Anticonvulsants

Question 1

What is an epileptic seizure?

Answer 1

Manifestation of an abnormal or excessive synchronised discharge of a set of cerebral neurones

Question 2

What is epilepsy?

Answer 2

A tendency to recurrent, unprovoked seizures

Question 3

What is the clinical manifestation of epilepsy?

Answer 3

Seizures

Question 4

What is epilepsy classified based on?

Answer 4

Part of the brain that is affected:
Focal epilepsy- Excess discharge being localised to one part of brain
Generalised epilepsy- synchronised discharge affects all areas

Question 5

When does epilepsy develop?

Answer 5

At any stage but there are two distinct peaks:
Early adulthood- where genetic predispositions begin to manifest
Later years- when patients start getting brain injuries e.g. stroke

Question 6

What percentage of epilepsy is caused by genetics?

Answer 6

70%

Question 7

What sort of acquired factors can lead to epilepsy

Answer 7

Tumour
Stroke
Infection
Head injury

Question 8

What can be used to measure brain activity?

Answer 8

Electroencepahlography
Magnetoencephalography
Functional MRI

Question 9

What are the distinctive firing patterns and what are they associated with?

Answer 9

Gamma: awareness - hyperactive 
Beta: awareness - thinking
Alpha: awareness - relaxed
Theta: drowsiness, meditation
Delta: deep-sleep

Question 10

Give a brief summary of glutamergic synapse activity?

Answer 10

Voltage gated NA+ channel opens- membrane depolarisation
Voltage gated K+ channel opens - membrane repolarisation
Ca2+ influx through voltage gated calcium channels - vesicle exocytosis
Glutamate activates excitatory post-synaptic receptors

Question 11

What is carbamazepine?

Answer 11

Voltage gated Na+ channel blocker that is the drug of choice for partial seizures and tonic-clonic seizures. Stabilises inactive state of channel

Question 12

What are the pharmacokinetics of carbamazepine?

Answer 12

Induces the expression of hepatic enzymes
16-30 hour half-life
Dangerous in individuals with HLA-B 1502 allele

Question 13

What is phenytoin?

Answer 13

Voltage gated Na+ channel blocker that is indicated for most forms of epilepsy. It is a class 1b channel blocker.

Question 14

What are the pharmacokinetics of phenytoin?

Answer 14

Fast onset (10 mins) and long half-life (10-20 hours)

Question 15

What is retigabine?

Answer 15

VGKC enhancer- potassium channel opener specific for Kv7 alpha subunit. Only licensed for adjunctive treatment. Fast onset (30 mins) and long (10 hour) half life

Question 16

What is ethosuximide?

Answer 16

T-type Ca channel antagonist

Question 17

When is ethosuximide mainly used?

Answer 17

For absence seizures- long half life (50 hours)

Question 18

What is gabapentin?

Answer 18

Thought to inhibit a2d subunit. Indicated for partial seizures

Question 19

What does levetiracetam do?

Answer 19

It binds to synaptic vesicle associated protein preventing glutamate release. Monotherapy for focal seizures. It has a fast onset (1 hour) and long half life of 10 hours

Question 20

What does topiramate do?

Answer 20

It inhibits GluK5 subunit of kainate receptor. Also affects VGSCs and GABA receptors. It is indicated for most types of epilepsy
Fast-onset (1 hour), long half life (24 hours)

Question 21

What does perampanel do?

Answer 21

It is a selective inhibitor of AMPA receptor. Adjunct for partial seizures. Fast onset (1 hour) long half life (24 hours)

Question 22

List the different types of drugs that affect glutamergic synapses and what they affect?

Answer 22

VGSC antagonist - phenytoin, carbamazepine
VGKC enhancer -retigabine
VGCC antagonist- ethosuximide and gabapentin
SV2a inhibitor- levetiracetam
Glutamate receptor antagonist- perampanel and topiramate

Question 23

Explain how a GABAergic synapse works?

Answer 23

GABA can be released tonically and also following neuronal stimulation
GABA activates inhibitory post-synaptic GABAa receptors
GABAa receptors are chloride channels - membrane hyper polarisation
GABA is taken up by GAT
GABA is metabolised by GABA transaminase (GABA-T)

Question 24

When are benzodiazepines used in epilepsy?

Answer 24

All forms of epilepsy- Fast onset and long half life

Question 25

When are barbiturates (phenobarbital) used?

Answer 25

For most forms of epilepsy except absent seizures

Question 26

What do benzodiazepines and barbiturates target?

Answer 26

GABA receptors

Question 27

What effect do barbiturates have in adults and children?

Answer 27

In adults, they act as a sedative but in children may be the cause of behavioural disturbances.

Question 28

What drugs target the GABAergic synapse?

Answer 28

Tiagabine Sodium valproate Vigabatrin

Question 29

What does tiagabine do?

Answer 29

``` It is a selective inhibitor of GAT-1. It used for adjunctive treatment for partial seizures Fast onset (45 mins) short half life (6h) ```

Question 30

What does sodium valproate do?

Answer 30

It is indicated for all forms of epilepsy and inhibits GABA transaminase. It has fast onset (1h) and has a half life (12 hours)

Question 31

What does vigabatrin do?

Answer 31

It irreversibly inhibits GABA transaminase enzyme. Monotherapy for infantile spasm or an adjunct for partial seizures