Anticonvulsants

Question 1

What is epilepsy?

Answer 1

A neurological condition causing frequent seizures.

Question 2

What are seizures?

Answer 2

Seizures are ‘sudden changes in behaviour caused by electrical hypersynchronisation of neuronal networks in the cerebral cortex’.

Question 3

What is the prevalence and incidence of epilepsy?

Answer 3

Between 2-7% of the population.

Incidence increased over the last 30-40 years.

Question 4

How is epilepsy diagnosed?

Answer 4

Brain activity can be measured using electroencephalography (EEG) or MRI.

Question 5

What are the different types of epileptic seizures?

Answer 5

General seizures: tonic-clonic, absence, tonic/atonic, myoclonic, status epilepticus.
Partial focal seizures: simple, complex.

Question 6

What feature is common to all general seizures?

Answer 6

Begin simultaneously in both hemispheres of the brain.

Question 7

What are tonic-clonic seizures?

Answer 7

General seizures.

Loss of consciousness, muscle stiffening, jerking/twitching, deep sleep then wake up.

Question 8

What are absence seizures?

Answer 8

General seizures.

Brief starting episodes with behavioural arrest.

Question 9

What are tonic/atonic seizures?

Answer 9

General seizures.

Sudden muscle stiffening/ sudden loss of muscle control.

Question 10

What are myoclonic seizures?

Answer 10

General seizures.

Sudden, brief muscle contractions.

Question 11

What is status epilepticus?

Answer 11

> 5 minutes of continuous seizure activity.

Question 12

What feature is common to partial focal seizures?

Answer 12

Begin with a particular area of brain and may spread out.

Question 13

What is the difference between simple and complex partial focal seizures?

Answer 13

Simple: retained awareness/consciousness.
Complex: impaired awareness/consciousness.

Question 14

Explain the process of neurotransmission at a glutamatergic synapse.

Answer 14

Voltage gated Na+ channel (VGSC) opens leading to membrane depolarisation.
Voltage gated K+ channel (VGKC) opens leading to membrane repolarisation.
Ca2+ influx through voltage gated calcium channels (VGCCs) leading to vesicle exocytosis- synaptic vesicle associated (SV2A) protein allows vesicle attachment to presynaptic membrane.
Glutamate activates excitatory postsynaptic receptors (e.g. NMDA, AMPA and kainate receptors).

Question 15

Give examples of voltage gated sodium channel blockers.

Answer 15

Carbamazepine.

Lamotrigine.

Question 16

What are the pharmacodynamics of carbamazepine?

Answer 16

Stabilises inactive site of sodium channel, reducing neural activity.

Question 17

Discuss the pharmacokinetics of carbamazepine.

Answer 17

Enzyme inducer.
Onset of activity within 1 hour.
16-30 hour half-life.

Question 18

What are the indications for treatment with carbamazepine?

Answer 18

Tonic-clonic seizures, partial seizures.

Question 19

What is a problem with carbamazepine?

Answer 19

Potential severe side effects (SJS and TEN) in individuals with HLA-B*1502 allele.

Question 20

What are the pharmacodynamics of lamotrigine?

Answer 20

Inactivates sodium channels, reducing glutamate neuronal activity.

Question 21

Discuss the pharmacokinetics of lamotrigine.

Answer 21

Onset of activity within 1 hour.

24-34 hour half-life.

Question 22

What are the indications for treatment with lamotrigine?

Answer 22

Tonic-clonic seizures, absence seizures.

Question 23

Give an example of a voltage gated calcium channel blocker.

Answer 23

Ethosuximide.

Question 24

Discuss the pharmacodynamics of ethosuximide.

Answer 24

T-type calcium channel antagonist, reduces activity in relay thalamic neurons.

Question 25

Discuss the pharmacokinetics of ethosuximide.

Answer 25

Long half-life (50 hours).

Question 26

What are the indications for treatment with ethosuximide?

Answer 26

Absence seizures.

Question 27

Give examples of drugs that interfere with glutamate exocytosis and receptors.

Answer 27

Levetiracetam. | Topiramate.

Question 28

Discuss the pharmacodynamics of levetiracetam.

Answer 28

Binds to synaptic vesicle associated protein (SV2A), preventing glutamate release.

Question 29

Discuss the pharmacokinetics of levetiracetam.

Answer 29

Fast onset (1 hour), half-life of 10 hours.

Question 30

What are the indications for treatment with levetiracetam?

Answer 30

Myoclonic seizures.

Question 31

Discuss the pharmacodynamics of topiramate.

Answer 31

Inhibits NMDA and kainate receptors, also affects voltage gated sodium channels and GABA receptors.

Question 32

Discuss the pharmacokinetics of topiramate.

Answer 32

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

Question 33

What are the indications for treatment with topiramate?

Answer 33

Myoclonic seizures.

Question 34

How does neurotransmission occur at a glutamatergic synapse?

Answer 34

VGSC → depolarisation → VGKC → repolarisation. Ca2+ influx through VGCCs → vesicle exocytosis. SVA2 allows vesicle attachment to membrane. Glutamate activates excitatory postsynaptic receptor.

Question 35

Give examples of pharmacological uses of the glutamatergic synapse.

Answer 35

VGSC antagonist, e.g. carbamazepine. VGCC antagonist, e.g. ethosuximide (T-type antagonist). SV2A inhibitor, e.g. levetiracetam. Glutamate receptor antagonist, e.g. topiramate.

Question 36

How does neurotransmission occur at a GABAergic synapse?

Answer 36

GABA can be released tonically and also following neuronal stimulation. GABA activates inhibitory postsynaptic GABA-A receptors. GABA-A receptors are chloride (Cl-) channels → membrane hyperpolarisation. GABA is taken up by GAT and metabolised by GABA transaminase (GABA-T).

Question 37

Discuss the pharmacodynamics of diazepam.

Answer 37

GABA receptor, PAM - increases GABA-mediated inhibition.

Question 38

Discuss the pharmacokinetics of diazepam.

Answer 38

Rectal gel- fast onset (within 15 minutes), half-life of 2 hours.

Question 39

What are the indications for treatment with diazepam?

Answer 39

Status epilepticus.

Question 40

Discuss the pharmacodynamics of sodium valproate.

Answer 40

Inhibits GABA transaminase, increasing GABA-mediated inhibition.

Question 41

Discuss the pharmacokinetics of sodium valproate.

Answer 41

Fast onset (1 hour), half-life of 12 hours.

Question 42

What are the indications for treatment with sodium valproate?

Answer 42

All forms of epilepsy.