Epilepsy and anti-epileptic drugs

Question 1

Define epilepsy:

Answer 1

chronic disorder characterised by recurrent seizures which may vary from a brief lapse of attention or muscle jerks to severe and prolonged convulsions

• usually idiopathic
• some result from brain trauma, stroke, intracranial lesions, drug / alcohol abuse
• majority controlled by meds
• aim prevent seizure occurence and severity

Question 2

How do you choose an anti-epileptic?

Answer 2

type of seizure 
epilepsy sydrome 
pharmacokinetic profile 
interactions/ other meds
efficacy 
expected adverse effects
cost 
patient preference

Question 3

What are the general facts about AEDs?

Answer 3

good oral absorption and bioavailability
most metabolised by liver but some excreted unchanged by kidney
classic AEDs generally have more severe CNS sedation than newer ones
due to overlapping mechanisms of action, best drug can be chosen based on minimizing side effects in additional to efficacy

Question 4

What are examples of classic AEDs?

Answer 4

phenytoin 
phenobarbital 
primidone 
carbamazepine 
ethosuximide 
valporate

Question 5

What are examples of newer AEDs?

Answer 5

lamotrigine 
levetiracetam
topiramate
oxcarbazepine 
vigabatrin 
gabapentin/pregabalin

Question 6

What are the adverse effects of AEDs?

Answer 6

sedation - esp with barbituates
cosmetic - phenytoin (gum hypertrophy, acne, hirsutism)
weight gain - valporate, gabapentin 
weight loss- topiramate
reproductive function - valporate
cognitive - topiramate 
behavioural - levetiracetam 
antiepileptic hypersensitivity syndrome

Question 7

What are the targets for AEDs?

Answer 7

increase inhibitory neurotransmitter system - GABA
decrease excitatory neurotransmitter system - glutamate
block voltage- gated inward positive current - na or ca
increase outward positive current - K
many are pleiotropic - act via multiple mechanisms

Question 8

How do barbituates work and what type of epilepsy are they used for ?

Answer 8

increase GABA - all except absence seizure

Question 9

How do benzodiazepine work and what type of epilepsy are they used for ?

Answer 9

increase GABA - status epilepticus

Question 10

How do carbamazepine work and what type of epilepsy are they used for ?

Answer 10

inhibits Na channels - tonic clonic

Question 11

How do phenytoin work and what type of epilepsy are they used for ?

Answer 11

inhibits Na and Ca channels -status epilepticus

Question 12

How do valporate work and what type of epilepsy are they used for ?

Answer 12

increase GABA and inhibits NA channels - partial, Tonic clonic and absence seizures

Question 13

How do levetiracetam work and what type of epilepsy are they used for ?

Answer 13

inhibits synaptic conduction - all

Question 14

How do lamotrigine work and what type of epilepsy are they used for ?

Answer 14

inhibits NA channels - all

Question 15

How do topiramate work and what type of epilepsy are they used for ?

Answer 15

? decrease glutamate, enhance gaba, inhibits Na channels - all

Question 16

How does the treatment for epilepsy work?

Answer 16

monotherapy preferred - better pt compliance
add on therapy to eliminate breakthrough or refractory seizures
therapeutic drug monitoring available for phenytoin and several others require haematological monitoring

Question 17

Why is it important to consider drug-drug interactions with AEDs?

Answer 17

many are notable inducers of cytochrome p450s and a few are inhibitors
phenytoin, carbamazepine and primidone = strong inducers of cytochrome p450s
autoindcers - increase own metabolism
valporate inhibits cytochrome p450s

Question 18

What is status epilepticus?

Answer 18

prolonged seizure or cluster of seizures without return to baseline lasting more than 30 mins
however any seizure >5mins should be treated urgently - longer it lasts more brain damage
medical emergency - mortality in 7-40%
early and aggressive treatment required

Question 19

How do you manage status epilepticus?

Answer 19

airway breathing circulation and seek help
correct any hypoglycaemia
consider parenteral thiamine if alcohol abuse
benzodiazepines -1 st line = lorazepam IV or rectal diazepam, buccal midazolam
followed by long-acting IV AEDs

Question 20

What are the alternative uses of AEDs?

Answer 20

gabapentin/pregabalin, carbamazepine = neuropathic pain
lamotrigine, carbamazepine = bipolar
valporate = mania
topiramate, gabapentin = migraine