2. Epilepsy Flashcards
What is epilepsy
Seizure caused by hyperexcitable neurons that fire electrical impulses rapidly.
Epilepsy is not the only cause of seizures, e.g hyperglycaemia
Epilepsy and driving
Patient has established epilepsy, has had NO unprovoked seizures AND
- Seizure free for 1 year
- Seizure Pattern AND No effect on consciousness
- Seizure due to prescribed change or withdrawal (earlier if treatment was replaced for 6 months and no further seizures)
Epilepsy driving AND exceptions
If a patient has a seizure while asleep, they cannot drive for 1 year
EXCEPT:
they ONLY have sleep seizures and it has been 1 year since their first sleep seizure
OR
if it has been 3 years since their last awake seizure
When can a patient start driving after 6 months
If its only a single isolated seizure OR first unprovoked seizure
Focal Seizures
When a seizure begins in a localised area at one side of the brain
Focal seizures can also develop into a generalised tonic-clonic seizure
Focal seizures treatment
first line: Lamotrigine OR levitiracetam
myoclonic seizures treatment
Offer sodium valproate as first-line treatment for myoclonic seizures in:
- boys and men
- girls aged under 10 years and who are unlikely to need treatment when they are old enough to have children
- women who are unable to have children.
Offer levetiracetam as first-line treatment for myoclonic seizures in women and girls able to have children (including young girls who are likely to need treatment when they are old enough to have children).
Tonic or atonic seizures
Offer sodium valproate as first-line treatment for tonic or atonic seizures in:
- boys and men
- girls aged under 10 years and who are unlikely to need treatment when they are old enough to have children
- women who are unable to have children.
Consider lamotrigine as first-line treatment for tonic or atonic seizures in women and girls able to have children (including young girls who are likely to need treatment when they are old enough to have children).
Generalised seizures
When seizure activity affects both sides of the brain at the same time.
Can cause patients to lose consciousness, EXCEPT in myoclonic seizures
Generalised seizures types
Tonic-clonic: when muscle become tense and jerk violently
Myoclonic: brief muscle twicthes
Atonic: Muscles go weak or limp
Tonic: Muscles tense up
Absence: Staring into space
Generalised seizures treatment
For tonic-clonic, myoclonic, atonic, tonic:
First line: Sodium Valproate
*Second line: *Lamotrigine OR Levitracetam
GO FOR THIS if female is of child bearing age
For absence seizures:
First line: Ethosuximide
Treatment for men with established tonic-clonic seizures only
(men)
1st line: Sodium valproate
For men, women who are unable to have children, girls aged under 10 years and who are unlikely to need treatment when they are old enough to have children
Alternatively: lamotrigine
If first-line add-on treatments tried are unsuccessful in people with generalised tonic-clonic seizures, consider 1 of the following second-line add-on treatment options:
lamotrigine
levetiracetam
perampanel
sodium valproate, except in women and girls able to have children
topiramate
Treatment for women with established tonic-clonic seizures only
(women)
1st line: lamotrigine or leviteracetam
If first-line add-on treatments tried are unsuccessful in people with generalised tonic-clonic seizures, consider 1 of the following second-line add-on treatment options:
clobazam
lamotrigine
levetiracetam
perampanel
sodium valproate, except in women and girls able to have children
topiramate
Epilepsy treatment regimen
First: monotherapy
Second: If monotherapy does not control seizures, change the AED
Third: Combine at least TWO AED’s for seizure control
Importance of staying on the same brand of AED
Switching brands of AED can cause a worsening of side effects
AED’s which must be maintained on the same brand:
C-3P
Carbamazepine
Phenytoin
Phenobarbital
Primodone
With generics, make sure the manufacturer is specified
This does not apply when AED’s are being used in other conditions, e.g antipscyhosis
AED’s which are up to the clinical judgement of the doctor when/if being prescribed by brand
Valproate, Lamotrigine, Clonezepam, Topiramate
AED’s that do not need to be prescribed by brand
Gabapentin, Levitiracetam, Pregablin, Ethosuximide
Examples of AED’s
Carbamazepine
Gabapentin, Pregablin
Lamotrigine
Phenytoin
Sodium valproate
Levitiracetam
Phenytoin
Barbiturates: Phenobarbital
Benzodiazepine: Clobazam, Clonazepam, Diazepam, Midazolam
AED’s and pregnancy
Highly teratogenic: valproate
Carbamazepine, Phenytoin, Phenobarbital, Pregablin, Topiramate also increase teratogenic risk —->
Must use highly effective contraception. *Though some AED’s reduce effectiveness of contraceptives
AED’s and pregnancy planing
- Must not stop taking AED
- Must be referred to a specialist
- Must be offered high dose folic acid
- Join UK epilepsy and pregnancy register
- If unplanned –> seek urgent medical advice
AED’s and breastfeeding
Patients taking a single AED should be encouraged to breastfeed
Monitor infants
Must monitor for drowsiness and withdrawal effects
Which AED’s appear in high amounts in breastmilk
zelp:
- Zosinamide
- Ethosuximide
- Lamotrigine
- Primidone
AED side effects
- Dizziness - resolves overtime
-
Anti-epileptic hypersensitivity syndrome -> patients must report signs of a fever, rash or swollen lymph nodes that appear as painful lumps in neck, armpits or groin
More common with CL-3P (Carbamazepine, Lamotrigine, Phenytoin, Phenobarbital, Primidone). Hypersensitivities may also cross over - Suicidal behaiviour. Patients must changes in mood or suicidal thoughts
-
Blood dyscrasias
More commonly caused by phenytoin, sodium valproate, carbamazepine, lamotrigine
Patients must report signs of fever, sore throat, mouth ulcer, bleeding or bruising
Gabapentin can cause severe respiratory depression, high-risk groups at risk of this:
Patients taking CNS depressants (barbiturates, benzodiazepines, Z drugs, opioids, ALOCHOL)
Respiratory diseases: Asthna, COPD, impaired respiratory function
Neurological disease: renal impairment, elderly
Warnings surrounding topiramate
Increased risk of neurodevelopmental disabilities
Highly effective contraception should be used
AED interactions
Carbamazepine, Phenytoin, Phenobarbital are enzyme inducers
Can reduce the effectiveness of hormonal contraceptives
Can reduce the effectiveness of warfarin
Sodium valporate is an enzyme inhibitor
Phenytoin mechanism of action
Makes neurones in the brain less excitable
A Narrow therapeutic index drug
Phenytoin therapeutic drug monitoring
Therapeutic index: 10-20mg/L
A small increase in dose largely increases blood phenytoin levels
Phenytoin is most protein bround - inactive. When it is free it is active
Free-drug levels are monitored in pregnancy, patients less than 3 months old, elderely, in liver failure as free-drug is higher in these patients = increases likelihood of toxicity.
Even if phenytoin blood levels are within the therapeutic range.
Phenytoin uses
phenytoin should be avoided in absence and myoclonic seizures -as can worsen them
Signs of Phenytoin toxicity
Hands
H - hyperglycaemia
A - ataxia (affects co-ordination, balance and speech)
N - nystagmus (eye rolling)
D - dipolopia
S - slurred speech and confusion
Phenytoin side effects
Appearance
coarse facial features
acne
hirsutism
gingival hyerplasia
AED hypersensitivty syndrome
patients must report signs of fever, rash, lumphadenopathy
Skin reactions, from mild to Stevon Johnson syndrome
Han chinese & thai patients are at an increased risk, must undergo pre-screening HLA-B*1502
Blood dyscrasias e.g agrunolocytosis. Patients must report signs of infection, e.g fever, sore throat, mouth ulcers, and bruising, bleeding
Bone disorders
Phenytoin induces vitamin D metabolism
Patients should be offered vitamin D, if they are immobile, have no sun exposure or have low calcium
Phenytoin interactions
Phenytoin is metabolised by cytochrome P450 enzymes.
- Phenytoin interacts with cytochrome inhibitors to increase its levels: amiodarone, azole antifungals, rate-limiting CCB’s SSRI’s, Valproate, Cimetidine, Erythromycin
-
Phenytoin interacts with cytochroe inducers to reduce its levels:
Carbamazepine, Phenobarbital, Rifampicin, St John’s Wort - NSAIDs and Warfarin can displace protein-bound phenytoin
Phenytoin interacts with oral contraceptives and HRT to reduce efficacy
Phenytoin interacts with drugs that lower seizure threshold: antipsychotic, quinolone, SSRI, TCA, tramadol
Interacts with theophylline and digoxin
Carbamazepine therapeutic range
4-12 mg/L
(Always treat patient and not level, patient not experience toxicity, even above level)
Therapeutic range is measured after 1-2 weeks of starting treatment
Signs of carbamazepine toxicity
Handbag
H - hyPOnatraemia and Hallucinations
A - Ataxia and anuria
N - Nystagmus
D - Drowsy, Dizzy, Slurred speech
B - Blurred or double vision
A - arrhythmias
G - Gastro-intestinal effects (N +V)
Also a risk category 1 medicine (C-3P)*
Carbamazepine side effects
-
AED hypersensitivty syndrome
patients must report signs of fever, rash, lumphadenopathy -
Skin reactions, from mild to Stevon Johnson syndrome
Han chinese & thai patients are at an increased risk, must undergo pre-screening HLA-B*1502 - Blood dyscrasias e.g agrunolocytosis. Patients must report signs of infection, e.g fever, sore throat, mouth ulcers, and bruising, bleeding
-
Bone disorders
Phenytoin induces vitamin D metabolism
Patients should be offered vitamin D, if they are immobile, have no sun exposure or have low calcium -
Hepatotoxicity
Patinets must report signs of abdominal pain, persistent vomiting, dark urine, jaundice - HyPOnatraemia
-
Dose-limiting nausea and vomiting, headache, dizziness
To manage this, start with low dose and increase gradually OR use modified release preparations
Carbamazepine interactions
-
Carbamazepine interacts with enzyme inhibitors to increase carbamazepine metabolism thus lowering its levels :
azole antifungals, cimetidine, ciprofloxacin, clarithromycin, erythromcyin, rate-limiting CCB’sm Fluoxteine, Fluvoxamine, Grapefruit juice, isoniazid - phenobarbital, phenytoin, St John’s wort lower carbamazepine levels in the blood
- Carbamazepine is an an enzyme inducer, classically affecting oestrogen and progestogen (reducing efficacy) and warfarin.
Carbamazepine interactions (more)
-
Interacts with drugs that lower seizure threshold = carbamazepine’s anticonvulsant effect is lowered
Antipsychotics, quinolones, SSRI’s, TCA, tramadol -
Interacts with drugs that are also HypOnatraemic:
SSRI’s, TCA’s, MAOI, desmopressin, diuretics, NSAID -
Interacts with drugs that are also Hepatotoxic:
co-amoxiclav, flucloxacillin, tetracycline, fluconazole, isoniazis, methotrexate, statin, sulfasalazine -
Interacts with drugs that also cause blood dyscrasias:
Clozapine
Sodium valproate and pregnancy
- Sodium valproate has a high risk of birth defects, abnormal limbs, mental disorders = TERATOGENIC
- Should only be offered to women of childbearing potential if there are no other suitable alternatives and they are part of the pregnancy prevention programme
- Should be given at the lowest effective dose, in divided doses, as modified release preparations
- Patients that find out they are pregnant must be reffered to specalist. They must not stop medicine or contraception.
Valproate pregnancy prevention programme
- No other suitable alternative
- Patients must be supervised by specialist
- patient must have a negative pregnancy test before starting treatment
- Patient must be on a highly effective form of contraception
1. IUD or implant
OR
2. Combined oral contraceptive AND barrier method - Patients must be provided with a patient guide, patient card and an annual risk acknowledgment form
Sodium valproate side effects
- Blood dyscrasias e.g agrunolocytosis. Patients must report signs of infection, e.g fever, sore throat, mouth ulcers, and bruising, bleeding
-
Bone disorders
Phenytoin induces vitamin D metabolism
Patients should be offered vitamin D, if they are immobile, have no sun exposure or have low calcium -
Hepatotoxicity
Must monitor LFTS
Prolonged prothrombin time due to insufficient platelat factors
Patients must report signs of dark urine, abdominal pain, jaundice, vomiting persistent -
Pancreatitis
Patients must report abdominal pain, nausea, vomiting
Sodium valproate drug interactions
- Sodium valproate is a cytochrome P450 enzyme inhibitor. Interacts with drugs which are substrates for this enzyme, hence raising their blood levels
-
Interacts with drugs that lower seizure threshold = carbamazepine’s anticonvulsant effect is lowered
Antipsychotics, quinolones, SSRI’s, TCA, tramadol -
Interacts with drugs that are also Hepatotoxic:
co-amoxiclav, flucloxacillin, tetracycline, fluconazole, isoniazis, methotrexate, statin, sulfasalazine
What is status epilepticus
When a single seizure lasts longer than 5 minutes, or when multiple seizures occur within 5 minutes
A MEDICAL EMERGENCY - can lead to brain damage/death
Status epilepticus treatment
Rectal Diazepam
OR
Midazolam oromucosal solution
Can be repeated once more after 5-10 minutes if necessary
