Anticonvulsants for Pharmacology and Therapeutics

Question 1

What is an epileptic seizure?

Answer 1

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

Question 2

What are the main excitatory receptors found on post synaptic glutamateric neurones?

Answer 2

NMDA, Kainate + AMPA

Question 3

What are the 5 types of general seizure?

Answer 3

Tonic-clonic: loss of consciousness, stiffening, jerking, deep sleep, wake
Absence: brief staring episodes with behavioural arrest
Tonic/ atonic: sudden stiffening/ loss of control
Myoclonic: sudden, brief contractions
Status epilepticus: >5 mins continuous seizure

Question 4

What are general and partial seizures?

Answer 4

General: begin simultaneously in both hemispheres
Partial: begin within a particular area of brain + may spread

Question 5

Give the 2 types of partial seizures

Answer 5

Simple: retained consciousness
Complex: impaired consciousness

Question 6

Define epilsepsy

Answer 6

A neurological condition causing frequent seizures

Question 7

How may brain activity be measured to diagnose epilepsy? What may be performed to look for underlying damage?

Answer 7

Electroenecphalography (EEG)

MRI

Question 8

Describe neurotransmission at glutamatergic synapses

Answer 8

VGSC opens causing membrane depolarisation
VGKC opens causing membrane repolarisation
Ca2+ influx through VGCCs causing vesicle exocytosis
(Synaptic vesicle associated protein (SV2A) allows vesicle attachment to presynaptic membrane)
Glutamate activates excitatory post-synaptic receptors

Question 9

Name 2 sodium channel blockers used in epilepsy

Answer 9

Carbamazepine

Lamotrigine

Question 10

Describe the pharmacodynamics, pharmacokinetics and indications for Carbamazepine

Answer 10

Stabilises inactive state of Na+ channel, reducing neuronal activity 
Enzyme inducer (drug-drug interactions)
Fast onset (within 1 hour)
Long half life (16-30 hours) 
Tonic clonic + partital seizures

Question 11

What potential severe side effects may arise in those with HLA-B*1502 allele with Carbamazepine treatment?

Answer 11

SJS + TEN

Severe epidermal hypersensitivity reactions

Question 12

Describe the pharmacodynamics, pharmacokinetics and indications for Lamotrigine

Answer 12

Inactivates Na+ channels, reducing glutamate neuronal activity
Fast onset (within 1 hour)
Long half life (24-34 hours)
Tonic clonic + absence seizures

Question 13

Name a VGCC blocker and describe its pharmacodynamics, pharmacokinetics and indications

Answer 13

Ethosuximide
T-type Ca2+ channel antagonist, reduces activity in relay thalamic neurones
Fast onset
Long half life ~50 hours
Absence seizures

Question 14

Name an SV2A inhibitor and describe its pharmacodynamics, pharmacokinetics and indications

Answer 14

Levetiracetam
Binds SV2A preventing glutamate release
Fast onset (within 1 hour)
Shorter half life (10 hours)
Myoclonic seizures

Question 15

Name a glutamate receptor antagonist and describe its pharmacodynamics, pharmacokinetics and indications

Answer 15

Topiramate 
Inhibits NMDA + Kainate receptors
Also affects VGSCs + GABA receptors
Fast onset (within 1 hour)
Long half life ~20 hours
Myoclonic seizures

Question 16

When can GABA be released?

Answer 16

Tonically

Following neuronal stimulation

Question 17

What is the action of GABA? What type of receptors does it stimulate?

Answer 17

Activates inhibitory post-synaptic GABA A receptors

which are Cl- channels causing membrane hyper polarisation

Question 18

How is GABA removed from the synaptic cleft?

Answer 18

Taken up by GAT + metabolised by GABA transaminase (GABA-T)

Question 19

Describe the pharmacodynamics, pharmacokinetics and indications for Diazepam

Answer 19

GABA receptor, Positive Allosteric Modulator, increases GABA mediated inhibition 
Rectal gel 
Very fast onset (within 15 mins)
Short half life (2 hours)
Status epilepticus

Question 20

Describe the pharmacodynamics, pharmacokinetics and indications for Sodium Valproate

Answer 20

Inhibits GABA-T, thus increases GABA mediated inhibition
Fast onset (within 1 hour)
Fairly long half life (12 hours)
ALL forms of epilepsy