Pharmacology 33 - 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
Describe prevalence and incidence of epilepsy
- Prevalence between 2-7% of the population
- Incidence increased over the last 30-40 years
- More focal seizures than previously
Describe diagnosis of epilepsy
Brain activity can be measured using:
- Electroencephalography (EEG)
- Magnetic resonance imaging (MRI - used to look for brain damage/ underlying cause)
List types of general seizures in epilepsy
Begins simultaneously in both hemispheres of brain
- Tonic-clonic seizures: loss of consciousness -> muscle stiffening -> jerking/twitching -> deep sleep -> wakes up
- Absence seizures: brief staring episodes with behavioural arrest
- Tonic/atonic seizures: sudden muscle stiffening (tonic)/sudden loss of muscle control (atonic)
- Myoclonic seizures: sudden, brief muscle contractions
- Status epilepticus: > 5 min of continuous seizure activity
Describe partial/focal seizures
Begins within a particular area of brain and may spread out (can be caused by trauma). Symptoms vary depending on the location of the damage.
- Simple: retained awareness/ consciousness
- Complex: impaired awareness/consciousness
Describe conduction via the glutamatergic synapse
- Voltage-gated Na+ channel (VGSC) opens
resulting in membrane depolarisation - Voltage-gated K+ channel (VGKC) opens, resulting in membrane repolarisation
- Ca2+ influx through voltage-gated calcium channels (VGCCs) causes vesicle exocytosis
- Synaptic vesicle associated (SV2A) protein allows vesicle attachment to presynaptic membrane
- Glutamate activates excitatory post-synaptic receptors (e.g. NMDA, AMPA and kainate receptors)
Describe pharmacodynamics, pharmacokinetics and indications of carbamazepine
Pharmacodynamics
- VGSC blocker
- Stabilises the inactive state of the sodium channel, reducing neuronal activity
Pharmacokinetics
- Enzyme inducer
- Onset of activity within 1 hour
- 16-30 hour half-life
Indications
- Tonic clonic seizures
- Partial seizures
List potential side effects of carbamazepine
Potential severe side-effects (Stevens–Johnson syndrome and toxic epidermal necrolysis) in individuals with HLA-B*1502 allele
Describe pharmacodynamics, pharamcokinetics and indications of lamotrigine
Pharmacodynamics
- Inactivates voltage gated sodium channels, reducing glutamate neuronal activity
Pharmacokinetics
- Onset of activity within 1 hour
- 24-34 hour half life
Indications
- Tonic-clonic seizures
- Absence seizures
Describe pharmacodynamics, pharmacokinetics and indications of ethozuximide
Pharmacodynamics
- T type calcium channel antagonist, which reduces activity in relay thalamic neurones
Pharmacokinetics
- Long half life (50 hours)
- Relatively fast onset of action
Indications
- Absence seizures
Describe the pharmacodynamics, pharmacokinetics and indications of levetiracetam
Pharmacodynamics
- Binds to synaptic vesicle associated protein (SV2A) to prevent glutamate release
Pharmacokinetics
- Fast onset of 1 hour
- Half life 10 hours
Indications
- Myoclonic seizures
Describe pharmacodynamics, pharmacokinetics and indications of topiramate
Pharmacodynamics
- Inhibits NMDA and kainate receptors
- Also affects VGSCs and GABA receptors
Pharmacokinetics
- Fast onset of 1 hour
- Long half life of 20 hours
Indications
- Myoclonic seizures
List drugs used in epilepsy affecting the glutamatergic synapse
- VGSC antagonist: e.g Carbamazepine
- VGCC antagonist: Ethosuximide (T-type antagonist);
- SV2A inhibitor: Levetiracetam
- Glutamate receptor antagonist: Topiramate
Describe GABA neurotransmission
- GABA can be released tonically (irrespective of neuronal excitation) and also following neuronal stimulation
- GABA activates inhibitory post-synaptic GABAa receptors
- GABAa receptors are chloride (Cl-) channels causing membrane hyperpolarisation (reducing neuronal activity)
- GABA is taken up by GAT and metabolised by GABA transaminase (GABA-T)
Describe pharmacodynamics, pharmacokinetics and indications of diazepam in epilepsy
Pharmacodynamics
- GABA receptor, PAM increases GABA-mediated inhibition
Pharmacokinetics
- Rectal gel - Fast-onset (within 15 min)
- Half-life (2 hours)
Indications
- Status epilepticus
Describe pharmacodynamics, pharmacokinetics and indications of sodium valproate in epilepsy
Pharmacodynamics
- Inhibits GABA transaminase
- Increases GABA-mediated inhibition
Pharmacokinetics
- Fast onset (1h)
- Half-life (12h)
Indications
- Indicated for ALL forms of epilepsy
Which drugs are used in tonic clonic seizures?
- Carbamazepine
- Lamotrigine
- Valproate
Which drugs are used in absence seizures?
- Ethosuximide
- Lamotrigine
- Valproate
Which drugs are used in tonic/atonic seizures?
Valproate
Which drugs are used in myoclonic seizures?
- Levetiracetam
- Topiramate
- Valproate
Which drugs are used in status epileptius?
Diazepam
Which drugs are used in simple partial and complex partial seizures?
- Carbamazepine
- Levetiracetam
- Lamotrigine
- Valproate
List the drugs acting on GABAergic synapse
- Diazepam
- Sodium valproate
