S12.1 Anti-epileptic Drugs Flashcards
Define seizure
Sudden excessive electrical activity in neurones
Define epilepsy
More than one unprovoked seizure episodes
What is the difference between partial and generalised seizures?
Partial seizures – Symptoms reflect area affected.
Generalised seizures – Generated centrally, spread through both hemispheres with loss of consciousness.
What are the primary and secondary causes of seizures?
Primary = idiopathic Secondary = identifiable cause e.g. brain injury, stroke, tumour
What are the two classes of anti-epileptic drugs?
VG Sodium Channel Blockers
Drugs Enhancing GABA Mediated Inhibition
What is the mechanism of VG Sodium Channel Blockers?
Inhibition of VGSC by binding to the internal face. This prolongs their inactivation state, so can’t stimulate another AP. Also reduces probability of high abnormal spiking activity
Describe the uses and pharmacokinetics of carbamazepine
Used to treat generalised tonic-clonic and all partial seizures.
PK: Strong CYP450 enzyme inducer, so initial t1/2 is 30hrs yet with repeated use, the t1/2 becomes 15hrs
Describe the ADRs and DDIs of carbamazepine
ADRs: dizziness, vomiting, variable BP
DDIs: CYP450 inducer so decreases the effect of many drugs e.g warfarin, corticosteroids, oral contraceptives
Describe the uses and pharmacokinetics of phenytoin
Used to treat generalised tonic-clonic and all partial seizures.
PK: CYP450 inducer. Non-linear PK at therapeutic levels so close dose monitoring required.
Describe the ADRs and DDIs of phenytoin
ADRs: gingival hyperplasia, hypersensitivity rashes
DDIs: competitive binding with Valproate to increase levels, reduce oral contraceptive effect
Describe the uses and pharmacokinetics of lamotrigine
Used to treat generalised tonic-clonic, all partial and absence seizures
PK: No CYP450 induction so fewer DDIs
Describe the ADRs and DDIs of lamotrigine
ADRs: some CNS (e.g dizziness), mild rashes
DDIs: adjunct therapy with other AEDs, oral contraceptives reduce its levels, and valproate increases levels
Describe the mechanism of drugs enhancing GABA Mediated Inhibition
GABA is one of main inhibitory receptors in brain. Increased GABA results in increased Cl- current into neurones through Cl channel – this increases threshold for ap generation
Describe the uses and mechanism of sodium valproate
Used to treat primary generalised tonic-clonic seizures.
Increases GABA content of the brain by stimulating GABA synthesising enzymes and inhibiting GABA inactivating enzymes
Describe the ADRs and DDIs of sodium valproate
ADRs: teratogenic, weight gain
DDIs: Antidepressants inhibit action of Valproate,
Antipsychotics antagonise Valproate by lowering convulsive threshold.
Describe the uses and mechanism of benzodiazepines?
Lorazepam and diazepam (for status epilepticus), midazolam (absence seizure).
Act at a distinct receptor site on GABA Chloride channel; this enhances GABA action
Describe the ADRs and DDIs of benzodiazepines
ADRs: sedation, confusion, aggression
DDIs: some adjunctive use
Describe the uses and mechanism of Ethosuximide
Used in absence and general seizures
Mechanism: Prevent depolarisation causing “spike and wave” discharge
What is the mechanism of Levetiracetam?
Binds to synaptic vesicles to inhibit pre-synaptic calcium channel activity, therefore inhibiting neurotransmitter release
Summarise what drug is best to use for each type of seizure
Sodium Valproate for primary generalized seizures.
Carbamazepine as for partial seizures.
Lamotrigine for either, esp for women of childbearing age as least teratogenic.
Benzodiazepines and phenytoin for acute life threatening status epilepticus.
What congenital abnormalities can sodium valproate cause?
Neural tube defects, learning difficulties, facial/digit hypoplasia.
What are the management steps for status epilepticus?
First ABCDE approach, check blood glucose, U+Es.
Give benzodiazepines – IV lorazepam.
If seizure not terminating (5 min) give further dose.
If still not terminating (10 min) give phenytoin and call ITU.
