Anticonvulsants Flashcards
What is an epileptic seizure?
Manifestation of an abnormal or excessive synchronised discharge of a set of cerebral neurones
What is epilepsy?
A tendency to recurrent, unprovoked seizures
What is the clinical manifestation of epilepsy?
Seizures
What is epilepsy classified based on?
Part of the brain that is affected:
Focal epilepsy- Excess discharge being localised to one part of brain
Generalised epilepsy- synchronised discharge affects all areas
When does epilepsy develop?
At any stage but there are two distinct peaks:
Early adulthood- where genetic predispositions begin to manifest
Later years- when patients start getting brain injuries e.g. stroke
What percentage of epilepsy is caused by genetics?
70%
What sort of acquired factors can lead to epilepsy
Tumour
Stroke
Infection
Head injury
What can be used to measure brain activity?
Electroencepahlography
Magnetoencephalography
Functional MRI
What are the distinctive firing patterns and what are they associated with?
Gamma: awareness - hyperactive Beta: awareness - thinking Alpha: awareness - relaxed Theta: drowsiness, meditation Delta: deep-sleep
Give a brief summary of glutamergic synapse activity?
Voltage gated NA+ channel opens- membrane depolarisation
Voltage gated K+ channel opens - membrane repolarisation
Ca2+ influx through voltage gated calcium channels - vesicle exocytosis
Glutamate activates excitatory post-synaptic receptors
What is carbamazepine?
Voltage gated Na+ channel blocker that is the drug of choice for partial seizures and tonic-clonic seizures. Stabilises inactive state of channel
What are the pharmacokinetics of carbamazepine?
Induces the expression of hepatic enzymes
16-30 hour half-life
Dangerous in individuals with HLA-B 1502 allele
What is phenytoin?
Voltage gated Na+ channel blocker that is indicated for most forms of epilepsy. It is a class 1b channel blocker.
What are the pharmacokinetics of phenytoin?
Fast onset (10 mins) and long half-life (10-20 hours)
What is retigabine?
VGKC enhancer- potassium channel opener specific for Kv7 alpha subunit. Only licensed for adjunctive treatment. Fast onset (30 mins) and long (10 hour) half life
What is ethosuximide?
T-type Ca channel antagonist
When is ethosuximide mainly used?
For absence seizures- long half life (50 hours)
What is gabapentin?
Thought to inhibit a2d subunit. Indicated for partial seizures
What does levetiracetam do?
It binds to synaptic vesicle associated protein preventing glutamate release. Monotherapy for focal seizures. It has a fast onset (1 hour) and long half life of 10 hours
What does topiramate do?
It inhibits GluK5 subunit of kainate receptor. Also affects VGSCs and GABA receptors. It is indicated for most types of epilepsy
Fast-onset (1 hour), long half life (24 hours)
What does perampanel do?
It is a selective inhibitor of AMPA receptor. Adjunct for partial seizures. Fast onset (1 hour) long half life (24 hours)
List the different types of drugs that affect glutamergic synapses and what they affect?
VGSC antagonist - phenytoin, carbamazepine
VGKC enhancer -retigabine
VGCC antagonist- ethosuximide and gabapentin
SV2a inhibitor- levetiracetam
Glutamate receptor antagonist- perampanel and topiramate
Explain how a GABAergic synapse works?
GABA can be released tonically and also following neuronal stimulation
GABA activates inhibitory post-synaptic GABAa receptors
GABAa receptors are chloride channels - membrane hyper polarisation
GABA is taken up by GAT
GABA is metabolised by GABA transaminase (GABA-T)
When are benzodiazepines used in epilepsy?
All forms of epilepsy- Fast onset and long half life
When are barbiturates (phenobarbital) used?
For most forms of epilepsy except absent seizures
What do benzodiazepines and barbiturates target?
GABA receptors
What effect do barbiturates have in adults and children?
In adults, they act as a sedative but in children may be the cause of behavioural disturbances.
What drugs target the GABAergic synapse?
Tiagabine
Sodium valproate
Vigabatrin
What does tiagabine do?
It is a selective inhibitor of GAT-1. It used for adjunctive treatment for partial seizures Fast onset (45 mins) short half life (6h)
What does sodium valproate do?
It is indicated for all forms of epilepsy and inhibits GABA transaminase. It has fast onset (1h) and has a half life (12 hours)
What does vigabatrin do?
It irreversibly inhibits GABA transaminase enzyme. Monotherapy for infantile spasm or an adjunct for partial seizures
