CPTP 3.21 Neuropharmacology 6 Antiepileptics Flashcards Preview

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Flashcards in CPTP 3.21 Neuropharmacology 6 Antiepileptics Deck (39)
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1

Define epilepsy

Occasional, sudden, excessive local discharges of grey matter

2

What is a convulsion?

A 'fit': muscular contractions during a seizure

3

What is a seizure?

A period of synchronous discharge of neurones

4

What are anticonvulsants?

Drugs active against seizures

5

What are the potential causes of epilepsy?

• Trauma, tumour or infection of the brain
• Drug withdrawal
• High fever
• Metabolic imbalances
• Heavy metal toxicity

Can also be idiopathic

6

What are the types of epilepsy?

Partial Seizures - where the epileptic focus is localised
• Jacksonian
• Temporal lobe epilepsy
• Psychomotor

Generalised
• Petit mal (absence)
• Grande mal (tonic-clonic)

7

How is brain electrical activity monitored?

What is normal and abnormal when using this?

EEG

Brain activity can be unsynchronised or synchronised when the activity of groups of neurones is summated. Unsynchronised is normal. (IMG 11 shows an example using six neurones). Synchronising suggests it is being caused by some underlying pathology

8

What do the symptoms of epilepsy depend on? Give examples

The location of the epileptic focus

Temporal lobe
• Hallucinations

Motor cortex
• Bizarre movements

9

Define a partial siezure

Synchronous activity with a localised epileptic focus (starting site)

10

Why is temporal lobe epilepsy associated with hallucinations?

It contains auditory and visual processing areas which are overstimulated during synchronous activity

11

Describe petit mal seizures

What causes them?

• Generalised seizures
• Synchronous discharge at all electrode sites at 3Hz
• Short duration and random
• 'Absence' (a brief loss and return of consciousness)
• NO MOTOR SYMPTOMS
• No post ictal coma

Dysfunction in thalamocortical circuits

12

What are grand mal seizures also known as?

Tonic-clonic seizures

13

Describe grand mal seizures, including where they start

Name the type of epilepsy characterised by a similar type of seizure but prolonged and continuous

• No focus at onset
• Involves synchronous discharge at all electrode sites
• Random with a LONG duration
• Post ictal coma occurs
• Two phases:
> 'tonic' (classic arched back away from floor)
> 'clonic' (looks like decerebrate posturing but with bent legs) (IMG 12)

Status epilepticus (prolonged tonic-clonic seizure)

14

What can precipitate and complicate status epilepticus?

Precipitated by:
• Fever and sweating
• Hypertension

Complicated by:
• Hypoxia

15

How are status epilepticus seizures stopped?

Induced coma

16

What are the main excitatory and inhibitory neurotransmitters in the brain?

Excitatory: Glutamate
Inhibitory: GABA

17

which receptors and channels contribute to epileptic activity?

• NMDA
• AMPA
• Subthreshold Na+ channels
• Voltage-gated Ca2+ channels

18

What terminates epileptic activity?

• Glutamate depletion
• Glutamate receptor desensitisation

Hyper-polarisation:
• Na+ channel inactivation
• K+ channel activation

19

How do anticonvulsants work?

They target mediators of neuronal excitability (channels and receptors)
• Increasing GABA transmission
> Positively modulate receptors
> GABA reuptake inhibition
> GABA transaminase inhibition
• Block sodium channels
• Block calcium channels

20

Name the formulary anticonvulsants

• Diazepam (benzodiazepines)
• Sodium Valproate
• Phenytoin
• Carbamazepine
• Barbiturates

21

What can barbiturates and benzodiazepines also be used to treat?

Used as anxiolytics and hypnotics (lowers activity)

22

Describe GABAergic neurotransmission

GABA neurones are found all over the brain, in the form of short interneurones which make up 20% of neurones and are involved in 30% of synapses

23

Describe the GABA receptors receptor types

GABA-A
• Ligand gated ion channel

GABA-B
• G-protein linked receptor

24

Recall how barbiturates and benzodiazepines work

Enhances GABAergic neurotransmission:

Barbiturates
• Inhibits Na+ channels thus preventing action potentials. Also a GABA-A agonist.

Benzodiazepines
• Allosteric modulators of GABA-A receptor
• IMG 12

25

Recall why barbiturates have a small therapeutic window.

They activate GABA-A receptors without the need for endogenous GABA.

Also targets Na+ channels

26

Describe the effect of benzodiazepine agonists on:
• Maximum effect of GABA
• Minimum effect of GABA
• EC50 of GABA

IMG 12
No change in minimum or maximum effect, but lowers EC50 of GABA on receptor

27

Describe GABA synthesis

• Glutamine is taken up
• This is converted into glutamate
• Glutamic acid decarboxylase converts this into GABA

28

How is GABA broken down?

It is broken down by GABA transaminase into succinic semialdehyde

29

What potential do voltage-gated sodium channels open at?

-55mV (threshold)

30

What states do sodium channels exist in?

• Open
• Inactivated
• Resting