tens to hundreds of absence seizures a day
68
Define myoclonic seizures.
Seizures causing the patient's arms, legs or upper body to jerk or twitch, brief loss of consciousness.
Lasts fraction of a second but can happen in clusters
Often happen after waking
69
Define clonic seizures.
Similar twitching of the arms, legs or upper body as myoclonic seizures except for longer. May last for up to two minutes.
70
Define atonic seizures.
Seizures where all of the muscles suddenly relax, resulting in possible injury due to a **forwards** fall.
Lasts ~15 seconds
71
Define tonic seizures.
Seizures where all of the muscles become stiff, instant loss of consciousness resulting in possible injury from a **backwards** fall.
Lasts approx. 1 minute
72
Define tonic-clonic seizures.
Seizures with two stages and instant loss of consciousness.
First the muscles go stiff, patient may cry out or bite tongue (tonic). Then the arms and legs begin jerking and breathing may be affected (clonic). May experience incontinence.
Can last a few minutes.
73
Some people experience both focal and generalised seizures.
True or False?
True
74
Some people are diagnosed with epilepsy syndromes.
What is this? What age is it usually diagnosed?
An epilepsy syndrome is a group of signs and symptoms that tend to happen together, including particular types of seizures
Epilepsy syndromes are often diagnosed at a young age and therefore are more common in children
Patients with an epilepsy syndrome that is likely to be drug-resistant (failure of adequate trials of two antiepileptic drugs (whether as monotherapy or in combination) to achieve sustained seizure freedom) should be referred to a tertiary epilepsy service
75
Which epilepsy syndrome is seen in slightly older children (i.e. aged 12–16 years)?
Juvenile myoclonic epilepsy (JME)
Most people with JME have three seizure types: myoclonic, absences seizures and tonic-clonic seizures
(MAT)
76
What are common triggers for seizures?
* Stress and anxiety
* Poor sleep
* Prolonged periods without food
* Poor medication adherence
* Misuse of drugs, particularly stimulants (e.g. cocaine and amphetamines)
* Alcohol
77
Photosensitive epilepsy is a reflex epilepsy that occurs in response to specific afferent stimulus (photic stimulation).
How common is it? Is it more common in males or females?
2–14% of people with epilepsy
Photosensitivity is associated with genetic generalised epilepsy (also called idiopathic generalised epilepsy) and is twice as common in women
78
What is catamenial epilepsy?
A worsening of seizure control around the time of menstruation
Some women may have rescue therapy with clobazam
79
Define status epilepticus.
Any seizure lasting longer than 5 minutes or a series of seizures where the patient does not regain consciousness between seizures.
MEDICAL EMERGENCY.
80
What type of seizures should be classed as a medical emergency? (3 examples)
**1. Repeated or cluster seizures**
(typically 3 or more self-terminating seizures in 24 hours)
**2. Prolonged convulsive seizures**
(a seizure that continues for more than 2 minutes longer than the patient's usual seizure)
**3. Status epilepticus**
(a seizure that lasts 5 minutes or longer, or recurrent seizures without recovery in between)
If an individualised emergency management plan is not available, treatment with a benzodiazepine (such as rectal diazepam. clobazam or midazolam) should be urgently considered
81
What is the mechanism of action of levetiracetam?
Why is it widely used?
Its MOA differs to most ASMs — it acts by modulating synaptic neurotransmitter release by binding to the synaptic vesicle protein 2A (SV2A) in the brain.
Therefore, it can be useful as an adjunct therapy
Widely used due to its simple pharmacokinetics, lack of interactions and relatively clean safety profile. However, it's unlicensed as monotherapy.
82
Levetiracetam can have what effect on mood?
What may be an alternative drug with a similar MOA?
Increased irritability or aggression in 10–15% of patients
May require withdrawal of the drug in severe cases
Brivaracetam, which is the 4-n-propyl analogue of levetiracetam, is reported to have fewer psychiatric side effects owing to its more specific binding to SV2A, although it is not currently used widely in practice owing to a lack of experience in its use
83
What is the mechanism of action for carbamazepine?
Inhibits voltage gated sodium channels, thus preventing repetitive firing of action potentials.
No longer first line treatment due to poor tolerability
84
What is the therapeutic range of carbamazepine?
4-12 mg/L (20-50 micromol/L).
85
Should carbamazepine used for epilepsy treatment be prescribed by brand?
Yes.
e.g. Tegretol
86
What are the symptoms of carbamazepine toxicity? (iHANDBAG)
**Carbamazepine = iHandbag**
I : incoordination
H: hyponatraemia (altered personality, confusion, lethargy, reduced urine output)
A: ataxia (lack of muscle co-ordination)
N: nystagmus (involuntary eye movement)
D: drowsiness
B: blurred/ double vision
A : arrhythmias
G : GI disturances (N+V, diarrhoea)
87
What are the side effects of carbamazepine?
Hyponatraemia, blood disorders, skin disorders (SJS), hepatic disorders, oedema, movement disorders, antiepileptic hypersensitivity syndrome.
88
What blood disorders are associated with carbamazepine use?
Neutropenia and other blood disoders (Fever, sore throat, unexplained bleeding or bruising)
Treatment should be discontinued if a blood disorder develops that is severe, progressive, or accompanied by clinical manifestations (e.g. fever or sore throat), or if any evidence of significant bone marrow suppression occurs
89
What skin disorders are associated with carbamazepine use?
Mouth ulcers, rash
Rarely Stevens-Johnson syndrome (SJS) (causes rashes, blisters and peeling)
90
What are the symptoms of hepatic disorder associated with carbamazepine use?
Severe GI upset, fatigue, jaundice, dark urine.
91
What monitoring is required with carbamazepine use?
Plasma concentration (measured after 1-2 weeks to ensure within therapeutic range), FBC, renal and hepatic function.
Pre-screening for:
* HLA-B*1502 allele in individuals of Han Chinese or Thai origin (avoid unless no alternative due to increased risk of Stevens-Johnson syndrome)
* HLA-A*3101 allele in individuals of european or japanese origin
Carbamazepine (and its related drugs oxcarbazepine and eslicarbazepine) should not be routinely offered
92
How does hepatic impairment affect carbamazepine use?
Metabolism is impaired in advanced liver disease; dose reduction may be needed.
93
Increases in carbamazepine concentration may be seen when used with which drugs?
Acetazolamide, cimetidine, clarithromycin, erythromycin.
94
Decreases in carbamazepine concentration may be seen when used with which drugs?
Phenytoin, rifabutin, St. John's Wort.
95
Carbamazepine is a potent inducer of CYP450 enzyme. It reduces the plasma concentration of which drugs?
oestrogens and progestogens (can result in contraceptive pill failure), antipsychotics, corticosteroids, coumarins, eplerenone, simvastatin.
96
There is a possible increase in risk of convulsions when antiepileptics are given with which drug?
Orlistat.
97
Fosphenytoin is a prodrug form of which antiepileptic drug? How can fosphenytoin be given?
Phenytoin
Can be given via IV or IM
- IV formulation of fosphenytoin has less injection site reactions than phenytoin
- Can also be given via IM (phenytoin can only be given via IV)
- However absorption via IM too slow for status epilepticus - use IV
Doses of fosphenytoin sodium should be expressed in terms of phenytoin sodium
98
IV infusion of fosphenytoin is associated with which severe cardiovascular symptoms?
Asystole, ventricular fibrillation, cardiac arrest.
| Hypotension, bradycardia, and heart block have also been reported.
99
What steps are recommended when administering fosphenytoin via IV infusion?
Monitor HR, BP, and respiratory function during the infusion.
Observe the patient for at least 30 minutes after infusion.
If hypotension occurs, reduce the infusion rate or withdraw the drug. reduce dose or infusion rate in the elderly and in renal & hepatic impairment.
100
What safety warning comes with the use of gabapentin oral solution (Rosemont brand) in adolescents or young adults with a low body weight (39-50 kg)?
May exceed WHO recommended limits of propylene glycol, acesulfame K and saccharin.
101
What symptoms suggestive of bone marrow failure should patients and carers of patients on lamotrigine be made aware of?
Anaemia, bruising, or infection.
102
Which conditions have been rarely associated with lamotrigine use?
Aplastic anaemia, bone-marrow depression, pancytopenia, SJS
103
Which serious skin reactions have been reported in the first 8 weeks of lamotrigine use?
Stephen-Johnson's syndrome and toxic epidermal necrolysis (TEN is a more severe form of SJS).
A rare, potentially fatal disorder of the skin and mucous membranes that usually starts with flu-like symptoms, followed by a painful rash that spreads and blisters
Dose is titrated slowly to minimise risk
It can also happen if lamotrigine is stopped suddenly for a few days and then restarted at the same dose as before, without reducing the dose and then increasing it slowly again.
104
What factors increase one's risk of developing Stephen-Johnson's syndrome, toxic epidermal necrolysis, etc when taking lamotrigine?
Concomitant use of valproate (as valproate potentiates effect of lamotrigine), initial lamotrigine dosing higher than recommended, more rapid dose escalation than recommended.
105
If a patient develops a rash when taking lamotrigine, what may be the cause? What course of action should be taken if this is the case?
Hypersensitivity.
Consider withdrawal if rash or signs of hypersensitivity syndrome develop.
More common in patients with history of allergy or rash from other antiepileptics
106
What is the mechanism of action of phenytoin?
Inhibition of voltage-gated sodium channels, thus preventing repetitive firing of action potentials.
107
What is the therapeutic range of phenytoin?
10-20 mg/L (40-80 micromol/L).
108
Which brand specific category does phenytoin fall into? What does this mean?
One. Patient's must be maintained on the same brand.
(Note also differences in availability between phenytoin base and phenytoin sodium)
109
Describe the kinetics of phenytoin?
Non-linear.
A small dose increase can produce a large increase in plasma conc. (and vice versa for missed doses)
110
Give some of the red flag symptoms associated with phenytoin use.
Toxicity, skin disorders, hepatotoxicity, blood disorders, suicidal thoughts, low levels of vitamin D.
111
Give some of the symptoms of phenytoin toxicity.
Nystagmus, double vision, slurred speach, ataxia (balance and co-ordination issues), confusion, hyperglycaemia.
112
Give some of the symptoms of the skin disorder sometimes seen with phenytoin use.
Rash, toxic epidermal necrolysis.
113
Give some of the symptoms of the hepatotoxicity sometimes seen with phenytoin use.
Jaundice, GI pain, dark urine.
114
Give some of the symptoms of the blood disorders sometimes seen with phenytoin use.
Bleeding, bruising, fever, malaise, mouth ulcers, sore throat.
115
Which ASMs can result in low vitamin D?
What are some of the consequences of low vitamin D levels?
Enzyme-inducing ASMs (e.g. carbamazepine) and valproate
Can cause rickets in children, osteomalacia in adults
Supplementation of 10–20 micrograms (400-800units) recommended
116
Increased plasma concentrations of phenytoin are seen with concomitant use of which drugs?
Amiodarone, chloramphenicol, cimetidine, disulfiram, diltiazem, fluconazole, fluoxetine, miconazole, topiramate, trimethoprim.
117
Reduced plasma concentrations of phenytoin are seen with concomitant use of which drugs?
Rifamicin, St John's Wort, theophylline, itraconazole, ciclosporin.
118
Which ASMs have mood stabilising properties?
**Sodium valproate** and **lamotrigine**
Can be helpful to patients who have comorbid bipolar disorder
However, a reduction in mood on withdrawal of the drug may be noted — patients should be warned about this and counselled to report any sudden depressed mood
119
When does pancreatitis/liver dysfunction associated with sodium valproate usually occur and what is it often associated with?
Usually occurs in the first 6 months of therapy. Often associated with multiple antiepileptic therapy.
120
Raised liver enzymes when using sodium valproate are usually transient. However, how often and for how long should LFTs be checked?
Every 6 months until liver function returns to normal.
121
When should sodium valproate treatment be immediately discontinued?
If abnormally prolonged prothrombin time persists or if signs of liver toxicity present (persistent vomiting and abdominal pain, jaundice, loss of seizure control).
122
Overview of the four main anti-seizure medicines
123
What visual disturbance may patients with secondary angle-closure glaucoma experience when taking topiramate? When does this typically occur?
Acute myopia (short sightedness), typically occurring within one month of starting treatment. Fluid build-up resulting in anterior displacement of the lens and iris have also been reported.
124
If raised intra-ocular pressure occurs when a patient is taking topiramate, what course of action should be taken?
Seek specialist ophthalmological advice, use appropriate measures to reduce intra-ocular pressure, stop topiramate as rapidly as feasible.
125
Visual problems associated with use of vigabatrin usually occur when?
From one month to several years after starting treatment.
126
What may happen to the visual disturbances seen with vigabatrin use when the drug is discontinued?
They usually persist and further deterioration cannot be ruled out.
127
What monitoring is required when a patient is taking vigabatrin?
Visual feild testing before treatment and at 6-monthly intervals.
128
If a patient taking vigabatrin reports new visual symptoms, what course of action should be taken?
Symptoms must be reported and the patient should be reviewed by an ophthalmologist urgently. Gradual withdrawal of vigabatrin should be considered.
129
How should benzodiazepines be administered for anaesthesia?
Only by or under the supervision of experienced personnel with adequate training in anaesthesia and airway management.
130
Most antiepileptics are given twice daily. Which ones are given once daily at bedtime due to their long half-lives?
Lamotrigine, perampanel, phenobarbital, and phenytoin
(LP3)
However large doses can be split to reduces ADRs
131
What should be done if a treatment combination is ineffective?
Revert to the regimen that had the best efficacy and tolerance balance (try and have the patient only on one drug if possible)
132
Which antiepileptic drugs have the highest risk of rebound seizures when withdrawing?
Barbiturates and benzodiazepines
133
When is risk of teratogenicity with antiepileptics highest?
First tremester and if the patient is taking two or more antiepileptics
134
What are the conditions for Pregnancy Prevention Programme?
Must have an annual review and have signed annual risk acknowledgement form
- Check if has updated ARAF at each dispensing
- If they have not signed the form, still dispense and refer them to GP
Must always dispense:
- PIL
- Alert card
Ensure on effective contraception (IUD, coil, progesterone implant)
* Contraceptive pill and barrier methods only considered effective if pill and barrier methods are combined, in which case regular pregnancy testing is recommended
* Note that enzyme-inducing drugs all have the potential to interact with hormonal contraceptives reducing contraceptive efficacy, including the implant and the patch.
* Need non-hormonal contraceptives if taking enzyme inducing ASMs (Depo-provera, copper coil).
* Avoid valproate with progesterone (implant, reduced efficacy of contraceptive)
135
Which antiepileptics are safest in pregnancy?
Lamotrigine and levetiracetam
Lamotrigine and levetiracetam were not associated with an increased risk of fetal loss, intra-uterine growth restriction, or preterm birth
136
How are levetiracetam and lamotrigine affected by physiological changes during pregnancy and post-partum?
**Lamotrigine**
* Increases in oestrogen results in **reduced** lamotrigine levels
* Oestrogen increases throughout pregnancy and drops after giving birth. This results in increased lamotrigine levels which need to be corrected shortly after birth to avoid toxicity
* Levels can also be affected by the combined oral contraceptive pill. Toxicity may occur during pill-free period.
* FSRH has also suggested that desogestrel may **increase** lamotrigine levels
**Levetiracetam**
* **Decreased** plasma concentrations have been shown, dose adjustments may be required
* The precise reason for this effect is not known
137
Which antiepileptic can reduce the effectiveness of oral contraceptives?
Phenytoin
138
What new MHRA alert has been issued about Pregabalin?
Use of Pregabalin in the first trimester is associated with a slightly increased risk of major congenital malformations
Patients should use effective contraception during treatment and avoid use in pregnancy unless necessary
139
All pregnant females with epilepsy, whether taking medication or not, should be encouraged to notify the UK Epilepsy and Pregnancy Register.
True or False?
True
140
Which AEDs are present in breast milk in the highest concentration?
(ZELP)
Zonisamide
Ethosuximide
Lamotrigine
Primidone
(ZELP)
141
Which AEDs are associated with risk of drowsiness in breast-fed babies?
(BPP)
Benzodiazepines, Primidone, Phenobarbital
| BPP
142
Which AEDs can cause withdrawal effects in babies if the mother suddenly stops breast-feeding?
(LPP)
Lamotrigine, Phenobarbital, Primidone
143
Which side effect would require immediate withdrawal of Carbamazepine?
Liver dysfunction/Acute liver disease.
(Leucopenia that is severe, progressive, or associated with symptoms also requires withdrawal - if necessary, under cover of a suitable alternative).
144
Patients on carbamazepine can be supplementated with vitamin D in what circumstances?
In patients who are immobilised for long periods or who have inadequate sun exposure or dietary intake of calcium
145
Contra-indications for carbamazepine?
- Acute porphyrias
- AV conduction abnormalities (unless have a pacemaker)
- History of bone-marrow depression
146
What are the first and second line options for newly diagnosed focal seizures?
**1. Levetiracetam or Lamotrigine**
(You need to focus if your race is with a lambo)
If one is unsuccessful, try the other
**2. Carbamazepine, oxcarbazepine, or zonisamide**
(ZeCOnd Line)
**3. Lacosamide**
If monotherapy is unsuccessful, adjunctive treatment should be considered.
147
What are first line options for all generalised seizures except for absence and myoclonic seizures?
**1. Sodium valproate**
In males, and females unable to have children
**2. Levetiracetam (unlicensed) or lamotrigine**
First line in females of childbearing potential
If monotherapy with either lamotrigine or levetiracetam is unsuccessful, the other of these options should be tried.
If monotherapy is unsuccessful, adjunctive treatment should be considered.
148
Which ASM is first-line treatment for newly diagnosed **generalised** seizures in women of child-bearing potential?
Lamotrigine
However, note interaction with oestrogen (reduced levels with increased oestrogen)
149
What is first and second line for myoclonic seizures?
**1. Sodium valproate (in males, and females unable to have children)**
**2. Levetiracetam (if valproate unsuccessful or in females able to have children)**
Avoid Lamotrigine as worsens myoclonic seizures
Myoclonic seizures (myoclonic jerks) occur in a variety of syndromes, and response to treatment varies considerably
150
What is first and second line for absence seizures?
**1. Ethosuximide**
If treatment with ethosuximide is unsuccessful:
**2. Sodium valproate (for males, and females unable to have children)**
As second-line monotherapy or adjunctive treatment
**3. Lamotrigine or levetiracetam [unlicensed use]**
151
What is first and second line for atonic or tonic seizures?
Atonic or tonic seizures are usually seen in childhood, in specific epilepsy syndromes, or associated with cerebral damage or learning disabilities.
**1. Sodium valproate (males, and females unable to have children)**
**2. Lamotrigine (first in females who are able to have children)**
If treatment with lamotrigine is unsuccessful, consider monotherapy or adjunctive treatment (for all patients) with clobazam, rufinamide [unlicensed use], or topiramate [unlicensed use]
152
Patients with absence, myoclonic seizures, dravet syndrome and Lennox-Gastaut syndrome may have their seizures exacerbated if treated with which antiepileptics?
Carbamazepine, gabapentin, oxcarbazepine, phenytoin, pregabalin, tiagabine, or vigabatrin
(Also lamotrigine for myoclonic seizures)
153
Carbamazepine can exacerbate which type of seizures?
Carbamazepine may exacerbate tonic, atonic, myoclonic and absence seizures - avoid
(Same with oxcarbazepine)
154
Atonic and clonic seizures are usually seen in which patient group? What is the drug of choice for this?
Childhood or associated with cerebral damage or mental retardation
First line: Sodium valproate Lamotrigine can be added
155
What is first and second line for dravet syndrome?
**1. Sodium valproate**
Including in females of childbearing potential, because of the severity of the syndrome and the lack of evidence for other effective first-line options
**2. Consider triple therapy with clobazam and stiripentol as first-line adjunctive therapy.**
A tertiary specialist should be involved in decision making
156
What is first and second line for lennox-gastaut syndrome?
**1. Sodium valproate**
Including in females of childbearing potential, because of the severity of the syndrome and the lack of evidence for other effective first-line options
**2. Lamotrigine** (can be used as adjunctive)
A tertiary specialist should be involved in decision making
157
Cannabidiol (CBD) is only licensed and NICE-approved for children and adults with what type of epilepsy?
Treatment-resistant Lennox-Gastaut and Dravet syndromes
Cannabidiol in conjunction with clobazam was shown to improve efficacy in patients with hard-to-treat seizures
158
Lamotrigine can exercaberate which type of seizures?
Myoclonic - avoid
159
Sodium valproate can increase the plasma concentration of lamotrigine.
True or False?
True
Sodium valproate is a CYP450 inhibitor and potentiates the effect of lamotrigine
These drugs are often prescribed together to make use of their synergistic effects whereby valproate increases the half-life of lamotrigine and decreases its clearance
Dose adjustment may be needed if combined
160
Primidone is converted into what drug?
Phenobarbital
A low initial dose of primidone is essential
161
What drugs can be used to treat epilepsy triggered by menstruation?
Clobazam, acetazolamide (carbonic anhydrase inhibitor)
162
Do brief febrile convulsions need any treatment?
No, may give paracetamol to reduce fever but evidence to support this practice is lacking
However, if prolonged (>5 mins) or recurrent, treat as status epilepticus.
Long-term anticonvulsant prophylaxis for febrile convulsions is rarely indicated
163
Which benzodiazepines can be used in epilepsy management?
Clobazam
(athough lack of evidence in its use)
Most often used intermittently as a ‘rescue’ from seizures or to ‘ward off’ seizures
- E.g. if a person is under stress, predicted to be going without sleep or changing between ASMs or if focal seizures are worsening and progression to a tonic-clonic seizure is feared
- Some women will use it around the time of menstruation if they experience catamenial seizures
| Clonazepam (may have prominent sedation)
164
How do you manage status epilepticus?
**If NO resuscitation facilities available:**
- Buccal midazolam (unlicensed) or rectal diazepam
**If resuscitation facilities available:**
- IV lorazepam
Can administer benzo again after 5-10 mins if no response/recurrence
- Monitor hypotension and for respiratory depression
**If 25 minutes after onset and no response/seizures recur after 2 doses of benzos:**
Give levetiracetam (unlicensed)/phenytoin (slow IV)/phenobarbital
- Contact ICU if seizures continue
- Consider phenobarbital if above ineffective/unsuitable
**If second-line treatment options are unsuccessful:**
- Consider general anaesthesia
Secure the patient's airway, give oxygen, and monitor cardiac and respiratory function
If there is concern that convulsive status epilepticus may recur, an emergency management plan should be agreed with the patient if they do not have one already
165
If after initial treatment of IV lorazepam and there is no response after 25 mins, what should be used?
Phenytoin/phenobarbital/levetiracetam
| If this does not work- anaesthesia
166
When is buccal midazolam used?
How should it be prescribed?
Despite not being licensed for use in adults in the UK, buccal midazolam is recommended by NICE for prevention of status epilepticus
Prescribe by brand
* The two different salts (hydrochloride - buccolam - and maleate - epistatus) which are not interchangeable
* Adult patients should be dispensed the highest strength product unless otherwise stated. The dose should not be made up with multiple administrations of lower strengths.
* Should **not** be kept in the fridge
167
Is long term anticonvulsant prophylaxis recommended for febrile convulsions?
No
168
What should be given to patients in status epilepticus which may be caused by alcohol abuse?
Parenteral thiamine
169
What should be given to patients in status epilepticus which may be caused by pyridoxine deficiency?
Pyridoxine (vitamin B6)
170
Dos and Don'ts for first aid for tonic-clonic seizures
**DO**
* Protect the person from injury (remove harmful objects from nearby)
* Cushion their head
* Look for an epilepsy identity card or identity jewellery — it may give information about the person’s seizures and what to do
* Time how long the clonus (jerking) lasts
* Put the person in the recovery position once seizure has terminated
* Stay with the person until they are fully recovered
* Be calmly reassuring
**DO NOT**
* Restrain the person’s movements;
* Put anything in their mouth
* Try to move them unless they are in danger
* Give them anything to eat or drink until they are fully recovered
* Attempt to bring them round
171
999 only needs to be called if someone is having a seizure under what circumstances?
* First seizure
* Seizure lasts for more than five minutes
* Person has a second seizure without recovery from the first
* They are injured during the seizure
* You believe they need urgent medical attention
172
What are immediate measures to manage status epilepticus?
- Position patient to avoid injury
- Support their breathing (may need to provide oxygen)
- Maintain blood pressure
- Correct any hypoglycaemia
173
What is SUDEP?
What is its incidence rate?
Sudden unexpected death in epilepsy (SUDEP)
Sudden, unexpected death in a person with epilepsy, with or without evidence for a seizure preceding the death (and no other cause of death)
Incidence rate of 1.16 cases per 1,000 people with epilepsy
The risk of SUDEP is increased in pregnant women with epilepsy and for 12 months after birth
174
What are the risk factors for SUDEP?
- Non-adherence
- Alcohol misuse
- Depression and other psychiatric disorders
- Frequent generalised tonic-clonic seizures
- Status epilepticus/prolonged seizures
Pharmacists can help identify these risk factors and, in some cases, (e.g. adherence) address them
175
People with epilepsy are almost ten times more likely to drown than the general population.
What advice should be given to patients?
Pharmacists can provide safety information where appropriate, including taking showers rather than baths where possible, sitting in the shower rather than standing and having someone nearby when bathing, with the door unlocked.
176
What is Psychogenic non-epileptic seizures (PNES)?
How is this distinguished from epilepsy?
Seizures in response to thoughts and feelings linked to present and past traumatic experiences
- Not generated by abnormal electrical activity in the brain
- Commonly misdiagnosed as epilepsy however it is possible to have both epilepsy and PNES
Video-EEG telemetry can distinguish between PNES and epileptic seizures if seizures are captured during recording. EEG indicators of PNES include:
- The length of the seizure — PNES tend to be longer than epileptic seizures;
- Unresponsiveness while the EEG shows the person is not asleep;
- Eye closure in a seizure that is not a generalised tonic-clonic seizure
From the patient’s history, PNES should be suspected if a patient does not respond to ASMs or they have a psychiatric comorbidity
Requires specialist input and patients are usually referred to a neuropsychiatrist for psychotherapy and counselling
177
What are some non-pharmacological methods of managing epilepsy?
**Surgery**
*For patients with refractory focal epilepsy
Patient suitability needs to be carefully assessed with appropriate investigations*
**Vagus nerve stimulation**
*A device which stimulates the left vagus nerve is inserted into the chest to reduce abnormal electrical activity leading to seizures*
**Deep brain stimulation**
*The implantation of stimulating electrodes directly into specific areas of the brain and may be considered when there is not a single lesion or seizure focus suitable for resection.*
**Ketogenic diet (in children)**
*Shown to be effective at reducing seizure frequency, although the evidence is not high quality
No evidence in adults*
Above methods may reduce seizure frequency and severity, but rarely bring seizure freedom
Wearable technology, alarms, monitors and other seizure detectors have not been shown in trials to be effective in reducing seizure frequency
