Anticonvulsants for Pharmacology and Therapeutics Flashcards
What is an epileptic seizure?
Sudden changes in behaviour caused by electrical hypersynchronization of neuronal networks in the cerebral cortex
What are the main excitatory receptors found on post synaptic glutamateric neurones?
NMDA, Kainate + AMPA
What are the 5 types of general seizure?
Tonic-clonic: loss of consciousness, stiffening, jerking, deep sleep, wake
Absence: brief staring episodes with behavioural arrest
Tonic/ atonic: sudden stiffening/ loss of control
Myoclonic: sudden, brief contractions
Status epilepticus: >5 mins continuous seizure
What are general and partial seizures?
General: begin simultaneously in both hemispheres
Partial: begin within a particular area of brain + may spread
Give the 2 types of partial seizures
Simple: retained consciousness
Complex: impaired consciousness
Define epilsepsy
A neurological condition causing frequent seizures
How may brain activity be measured to diagnose epilepsy? What may be performed to look for underlying damage?
Electroenecphalography (EEG)
MRI
Describe neurotransmission at glutamatergic synapses
VGSC opens causing membrane depolarisation
VGKC opens causing membrane repolarisation
Ca2+ influx through VGCCs causing vesicle exocytosis
(Synaptic vesicle associated protein (SV2A) allows vesicle attachment to presynaptic membrane)
Glutamate activates excitatory post-synaptic receptors
Name 2 sodium channel blockers used in epilepsy
Carbamazepine
Lamotrigine
Describe the pharmacodynamics, pharmacokinetics and indications for Carbamazepine
Stabilises inactive state of Na+ channel, reducing neuronal activity Enzyme inducer (drug-drug interactions) Fast onset (within 1 hour) Long half life (16-30 hours) Tonic clonic + partital seizures
What potential severe side effects may arise in those with HLA-B*1502 allele with Carbamazepine treatment?
SJS + TEN
Severe epidermal hypersensitivity reactions
Describe the pharmacodynamics, pharmacokinetics and indications for Lamotrigine
Inactivates Na+ channels, reducing glutamate neuronal activity
Fast onset (within 1 hour)
Long half life (24-34 hours)
Tonic clonic + absence seizures
Name a VGCC blocker and describe its pharmacodynamics, pharmacokinetics and indications
Ethosuximide T-type Ca2+ channel antagonist, reduces activity in relay thalamic neurones Fast onset Long half life ~50 hours Absence seizures
Name an SV2A inhibitor and describe its pharmacodynamics, pharmacokinetics and indications
Levetiracetam Binds SV2A preventing glutamate release Fast onset (within 1 hour) Shorter half life (10 hours) Myoclonic seizures
Name a glutamate receptor antagonist and describe its pharmacodynamics, pharmacokinetics and indications
Topiramate Inhibits NMDA + Kainate receptors Also affects VGSCs + GABA receptors Fast onset (within 1 hour) Long half life ~20 hours Myoclonic seizures
When can GABA be released?
Tonically
Following neuronal stimulation
What is the action of GABA? What type of receptors does it stimulate?
Activates inhibitory post-synaptic GABA A receptors
which are Cl- channels causing membrane hyper polarisation
How is GABA removed from the synaptic cleft?
Taken up by GAT + metabolised by GABA transaminase (GABA-T)
Describe the pharmacodynamics, pharmacokinetics and indications for Diazepam
GABA receptor, Positive Allosteric Modulator, increases GABA mediated inhibition Rectal gel Very fast onset (within 15 mins) Short half life (2 hours) Status epilepticus
Describe the pharmacodynamics, pharmacokinetics and indications for Sodium Valproate
Inhibits GABA-T, thus increases GABA mediated inhibition
Fast onset (within 1 hour)
Fairly long half life (12 hours)
ALL forms of epilepsy
