Epilepsy

Question 1

Definition of epilepsy

Answer 1

A neurological condition causing frequent seizures

Question 2

Seizures are….

Answer 2

sudden changes in behaviour caused by electrical hypersynchronization of
neuronal networks in the cerebral cortex

Question 3

Prevalence & Incidence of epilepsy

Answer 3

Prevalence between 2-7% of the population. COMMON

Incidence increased over the last 30-40 years

Question 4

Diagnosis of epilepsy is done by

Answer 4

EEG - During the seizure will show increased frequency of waveforms.

MRI - detect underlying structural disease

Question 5

Seizures can be split into

Answer 5

Generalised seizures by definition occur in both brain hemispheres.

Partial seizures happen in one focal brain area

Question 6

define the following terms

tonic
clonic
atonic

Answer 6

tonic - muscle stiffening

clonic - jerking/twitching

atonic - Sudden loss of muscle control

Question 7

what is the most common seizure in epilepsy. Describe it

Answer 7

Tonic clonic

loss of consciousness → muscle
stiffening (tonic) → jerking/twitching (clonic) → deep
sleep → wakes up.

Question 8

define Absence seizures

Answer 8

Brief staring episodes with behavioural arrest

Question 9

define Tonic/atonic seizures

Answer 9

Tonic Seizures: Sudden muscle stiffening (increased muscle tone)

Atonic Seizures: Sudden loss of muscle control. Muscles just
relax suddenly, patients will suddenly fall. (Remember the
helmets).

Question 10

define myoclonic Seizures

Answer 10

sudden, brief muscle contractions

Patient may be eating cereal and suddenly gets an arm jerk

Question 11

define Status epilepticus

Answer 11

> 5 min of continuous seizure activity

Medical emergency!!!

Question 12

list Types of Generalised Seizures

Answer 12

Tonic-Clonic
Absence
Tonic/atonic
Myoclonic
Status epilepticus

Question 13

categorise Partial/ focal Seizures

Answer 13

Simple: retained awareness/consciousness

Complex: impaired awareness/consciousness

Question 14

what generally is anticonvulsant therapy based on

Answer 14

inhibit the glutamatergic system or

potentiate the GABAergic system

Question 15

what allows vesicle attachment to presynaptic membrane

Answer 15

Synaptic vesicle associated (SV2A) protein

Question 16

what receptors does glutamate activate

Answer 16

activates excitatory post-synaptic receptors

e.g. NMDA, AMPA & kainate receptors)

Question 17

categorise how drugs inhibiting glutamatergic act - what do they act on

Answer 17

Voltage Gated Sodium
Channel

Voltage Gated Calcium
Channel

Exocytosis and Receptors

Question 18

what drugs affect VGSCs on glutamatergic neurones and how

Answer 18

Carbamezapine - Stabilises inactive state of Na+ channel

Lamotrigine - Inactivates Na+ channels

Question 19

pharmacokinetics of Carbamezapine

Answer 19

Enzyme inducer (drug-drug interactions)

Onset of activity within 1 hour

16-30 hour half-life

Question 20

what is a potential issue/consideration with Carbamezapine

Answer 20

potential severe side-effects (Steven-Johnsons Syndrome and

Toxic Epidermal Necrolysis) in individuals with HLA-B*1502 allele

Question 21

pharmacodynamics of Lamotrigine

Answer 21

Onset of activity within 1 hour

24-34 hour half-life

Question 22

what drugs affect VGCCS and how

Answer 22

Ethosuximide - T-type (Transient calcium channel found in CNS) Ca2+ channel
antagonist

reduces activity in relay thalamic neurones

Question 23

pharmacokinetics of Ethosuximide (t half)

Answer 23

Long half-life (50 hours)

Question 24

what drugs affect exocytosis and receptors

Answer 24

Levetiracetam - Binds to SVA2
(preventing glutamate release)

Topiramate - Inhibits NMDA & kainate receptors

Question 25

Topiramate pharmacokinetics

Answer 25

Fast-onset (1 hour); long half-life (20 hours)

Question 26

how do you remember the indications for each drug acting on the Glutamatergic neurones

Answer 26

drugs acting on VGSC: Tonic-Clonic Seizures drugs acting on T-type VGCC: only useful in absence seizures drugs on exocytosis and rc myoclonic seizures

Question 27

what 2 ways can GABA be released

Answer 27

tonically and following neuronal stimulation

Question 28

what does GABA activate

Answer 28

inhibitory post-synaptic GABAa rc

Question 29

what are GABArc and what does activation of them cause

Answer 29

CL- channels | membrane hyperpolarisation

Question 30

what is GABA taken up by and metabolised by

Answer 30

taken up: GAT | metabolised by: GABA transaminase (GABA - T)

Question 31

what are the drugs affecting the GABAergic synapses and their mechanisms

Answer 31

Diazepam - Positive Allosteric Modulator (potentiator of GABAa receptor) Sodium Valproate - Inhibits GABA transaminase

Question 32

what are the drugs affecting the GABAergic synapses and their mechanisms

Answer 32

Diazepam - Positive Allosteric Modulator (potentiator of GABAa receptor) Sodium Valproate - Inhibits GABA transaminase BOTH INCREASES GABA MEDIATED INHIBITION

Question 33

pharmacokinetics of diazepam

Answer 33

Rectal gel - Fast-onset (within 15 min); half-life (2 hours)

Question 34

Indications of diazepam

Answer 34

Status epilepticus emergency

Question 35

why don't you want people on diazepam for long time

Answer 35

dependancy, withdrawal symptoms, tolerance

Question 36

pharmacokinetics of sodium valproate

Answer 36

Fast onset (1h); half-life (12h)

Question 37

indications of sodium valproate

Answer 37

ALL forms of epilepsy. V commonly used drug.