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Epilepsy Flashcards

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1
Q

Antiepileptic hypersensitivity syndrome

A

Symptoms: fever, rash, lymphadenopathy
Within 1-8 weeks of exposure
Withdraw if presenting with signs or symptoms

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2
Q

What drugs can cause antiepileptic hypersensitivity syndrome?

A 
Carbamazepine
Lacosamide
Lamotrigine
Oxcarbazapine
Phenobarbital
Phenytoin
Primidone
Rufinamide
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3
Q

Risk of suicidal thoughts and behaviour

A

All antiepileptics carry this risk and may occur one week after starting treatment

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4
Q

Epilepsy and driving

A

Patients who have had a first unprovoked epileptic seizure/ single isolated seizure must not drive for 6 months.
If they have established epilepsy and they are compliant with treatment and follow up, they may drive and must be seizure free for a year and have no history of unprovoked seizures.
Should not drive during medication changes or withdrawal of medication and for 6 months after the last dose.

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5
Q

Epilepsy and pregnancy

A

Valproate- highest risk of serious developmental disorders- must be under the PPP
Increased risk of major congenital malformations- carbamazepine, phenobarbital, phenytoin, and topiramate.
The risk for carbamazepine, phenobarbital, and topiramate was shown to be dose dependent.
There is the possibility of adverse effects on neurodevelopment associated with the use of phenobarbital and phenytoin, and an increased risk of intra-uterine growth restriction with phenobarbital, topiramate, and zonisamide.

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6
Q

Epilepsy and breastfeeding

A

Women taking antiepileptic monotherapy should generally be encouraged to breast-feed, seek advice for combination therapy
All infants should be monitored for sedation, feeding difficulties, adequate weight gain, and developmental milestones.

Primidone, phenobarbital, and the benzodiazepines are associated with an established risk of drowsiness in breast-fed babies and caution is required.

Withdrawal effects may occur in infants if a mother suddenly stops breast-feeding, particularly if she is taking phenobarbital, primidone, or lamotrigine.

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7
Q

Antiepileptics that are readily transferred into breast milk and could cause high serum infant conc.

A

Ethosuximide, lamotrigine, primidone, and zonisamide

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8
Q

Antiepileptics that could cause drug accumulate through breastfeeding due to slower metabolism in infants

A

Phenobarbital and lamotrigine

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9
Q

Treatment of focal seizures

A

First line: carbamazepine and lamotrigine

Alternative: oxcarbazepine, sodium valproate, levetiracetam, pregabalin, gabapentin

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10
Q

What are the different types of generalised seizures?

A

Tonic-clonic seizures
Myoclonic seizures
Absence seizures
Atonic and tonic seizures

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11
Q

Which antiepileptic drugs may require dose changes during pregnancy?

A

Lamotrigine
Carbamazepine
Phenytoin

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12
Q

Treatment of tonic-clonic seizures

A

First line for newly diagnosed: sodium valproate (except in pre-menopausal women)
Alternative: lamotrigine- but may exacerbate myoclonic seizures- but can be given if established epilepsy with generalised tonic-clonic seizures only
Carbamazepine and oxcarbazepine may be considered- may exacerbate myoclonic and absence.

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13
Q

Treatment of absence seizures

A

First line: ethosuximide or sodium valproate (except in pre-menopausal women)
Alternative: lamotrigine

Not recommended: carbamazepine, gabapentin, oxcarbazepine, phenytoin, pregabalin, tiagabine and vigabatrin.

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14
Q

Treatment of myoclonic seizures

A

First line: sodium valproate (except in pre-menopausal women)
Alternative: levetiracetam or topiramate (which has a less-favourable side effect profile)

Sodium valproate+levetiracetam are effective in treating generalised tonic-clonic seizures that coexist with myoclonic in idiopathic generalised epilepsy.

Not recommended: carbamazepine, gabapentin, oxcarbazepine, phenytoin, pregabalin, tiagabine and vigabatrin.

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15
Q

Atonic and tonic seizures

A

Usually seen in childhood
May respond poorly to traditional drugs
First line: sodium valproate (except in pre-menopausal women)
Lamotrigine can be added as adjunct therapy

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16
Q

Epilepsy syndromes

A

Dravet syndrome: sodium valproate or topiramate

Lennox-Gastaut syndrome: sodium valproate or lamotrigine

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17
Q

Carbamazepine

A

Simple and complex focal seizures
Generalised tonic clonic seizures

May exacerbate absence, tonic, atonic and myoconic-avoid

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18
Q

Ethosuximide

A

Absence seizures

also licensed for myoclonic

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19
Q

Pregabalin and gabapentin

A

Focal seizures
Not recommended for absence, tonic, atonic and myoconic
Both also licensed for neuropathic pain and pregabalin is also licensed for generalised anxiety disorder

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20
Q

Lamotrigine

A

Focal seizures
Generalised tonic-clonic seizures
Typical absence seizures in children

Myoclonic seizures may be exacerbated by lamotrigine and it may cause serious rashes, especially in children

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21
Q

Lamotrigine-sodium valproate

A

Sodium valproate increases plasma-lamotrigine concentrations and other enzyme inducing antiepileptics may decrease them.

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22
Q

Levetiracetam

A

Focal seizures

Adjunct for myoclonic seizures in children and tonic-clonic seizures

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23
Q

Phenobarbital

Primidone

A

Tonic-clonic and focal seizures
Can be used in all seizures except absence
May have sedative effects in adults
Rebound seizures may occur on withdrawal

Primidone is mainly converted to phenobarbital

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24
Q

Phenytoin

A

Tonic-clonic and focal seizures
May exacerbate absence or myoclonic
Narrow therapeutic index
Parenteral administration: IV (fosphenytoin which is a pro-drug of phenytoin can be given intramuscularly)

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25
Rufinamide
Adjunctive treatment of seizures in Lennox-Gastaut syndrome
26
Topiramate
Tonic-clonic and focal seizures
27
Sodium valproate
All seizure types Monitor LFTs and FBC Valproic acid- licensed for acute mania associated with bipolar disorder
28
Zonisamide
Focal seizures (for adults and children aged 6 years and above)
29
Clobazam (benzo)
Tonic-clonic and refractory focal seizures | Sedative side effects may be prominent
30
Clonazepam (benzo)
Refractory absence and myoclonic seizures | Sedative side effects may be prominent
31
Initial management of status epilepticus
Position patient to avoid injury Support resp- provision of oxygen Maintain bp Correct hypoglycaemia Parenteral thiamine- if alcohol abuse suspected Pyridoxine hydrochloride- if pyridoxine deficiency suspected (particularly in children and infants)
32
Pharmacological treatment of status epilepticus
Seizures lasting longer than 5 minutes- IV lorazepam (repeat after 10 mins if seizures recur or fail to respond) IV diazepam is effective but carries a high risk of thrombophlebitis (IM diazepam is too slow for status epilepticus) Alternative would be rectal diazepam or buccal midazolam If seizures recur or fail to respond 25 mins after onset, phenytoin (slow IV injection), fosphenytoin or phenobarbital should be used. Fosphenytoin can be given more rapidly and causes fewer injection site reactions than phenytoin. If it's been 45 mins after onset, anaesthesia with thiopental, midazolam or propofol (unlicensed)
33
Treating febrile convulsions
Brief febrile convulsions need no specific treatment; antipyretic medication (e.g. paracetamol), is commonly used to reduce fever and prevent further convulsions. Prolonged febrile convulsions (those lasting 5 minutes or longer), or recurrent febrile convulsions without recovery must be treated actively (as for convulsive status epilepticus). Long-term anticonvulsant prophylaxis for febrile convulsions is rarely indicated.
34
Pre carbamazepine, oxcarbazepine and phenytoin treatment screening
HLA-B*1502 allele in patients of Han Chinese or Thai origin- risk of Steven Johnsons syndrome if this allele present
35
Plasma conc of carbamazepine
4-12mg/litre measured after 1-2 weeks
36
Carbamazepine cessation bipolar disorder
Should be stopped over 4 weeks
37
Signs to be wary of with carbamazepine
Signs of blood, liver or skin disorders- fever, rash, mouth ulcers, bruising or bleeding: seek medical attention Should not be given if liver dysfunction or liver disease: stop treatment
38
Fosphenytoin
Severe cerebrovascular reactions- asystole, ventricular fibrillation, cardiac arrest Hypotension, bradycardia and heart block
39
Monitoring for fosphenytoin
BP Heart rate ECG Respiratory function for the duration of the infusion (observe patient 30 mins after)
40
Fosphenytoin in pregnancy
Changes in plasma-protein binding make monitoring difficult. Monitor unbound fraction.
41
Fosphenytoin in hepatic impairment/hypoalbuminaemia
Reduce dose or infusion rate by 10-25% | Monitor free plasma-phenytoin concentration (instead of total)
42
Fosphenytoin prescription
Must include PE (phenytoin equivalence): | fosphenytoin sodium 1.5mg= phenytoin sodium 1mg
43
Max doses gabapentin
Focal seizures: 1.6g TDS | Peripheral neuropathic pain: 3.6g daily
44
MHRA Gabapentin
1) Respiratory depression, even without concomitant opioid medicines Higher risk: compromised respiratory function, elderly, renal impairment, use of CNS depressants- dose reductions may be required 2) Concerns about abuse with gabapentin and pregabalin- reclassified as Class C controlled substance, Schedule 3, exempt from safe custody req. Fatal risks of gabapentin with alcohol and opioids
45
Lacosamide
``` Focal seizures (over the age of 4) May cause antiepileptic hypersensitivity syndrome ```
46
Lamotrigine
Serious skin reactions incl. Steven-Johnsons syndrome and toxic epidermal necrolysis. Mostly occur in the first 8 weeks of treatment
47
What factors increase the risk of skin reactions with lamotrigine?
Concomitant use of valproate Initial lamotrigine dose higher than normal More rapid dose escalation than recommended
48
Lamotrigine dose reduction in hepatic impairment
Approx 50% in moderate | Approx 75% in severe
49
Tapering of lamotrigine dose
Over 2 weeks, unless serious skin reaction
50
Patient advice lamotrigine
Aplastic anaemia, bone- marrow suppression and pancytopenia associated. Monitor for anaemia, bruising or infection.
51
Oxcarbazepine
Caution in patients who have sensitivity to carbamazepine Antiepileptic hypersensitivity reactions Monitor sodium levels in patients at risk of hyponatraemia
52
Phenytoin cautions
Enteral feeding- interrupt for 2 hours before and after dose | Heart failure, hypotension, respiratory depression
53
Side effects of phenytoin
Pneumonitis Electrolyte imbalance Vitamin D deficiency- consider supplementation Rash- discontinue Bradycardia and hypotension (IV use)- reduce rate of administration
54
Phenytoin toxicity
``` Nystagmus Diplopia Slurred speech Ataxia Confusion Hyperglycaemia ```
55
Total plasma-phenytoin concentration
10-20mg/litre Protein binding may be reduced in the elderly or during pregnancy so may be more appropriate to measure the free plasma phenytoin concentration.
56
Monitoring for phenytoin
ECG | Blood pressure
57
Pregabalin
Taper dose over 1 week when withdrawing | Should be discontinued if sufficient benefit isn't seen within first 8 weeks of reaching maximum tolerated dose
58
Rufinamide
Used in Lennox-Gastaut syndrome
59
Max dose of sodium valproate
2.5g
60
Risk of neurodevelopmental disorders and congenital malformations
Neurodevelopmental disorders: approx. 30-40% risk | Congenital malformations: approx. 10% risk
61
Use of valproate in pregnancy
Contraindicated for migraine prophylaxis (unlicensed use) and bipolar disorder Only considered for epilepsy if there are no other suitable options
62
Side effects of sodium valproate
Dizziness Hepatic dysfunction- STOP if persistent vomiting and abdominal pain, anorexia, jaundice, oedema, malaise, drowsiness or loss of seizure control (this usually occurs in the first 6 months of treatment) Pancreatitis- STOP if abdominal pain, nausea or vomiting develop
63
Valproate dose increased risk of teratogenicity
Greater than 1g daily
64
Monitoring valproate
LFTs before therapy and during first 6 months | FBCs
65
Ketone effect on lab tests
False positive urine tests for ketones
66
Withdrawing valproate
Reduce the dose gradually over 4 weeks
67
Caution with valproate
Systemic lupus erythematosus
68
Topiramate
Associated with acute myopia with secondary angle-closure glaucoma, typically occurring within 1 month of starting treatment. Choroidal effusions resulting in anterior displacement of the lens and iris have also been reported. If raised intra-ocular pressure occurs: seek specialist ophthalmological advice; use appropriate measures to reduce intra-ocular pressure and stop topiramate as rapidly as feasible.
69
Topiramate during pregnancy
Increased risk of congenital malformations during first trimester
70
Dose reduction topiramate
eGFR<70: reduced clearance and longer time to steady state conc. so half usual starting and maintenance dose
71
Vigabatrin
Visual field defects that persist despite discontinuation of the drug Encephalopathic symptoms- marked sedation, stupor, confusion with non-specific slow wave EEG (reduce dose or withdraw)
72
Zonisamide
Avoid overheating and ensure adequate hydration (fatal cases of heat stroke reported in children) Contraindicated in sulphonamide hypersensitivity Avoid breastfeeding for 4 weeks after last dose
73
Phenobarbital
All seizure types except absence
74
Clobazam
Contraindication: respiratory depression Cautions: muscle weakness, organic brain changes
75
Equivalency of benzodiazepines
diazepam 5 mg ≡ alprazolam 250 micrograms ≡ clobazam 10 mg ≡ clonazepam 250 micrograms ≡ flurazepam 7.5–15 mg ≡ chlordiazepoxide 12.5 mg ≡ loprazolam 0.5–1 mg ≡ lorazepam 500 micrograms ≡ lormetazepam 0.5–1 mg ≡ nitrazepam 5 mg ≡ oxazepam 10 mg ≡ temazepam 10 mg
76
Clobzam must be endorsed with
'SLS' as it is not prescribable in NHS primary care except for epilepsy
77
Thiopental (barbiturate)
Used in status epilepticus if all other measures fail and for anaesthesia Should only be administered by, or under the direct supervision of, personnel experienced in its use with adequate training in anaesthesia and airway management, and when resuscitation equipment is available.
78
Risk of driving or skilled tasks after being given sedatives or analgesics for procedures
Short general anaesthetic and intravenous benzos- risk extends to at least 24 hours Dangers of alcohol should also be emphasised
79
Indications of lorazepam
1st line for status epilepticus Short term use in anxiety (and insomnia associated with anxiety) Acute panic attacks Conscious sedation for procedures: Oral- the night before procedure and 1-2hrs before IV- 30-45 mins before procedure IM- 60-90 mins before procedure
80
Contraindication of lorazepam
Lorazepam injections contain benzyl alcohol- avoid in neonates CNS depression Respiratory depression
81
Side effects of lorazepam
Paradoxical increase in hostility and aggression may be due to dose changes Saliva altered Leucopenia
82
Indications of midazolam
Status epilepticus Febrile convulsions Conscious sedation for procedures: 5-10 mins before procedure Convulsions in palliative care
83
Oromucosal midazolam solution
Not licensed for over 18 years old and in children under 3 months
84
Administration of benzos
Should only be administered by, or under the direct supervision of, personnel experienced in its use with adequate training in anaesthesia and airway management, and when resuscitation equipment is available.
85
Reversal agent of benzos
Flumenazil
86
Recovery of benzos for sedation
Midazolam has a fast onset of action and provides a faster recovery than the other benzos such as diazepam. This may be longer in the elderly or with those with a reduced cardiac output.
87
Accumulation of midazolam
Accumulates in adipose tissue- prolongs sedation especially in obesity, hepatic impairment or renal impairment.
88
Strengths of midazolam
High strengths (5mg/ml or 2mg/ml) should be reserved for general anaesthesia, intensive care, palliative care, etc. and not for conscious sedation- use 1mg/ml instead.

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