Epilepsy

Question 1

What are symptoms for epilepsy?

Answer 1

Several episodes of convulsion
Experiences warning signs
Usually unaware for a few minutes
Smacks her lips, picks at clothing, unable to speak during episodes
After an episode they can feel tired, have a headache, prefers to lie down
Memory decline

Question 2

What is a patient history note which may indicate epilepsy?

Answer 2

Several febrile seizures as a young child (treated with diazepam at the time of the seizure but received no ongoing treatment), and family members that are diagnosed with seizures many years ago.

Question 3

What is a type of seizure?

Answer 3

focal (or partial) seizure

Question 4

What do they believe is the cause of the development of seizures?

Answer 4

The development of seizures is thought to be due to an imbalance between inhibitory and excitatory input within certain brain regions and focal seizures most commonly arise from the temporal lobe

Question 5

Describe the physiology of seizures. (components involved)

Answer 5

Question 6

what are the classical drug sites and give examples?

Answer 6

Receptors
- E.g., GABA receptor, AMPA receptor, NMDA receptor

Enzymes
- E.g., GABA transaminase

Ion channels
- E.g., voltage gated sodium and calcium channel

Transport proteins
E.g., GABA transporter

Question 7

How does diazepam work?

Answer 7

It targets GABAa receptor (alpha subunit)

The drug target is on the post-synaptic neurones in the temporal lobe
- For complex, partial focal seizures

The end result, is that the diazepam binds and increases the effectiveness of GABA activation of this receptor (it doesn’t activate the receptor itself)

• This leads to chloride ion influx (in the presence of GABA)
• Which would hyperpolarize the temporal lobe neurone and decrease the effects observed in the abstract

Question 8

What is lamotrigine and pregabalin?

Answer 8

Lamotrigine targets voltage gated sodium channel
Pregabalin targets voltage gated calcium channel

Their drug target is glutamatergic neurones in the temporal lobe

Question 9

what is the end result of lamotrigine?

Answer 9

Blocking the sodium channels reduces neuronal depolarisation which would eventually lead to neurotransmitter release
In this case, glutamate neurotransmission is decreased and there is less excitatory stimulation of the post-synaptic neurone

Question 10

What is the end result of pregabalin?

Answer 10

Blocking the calcium channels prevents calcium influx into the neurone which is required to promote vesicle exocytosis and neurotransmitter release
In this case, glutamate neurotransmission is decreased and there is less excitatory stimulation of the post-synaptic neurone

Question 11

What is levetiracetam?

Answer 11

• It doesn’t act on one of the classical drug targets
• It’s drug target is synaptic vesicle protein SV2A
• The target is at the glutamatergic neurones in the temporal lobe

The end result is…
- The drug interferes with vesicle fusion and therefore reduces exocytosis of glutamate this decreasing the excitatory activation of the post-synaptic neurone

Question 12

What is Valproate?

Answer 12

non-selective drug (acts on multiple targets)
- voltage gated sodium channels, GABA transaminase, voltage gated calcium channels, NMDA receptor blockade, enhance production of GABA

Question 13

what is the biggest problem with non-selective drugs?

Answer 13

the propensity for a larger number of side effects due to hitting so many targets

Question 14

Overall what the possible drugs for epilepsy? (5)

Answer 14

Diazepam
Lamotrigine
Pregabalin
Levetiracetam
Valproate