L27 - Epilepsy

Question 1

Define a seizure

Answer 1

An electrical event that has a sudden onset and is characterised by hyper-excitability and hyper-synchronised activity of large group of neurons

*It is a defined moment/episode, epilepsy is when there are multiple seizures occurring

Question 2

What are the 4 types of seizures

Answer 2

1) Focal (partial) seizures - abnormal activity in a certain area in the brain
a) Simple (no loss of consciousness)
-Motor, sensory (unusually intense smell), autonomic (sweating, palpations), psychic (hallucinations)
*These seizures also come with auras (déjà vu)
b) Complex (loss of consciousness)
Most arise from the temporal lobe (encompasses limbic system - involved in motion, memory, behaviour)
*Also accompanied by auras (perceptual disturbance) and repetitive behaviours

2) Generalized seizures - involves entire hemisphere
a) Tonic-clonic aka grand mal:
Tonic - Patient loses consciousness without warning, tonic contraction, loud moan from constriction of layrnx

Clonic - superimposed relaxation and constriction of muscles. Next is hyperinhibitory phase where muscles are flaccid and bowel and bladder incontinence

b) Absence aka petit mal
Patient stops abruptly, staring off into space and lasts for 10-45 seconds. Occurs multiple times a day

Question 3

Describe the major drug targets for antiepileptic drugs

Answer 3

Na+ voltage dep channels, T-type Ca2+ channels, GABA receptors, GAT-1, GABA Transaminase

Question 4

Describe what is meant by ‘use-dependent’ in the context of the Na+ channel and why this is important

Answer 4

Carbamazepine, Lamotrigine and Phenytoin block the voltage-dependent channel in the INACTIVE state ONLY during HIGH FREQ FIRING so normal transmission is not affected- channels needs to be activated before it will bind so it can go from active to inactive state

Question 5

What is the absence aka petit mal characterized by on the EEG?

Answer 5

3 Hz spike - similar to a person that is in slow wave sleep

*T-type Ca2+ channels are active during sleep and during these seizures

Question 6

Complex seizures arise from which brain region?

Answer 6

Temporal lobe - is is common to operate and do a resection here

Question 7

T/F - Glu antag approved in AUS

Answer 7

F

Question 8

Characteristics of antiepileptic drugs

Answer 8

• All available orally so can cross BBB
• Most metabolised hepatically by cytochrome p450 family
• Narrow therapeutic index (the drugs can get saturated, so increasing dose will increase the conc A LOT and if dosage is too high, it will be toxic)

Question 9

In what type of epilepsy do you tend to target Ca2+?

Answer 9

Absence seizures as these cahnnels are active during these seizures

Question 10

Besides potentiating GABA A R through benzodiazepines and barbituates - what can enhance GABA action?

Answer 10

Blocking GABA Transporter (GAT-1) using Tigabine

Irreversibly inhibits GABA transaminase using Vigabatrin to prevent breakdown of GABA

Question 11

What drug is used for status epilepticus (i.v.) - repetitive seizures that can be life threatening

Answer 11

Diazepam

Question 12

Why is vigabatrin used with caution?

Answer 12

Causes irreversible visual field constriction in 20 - 40% of patients

Question 13

Why is Valproate used commonly for epilepsy?

Answer 13

Multiple actions - Enhances GABA action, inhibits Na+ and Ca2+ channels

Question 14

Side effects of epilepsy drugs

Answer 14

GENERAL: Sedation -> unsteadiness and nausea, diplopia (double vision) tetratogenicity

IDIOSYNCRATIC: Increased fracture risk (phenytoin, carbamazepine, barbiturates, valproate), enhanced metabolism of oral contraceptive (phenytoin, carbamazepine, phenobarbital)