2. Epilepsy

Question 1

What is epilepsy

Answer 1

Seizure caused by hyperexcitable neurons that fire electrical impulses rapidly.

Epilepsy is not the only cause of seizures, e.g hyperglycaemia

Question 2

Epilepsy and driving

Answer 2

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)

Question 3

Epilepsy driving AND exceptions

Answer 3

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

Question 4

When can a patient start driving after 6 months

Answer 4

If its only a single isolated seizure OR first unprovoked seizure

Question 5

Focal Seizures

Answer 5

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

Question 6

Focal seizures treatment

Answer 6

first line: Lamotrigine OR levitiracetam

Question 7

myoclonic seizures treatment

Answer 7

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).

Question 8

Tonic or atonic seizures

Answer 8

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).

Question 9

Generalised seizures

Answer 9

When seizure activity affects both sides of the brain at the same time.
Can cause patients to lose consciousness, EXCEPT in myoclonic seizures

Question 10

Generalised seizures types

Answer 10

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

Question 11

Generalised seizures treatment

Answer 11

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

Question 12

Treatment for men with established tonic-clonic seizures only
(men)

Answer 12

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

Question 13

Treatment for women with established tonic-clonic seizures only
(women)

Answer 13

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

Question 14

Epilepsy treatment regimen

Answer 14

First: monotherapy

Second: If monotherapy does not control seizures, change the AED

Third: Combine at least TWO AED’s for seizure control

Question 15

Importance of staying on the same brand of AED

Answer 15

Switching brands of AED can cause a worsening of side effects

Question 16

AED’s which must be maintained on the same brand:

Answer 16

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

Question 17

AED’s which are up to the clinical judgement of the doctor when/if being prescribed by brand

Answer 17

Valproate, Lamotrigine, Clonezepam, Topiramate

Question 18

AED’s that do not need to be prescribed by brand

Answer 18

Gabapentin, Levitiracetam, Pregablin, Ethosuximide

Question 19

Examples of AED’s

Answer 19

Carbamazepine
Gabapentin, Pregablin
Lamotrigine
Phenytoin
Sodium valproate
Levitiracetam
Phenytoin

Barbiturates: Phenobarbital

Benzodiazepine: Clobazam, Clonazepam, Diazepam, Midazolam

Question 20

AED’s and pregnancy

Answer 20

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

Question 21

AED’s and pregnancy planing

Answer 21

• 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

Question 22

AED’s and breastfeeding

Answer 22

Patients taking a single AED should be encouraged to breastfeed

Monitor infants

Must monitor for drowsiness and withdrawal effects

Question 23

Which AED’s appear in high amounts in breastmilk

Answer 23

zelp:

• Zosinamide
• Ethosuximide
• Lamotrigine
• Primidone

Question 24

AED side effects

Answer 24

• 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

Question 25

Gabapentin can cause severe respiratory depression, high-risk groups at risk of this:

Answer 25

Patients taking CNS depressants (barbiturates, benzodiazepines, Z drugs, opioids, ALOCHOL) Respiratory diseases: Asthna, COPD, impaired respiratory function Neurological disease: renal impairment, elderly

Question 26

Warnings surrounding topiramate

Answer 26

Increased risk of neurodevelopmental disabilities Highly effective contraception should be used

Question 27

AED interactions

Answer 27

**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

Question 28

Phenytoin mechanism of action

Answer 28

Makes neurones in the brain less excitable ## Footnote A Narrow therapeutic index drug

Question 29

Phenytoin therapeutic drug monitoring

Answer 29

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.

Question 30

Phenytoin uses

Answer 30

phenytoin should be avoided in absence and myoclonic seizures -as can worsen them

Question 31

Signs of Phenytoin toxicity

Answer 31

Hands H - hyperglycaemia A - ataxia (affects co-ordination, balance and speech) N - nystagmus (eye rolling) D - dipolopia S - slurred speech and confusion

Question 32

Phenytoin side effects

Answer 32

**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

Question 33

Phenytoin interactions

Answer 33

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

Question 34

Carbamazepine therapeutic range

Answer 34

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

Question 35

Signs of carbamazepine toxicity

Answer 35

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)*

Question 36

Carbamazepine side effects

Answer 36

* **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

Question 37

Carbamazepine interactions

Answer 37

* **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.

Question 38

Carbamazepine interactions (more)

Answer 38

* **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

Question 39

Sodium valproate and pregnancy

Answer 39

* 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.

Question 40

Valproate pregnancy prevention programme

Answer 40

* 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

Question 41

Sodium valproate side effects

Answer 41

* **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

Question 42

Sodium valproate drug interactions

Answer 42

* **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

Question 43

What is status epilepticus

Answer 43

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

Question 44

Status epilepticus treatment

Answer 44

Rectal Diazepam OR Midazolam oromucosal solution Can be repeated once more after 5-10 minutes if necessary