Anti-convulsants

Question 1

What are the different types of seizures

Answer 1

General seizures = Affect the whole cortex; starts in both hemispheres at the same time
- Tonic-clonic seizure
- Absence seizure
- Tonic-atonic seizure
- Myoclonic seizure
- Status epilepticus
Partial seizures = Affect one part or paticular area of the brain and may spread out.

Question 2

Describe the symptoms for tonic-clonic seizure

Answer 2

Loss of consciousness
Muscle stiffness
Jerking/twitching
Deep sleep
Wakes up

Question 3

What are the symptoms of an absence seizure?

Answer 3

Brief staring episodes with behaviour arrest (loss of consciousness as well)
Losing muscle tone and falling over is also possible

Question 4

What are the symptoms of a tonic-atonic seizure?

Answer 4

Sudden muscle stiffening and losing control

There is no muscle spasm/twitching so no clonus

Question 5

What are the symptoms of a myoclonic seizure?

Answer 5

Sudden, brief muscle contractions

Jerking movements which are involuntary but are briefer than tonic/clonic seizures

Question 6

What is status epilepticus?

Answer 6

More than 5 minutes of continuous seizure activity (it is basically multiple seizure after another without recovery in between)
This is the most dangerous type of seizure

Question 7

What is a partial focal seizure what is the difference between a simple and a complex partial seizure

Answer 7

A partial seizure is a seizure which begins in a particular area of the brain and my spread out.
Simple = no impaired awareness and/or consciousness
Complex= impaired awareness and/or consciousness

Question 8

Describe glutamatergic neurotransmission

Answer 8

1. Voltage-gated Na+ channel (VGSC) opens = membrane depolarisation
2. Voltage-gated K+ channel (VGKC) opens = membrane repolarisation
3. Ca2+ influx through voltage-gated calcium channels (VGCCs)
4. Synaptic vesicle associated (SV2A) protein allows vesicle attachment to presynaptic membrane for exocytosis
5. Glutamate activates excitatory post-synaptic receptors
   a. NMDA, AMPA & kainite receptors

Question 9

What are the anti-epileptic drugs affecting glutamatergic neurotransmission?

Answer 9

Carbamazepine
Lamotrigine
Ethosuximide
Levetiracetam
Topiramate

Question 10

What do the AEDs affecting glutamatergic neurotransmission have in common =

Answer 10

Fast onset of activity and long duration of action due to their long half-lives

Question 11

How does carbamazepine work

Answer 11

Stabilises inactive state of Na+ channel
This is good as it causes use-dependency blockade meaning that it only blocks the nerve conduction when the neurones are firing excessively (i.e. during a seizure) and so the drugs inhibit seizures without affecting normal cognitive function

Question 12

What are the indications of carbamazepine?

Answer 12

Tonic-clonic seizures and partial seizures
Note: In patients with the HLA-B+1502 polynorphism carbamazepine is dangerous;
Also carbamazepine is an enzyme inducer so need to be carefully monitored as drug-drug interactions can occur

Question 13

How does lamotrigine work

Answer 13

Inactivity of Na+ channels –> less neuronal glutamate neuronal activity. Again use-dependant so good as it does not affect normal cognitive function as much while greatly inhibiting seizures.

Question 14

What are the indications of lamotrigine

Answer 14

Tonic-clonic seizures and absence seizures

Question 15

How does ethosuximide work?

Answer 15

T-type Ca2+ channels antagonist –> reduces activity in relay thalamic neurons (VGCC antagonist)

Question 16

If ethosuximide affects voltage gated calcium channels how come it does not have as much effects in the vasculature?

Answer 16

Ethosuximide is selective for T-type Ca2+ channels. In the vasculature the voltage gated calcium channels are L-type channels which ethosuximide does not bind to.

Question 17

What are the indications of ethosuximide

Answer 17

Absence seizures

Question 18

How does levetiracetam work

Answer 18

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

Question 19

What are the indications of levetiracetam

Answer 19

Myoclonic seizures

Question 20

How does topiramate work

Answer 20

It inhibits the action of glutamate by inhibiting NMDA and kainate receptors
Also affects VGSCs and GABA receptors
It isn’t really selective

Question 21

What are the indications of topiramate

Answer 21

Myoclonic seizures

Although topiramate is mainly used for neuropathic pain more not epilepsy as much

Question 22

Describe GABAergic neurotansmission

Answer 22

1. GABA can be released tonically & also following neuronal stimulation
2. GABA activates inhibitory post-synaptic GABA-A receptors
3. GABA-A receptors are chloride (Cl-) channels => membrane hyperpolarisation
4. GABA is taken up by GAT & metabolised by GABA transaminase (GABA-T)

Question 23

What drugs affect the GABAergic neurotransmission to treat epilepsy

Answer 23

Diazepam and sodium valproate

Question 24

How does Diazepam work?

Answer 24

Diazepam is an positive allosteric modulator (PAM) = it enhances GABA activity once GABA is bound to the GABA-A receptor

Question 25

What are the pharmacokinetics of Diazepam?

Answer 25

Rectal gel
Fast-onset (within 15 minutes)
Half-life 32 h

Question 26

What are the indications of diazepam?

Answer 26

Used for very serious epilepsy - status epilepticus as it has such a fast onset of 15 mins

Question 27

How does sodium valproate work?

Answer 27

Sodium valproate inhibits GABA-T inhibiting GABA breakdown => increasing GABA mediated inhibition - also GABA-T produces GABA into Glutamate so has valproate has a dual effect by also reducing Glutamate produced => reducing Glutamate mediated excitation
OVERALL => Increased inhibition by inhibiting GABA breakdown and inhibiting Glutamate production from GABA breakdown

Question 28

What are the pharmacokinetics of sodium valproate?

Answer 28

Fast onset

Half life = 12h (reasonably long)

Question 29

What are the indications of sodium valproate

Answer 29

ALL forms of epilepsy

Only drug in this list which is indicated for tonic-atonic seizures.