Flashcards in CPTP 3.21 Neuropharmacology 6 Antiepileptics Deck (39)
Occasional, sudden, excessive local discharges of grey matter
What is a convulsion?
A 'fit': muscular contractions during a seizure
What is a seizure?
A period of synchronous discharge of neurones
What are anticonvulsants?
Drugs active against seizures
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
What are the types of epilepsy?
Partial Seizures - where the epileptic focus is localised
• Temporal lobe epilepsy
• Petit mal (absence)
• Grande mal (tonic-clonic)
How is brain electrical activity monitored?
What is normal and abnormal when using this?
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
What do the symptoms of epilepsy depend on? Give examples
The location of the epileptic focus
• Bizarre movements
Define a partial siezure
Synchronous activity with a localised epileptic focus (starting site)
Why is temporal lobe epilepsy associated with hallucinations?
It contains auditory and visual processing areas which are overstimulated during synchronous activity
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
What are grand mal seizures also known as?
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)
What can precipitate and complicate status epilepticus?
• Fever and sweating
How are status epilepticus seizures stopped?
What are the main excitatory and inhibitory neurotransmitters in the brain?
which receptors and channels contribute to epileptic activity?
• Subthreshold Na+ channels
• Voltage-gated Ca2+ channels
What terminates epileptic activity?
• Glutamate depletion
• Glutamate receptor desensitisation
• Na+ channel inactivation
• K+ channel activation
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
Name the formulary anticonvulsants
• Diazepam (benzodiazepines)
• Sodium Valproate
What can barbiturates and benzodiazepines also be used to treat?
Used as anxiolytics and hypnotics (lowers activity)
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
Describe the GABA receptors receptor types
• Ligand gated ion channel
• G-protein linked receptor
Recall how barbiturates and benzodiazepines work
Enhances GABAergic neurotransmission:
• Inhibits Na+ channels thus preventing action potentials. Also a GABA-A agonist.
• Allosteric modulators of GABA-A receptor
• IMG 12
Recall why barbiturates have a small therapeutic window.
They activate GABA-A receptors without the need for endogenous GABA.
Also targets Na+ channels
Describe the effect of benzodiazepine agonists on:
• Maximum effect of GABA
• Minimum effect of GABA
• EC50 of GABA
No change in minimum or maximum effect, but lowers EC50 of GABA on receptor
Describe GABA synthesis
• Glutamine is taken up
• This is converted into glutamate
• Glutamic acid decarboxylase converts this into GABA
How is GABA broken down?
It is broken down by GABA transaminase into succinic semialdehyde
What potential do voltage-gated sodium channels open at?