Anticonvulsants Flashcards
Define epilepsy
A neurological condition causing frequent seizures
Seizures are “sudden changes in behaviour caused by electrical hypersynchronization of neuronal networks in the cerebral cortex”
How do you diagnose epilepsy?
Brain activity can be measured using:
- Electroencephalography (EEG)
- Magnetic resonance imaging (MRI)
What are the types of seizure?
JUST BE AWARE THAT THERE ARE DIFFERENT TYPES OF SEIZURES.
General Seizures: Begins simultaneously in both hemispheres of brain
Seizure types and Symptoms
1) Tonic-clonic seizures: loss of consciousness –> muscle stiffening –> jerking/twitching –> deep sleep –> wakes up
2) Absence seizures: brief staring episodes with behavioural arrest (you can fall over as you lose muscle tone)
3) Tonic/atonic seizures: sudden muscle stiffening/sudden loss of muscle control respectively
4) Myoclonic seizures: sudden, brief muscle contractions
5) Status epilepticus: > 5 min of continuous seizure activity
Partial/ focal Seizures: Begins within a particular area of brain and may spread out
Seizure types and Symptoms
6) Simple: retained awareness/consciousness
Complex: impaired awareness/consciousness
Describe the transmission of nerve impulses through the glutamergic synapse?
1) Voltage-gated Na+ channel (VGSC) opens –> membrane depolarisation
2) Voltage-gated K+ channel (VGKC) opens –> membrane repolarisation
3) Ca2+ influx through voltage-gated calcium channels (VGCCs) –> vesicle exocytosis
- Synaptic vesicle associated (SV2A) protein allows vesicle attachment to presynaptic membrane
4) Glutamate activates excitatory post-synaptic receptors (e.g. NMDA, AMPA and kainate receptors)
VGSC antagonist: e.g Carbamazepine
VGCC antagonist: Ethosuximide (T-type antagonist);
SV2A inhibitor: Levetiracetam
Glutamate receptor antagonist: Topiramate
Describe and list some voltage gated Na+ channel blockers
Sodium channels go from a closed state –> open state –> inactive state before going back to a closed state. These drugs target the channel in the inactive state. All the drugs discussed in this lecture have a fast onset of action and long duration of action.
Carbamazepine
Pharmacodynamics:
- Stabilises inactive state of Na+ channel –> reducing neuronal activity
Indications:
- Tonic-clonic seizures; partial seizures
NB: potential severe side-effects (SJS and TEN - skin conditions) in individuals with HLA-B*1502 allele
Lamotrigine
Pharmacodynamics:
- Inactivates Na+ channels –> reducing glutamate neuronal activity
Indications:
- Tonic-clonic seizures, absence seizures, partial seizures
Describe and list a voltage-gated Ca2+ channel
Ethosuximide
Pharmacodynamics
- T-type Ca2+ channel (typically found in neuronal cells) antagonist –> reduces activity in relay thalamic neurones
Indications:
- Absence seizures
Describe two drugs that affect glutamate exocytosis and receptors
Levetiracetam Pharmacodynamics: - Binds to synaptic vesicle associated protein (SV2A) --> preventing glutamate release Indications: - Myoclonic seizures, partial seizures
Topiramate - used to treat neuropathic pain
Pharmacodynamics
- Inhibits NMDA and kainate receptors (post-synaptic receptors)
- Also affects VGSCs and GABA receptors
Indications:
- Myoclonic seizures
How are GABA neurones activated?
- GABA can be released tonically and also following neuronal stimulation
- GABA activates inhibitory post-synaptic GABAA receptors
- GABA A receptors are chloride (Cl-) channels –> membrane hyperpolarisation
- GABA is taken up by GAT and metabolised by GABA transaminase (GABA-T)
Describe a drug that target GABA A receptors
Diazepam
Pharmacodynamics
- GABA receptor, PAM (positive allosteric modulator) –> increases GABA-mediated inhibition
Pharmacokinetics
- Rectal gel - Fast-onset (within 15 min); half-life (2 hours)
Indications
- Status epilepticus
What drug targets the GABAergic synapse?
Sodium Valproate
Pharmacodynamics:
- Inhibits GABA transaminase –> increases GABA-mediated inhibition
Pharmacokinetics:
- Fast onset (1h); half-life (12h)
Indications:
- Indicated for ALL forms of epilepsy
