epilepsy 3

Question 1

what are the general principles of managing epilepsy?

Answer 1

Aims
Patient education
Pharmacological (Drug) therapy
Non-Pharmacological therapy
Lifestyle modification 
Epilepsy surgery –resective & non-resective
Vagus Nerve Stimulation (VNS) & Neurostimulation
Ketogenic diet

Question 2

what are the aims of clinical management of epilepsy?

Answer 2

Control seizures
suppress/prevent epileptic seizures & reduce seizure
severity with minimal adverse events
Return patient to health & reduce seizure-related
mortality & morbidity
Social re-integration
encourage & enable patient to live a normal life with
normal social activities & pursuits
Prevent or reverse associated psychiatric complications

Question 3

what do we educate patients on?

Answer 3

Psychosocial issues
diagnosis-related fear & anxiety
restrictions on driving & driver’s licence
restrictions on seizure-sensitive employment
Life-style changes
avoidance of patient-specific seizure precipitants
AED therapy issues
treatment plan
possible AED adverse effects
implications of long-term therapy & patient compliance

Question 4

what information and counselling do we give to the patient?

Answer 4

Nature of epilepsy
First aid management of seizures
Avoidance of seizure precipitants –sleep deprivation, stress,
exercise, alcohol & caffeine consumption, flashing lights, etc
Risks of seizures (e.g. SUDEP) & advice on common hazards
Legal aspects of driving
Purpose of medication & likely duration
Nature of common adverse effects of medication
Need to take medication regularly
Possible interaction with other drugs

Question 5

what is the mainstay of clinical management of epilepsy?

Answer 5

antiepleptic drugs

Question 6

what are the two broad classes for AEDs?

Answer 6

Established or First Generation AEDs –pre 1990

Modern or Second & Third Generation AEDs –post 1990

Question 7

how do AEDs work?

Answer 7

have remarkable ability to protect against seizures
while permitting normal functioning of nervous system
suppress seizures –but do not influence the underlying
tendency to generate seizures (NOT disease-modifying)
cellular mechanisms of action involve alteration in the
balance between neuronal excitation & inhibition

Question 8

how do they classify the AEDs MOA?

Answer 8

AEDs act via four basic cellular mechanisms
modulation of voltage-dependent ion channels (Na+, Ca++, K+)
enhancement of GABA-mediated inhibitory neurotransmission
attenuation of excitatory (mainly glutamate-mediated)
neurotransmission
modulation of neurotransmitter release via a presynaptic action
most AEDs act via more than one of these
mechanisms
the mechanisms of action of some AEDs remain
unclear

Question 9

what is the main MOA of AEDs?

Answer 9

Blockade of voltage-gated sodium channels
most common mechanism of AED action
drugs bind to inactivated VG Na+ channels delay their
recovery from inactivation neuronal excitability 
repetitive firing & spread of seizures

Question 10

what are the two subclasses of AEDs?

Answer 10

blockers of the fast inactivated state 
Phenytoin, carbamazepine, oxcarbazepine, lamotrigine, 
eslicarbazepine, rufinamide
blockers of the slow inactivated state 
Lacosamide

Question 11

how does AEDs work to block voltage gated calcium channels?

Answer 11

block of VG Ca++ channels inhibition of pacemaker

currents and/or transmitter release

Question 12

what are the two subclasses of AEDs whcih block voltage- gated calcium channels?

Answer 12

blockers of low voltage-activated (T-type) channels
Ethosuximide
Zonisamide, sodium valproate
blockers of high voltage-activated (P/Q & N-type)
channels –via binding to the 2subunit
Gabapentin, pregabalin

Question 13

how do AEDs inhibit GABAergic neurotransmission?

Answer 13

Positive allosteric modulation at GABAA receptors
Benzodiazepines, barbiturates, stiripentol, felbamate,
topiramate, cenobamate
Inhibition of metabolism of GABA –via irreversible
inhibition of GABA-transaminase
Vigabatrin
Inhibition of synaptic GABA reuptake –via competitive
inhibitor of GAT-1 transporter
Tiagabine
Enhancement of synaptic GABAergic transmission
via multiple effects on GABA disposition
Increased synthesis of GABA, increased release of
GABA & inhibition of catabolism of GABA
Sodium valproate

Question 14

how do AEDs inhibit carbonic anhydrase?

Answer 14

Inhibition of carbonic anhydrase localised acidosis
suppression neuronal excitability
Acetazolamide, topiramate, zonisamide

Question 15

how do AEDs block excitatory neurotransmission?

Answer 15

Blockade of AMPA receptors fast excitatory
neurotransmission seizure generation
Perampanel, levetiracetam, phenobarbital, topiramate
Blockade of NMDA receptors fast excitatory
neurotransmission seizure generation
Felbamate

Question 16

how do AEDs modulate neurotransmitter release?

Answer 16

Selective binding to synaptic vesicle protein 2A (SV2A)
inhibition of glutamate release fast excitatory
neurotransmission seizure generation
Levetiracetam, brivaracetam
Selective inhibition of presynaptic glutamate release –
via blockade of presynaptic VG Na+ & Ca++ channels?
Lamotrigine

Question 17

what is the criteria for starting AED?

Answer 17

Diagnosis of epilepsy must be firm
generally after second confirmed epileptic seizure*
Risk of recurrence & nature of seizures must
justify treatment
Good compliance must be likely
Patient should be fully counselled
Patient’s wishes should be taken into account

Question 18

what are the factors giverning the choice of AED?

Answer 18

Seizure type
Epilepsy syndrome
Efficacy
Tolerability & ease of use, adverse effects
Pharmacokinetic profile
Patient’s related medical conditions (co-morbidity &
co-medication)
beneficial or deleterious effects on co-morbid conditions
Cost

Question 19

what are the factors influencing choice of AED treatment?

Answer 19

Factors related to the epilepsy
Personal, patient-related factors
Factors related to the drug

Question 20

what are the factors relating to epilepsy that infleunce the choice of AED treatment?

Answer 20

Syndrome & seizure type
Severity & chronicity (frequency)
Aetiology

Question 21

what are the personal, patient related factors that infleunce the choice of AED treatment?

Answer 21

Age & gender
Co-morbidity (physical & mental)
Social circumstances (employment, education,
domestic, etc)
Emotional circumstances
Attitude to risks of seizures & medication

Question 22

what factros relating to the drug influence the choice of AED treatment?

Answer 22

Mechanism of action
Strength of therapeutic effects
Strength & nature of side-effects
Formulation
Drug interactions & pharmacokinetic properties
Cost