Anticonvulsants

Question 1

Three mechanisms of AEDs

Answer 1

1. Block v-g sodium channels reducing excitability of cell membrane
2. Enhancing GABA-mediated inhibition by enhancing post-synaptic frequency of GABA, inhibiting GABA transaminase, or inhibiting GABA reuptake into neurons and glial cells
3. Inhibiting T-type v-g calcium channels

Question 2

Mechanism of action effective in controlling absence seizures

Answer 2

Inhibiting T-type calcium channels

Question 3

Sodium valporate MoA

Answer 3

blocks v-g sodium channel
inhibits T-type v-g Ca channels
inhibits GABA transaminase

Question 4

AEDs that block v-g sodium channels

Answer 4

Phenytoin
Lamotrigine
Carbamezapine
Sodium valporate

Question 5

AEDs that block T-type v-g Ca channels

Answer 5

Ethosuximide
Gabapentin and Pregabalin
Sodium valporate

Question 6

AEDs that enhance the action of GABA

Answer 6

Benzodiazepines - lorazepam, diazepam, midazolam
Phenobarbital (barbituate)
Tiagabine
Sodium valporate

Question 7

AEDs used for status epilepticus

Answer 7

Benzodiazapines
IV Lorazepam or diazepam in hospital
Rectal/buccal midazolam in the community

Question 8

Tiagabine MoA

Answer 8

Inhibits GAT-1 GABA transporter so inhibits GABA (re-)upake by neurones and glia

Question 9

Describe the MoA of blocking Ca channels

Answer 9

Low voltage (transient) T-type Ca2+ channels are important in determining the rhythmic discharge of thalamic neurones associated with absence seizures.

Reduces Ca2+ entry into cell so reduces neurotransmitter release.

Question 10

Describe the MoA of blocking Na channels

Answer 10

Use-dependent - higher the frequency of firing the greater the block produced.
Depolarisation of a neuron increases the amount of sodium channels in inactivated state – which the drug preferentially binds, preventing channel from returning to resting state and thus reducing the number of functional channels able to generate subsequent APs.

Question 11

Phenobarbital MoA; benzodiazepines MoA

Answer 11

Bind GABAA receptor and increase the frequency of channel openings when GABA is also bound > more inhibitory Cl- into cell, stronger IPSP.

Question 12

Which drugs can be used in absence seizures

Answer 12

Sodium valporate
Ethosuximide
Lamotrigine

Question 13

Sodium valporate side effects

Answer 13

hepatotoxicity 
teratogenic
ataxia & tramour
hair loss 
nausea & diahorrea

Question 14

A common side effect in AEDs (in a fair few)

Answer 14

sedation

Question 15

Which seizures should Carbamezapine not be used for?

Answer 15

absence and myoclonic

Question 16

First line for all seizure types except focal seizures

Answer 16

sodium valporate (then lamotrigene)

Question 17

Lamotrigene side effects

Answer 17

Steven Johnson syndrome and toxic epidermal necrolysis (TEN) -life-threatening skin conditions (hypersensitivity)

Question 18

Carbomezapine side effects

Answer 18

leucopenia (low WBC)
maculopaplar rash (hypersensitivity)
Steven-Johnson syndrome and toxic epidermal necrolysis (life-threatening skin conditions, hypersensitivity reaction) 
nausea & vomiting 
ataxia

Question 19

Ethosixumide side effects

Answer 19

rashes

night terrors

Question 20

Topiramate side effects

Answer 20

weight loss
renal stones
glaucoma

Question 21

First line for focal seizures

Answer 21

Carbamezapine

Question 22

Lamotrigene MoA

Answer 22

Inhibits v-g Na channels on the pre-synaptic membrane stabilizing the RMP
Inhibits glutamate AMPA receptors on the post-synaptic membrane

Question 23

Carbamezapine MoA

Answer 23

Inhibits v-g Na channels on the pre-synaptic membrane stabilizing the RMP

Question 24

Phenytoin MoA

Answer 24

Inhibits v-g Na channels on the pre-synaptic membrane stabilizing the RMP