Case 13 SBA Flashcards
First line treatment for focal seizures with or without secondary generalisation
carbamazepine and lamotrigine
second choice treatments for focal seizures with or without secondary generalisation
oxcabazepine, sodium valproate, and levetiracetam
first line treatment for tonic-clonic seizures
sodium valproate
alternative treatment for tonic-clonic seizures and why is it not first line?
lamotrigine may exacerbate myoclonic seizures
treatment for absence seizures
ethosuximide or sodium valproate
treatment for newly diagnosed myoclonic seizures
sodium valproate
alternative treatments for myoclonic seizures
topiramate and levetiracetam
treatment for atonic and tonic seizures
sodium valproate with lamotrigine as adjunct if necessary
Sodium channel modulators that enhance fast activation
Phenytoin, carbamazepine, eslicarbazepine, lamotrigine
Sodium channel modulators that enhance slow inactivation
Lacosamide
Drugs that block t-type calcium channels
Ethosuximide and zonisamide
Calcium channel modulators - alpha-2-delta ligands
Gabapentin, pregabalin
GABA -A receptor allosteric modulators
Clonazepam, diazepam, phenobarbital (benzos ad barbiturates)
GABA uptake/GABA transaminase inhibitors
Tiagabine, vigabatrin
Synaptic vesicle 2A modulators with short-term plasticity
Levetiracetam
Anti-convulsants with mixed mechanisms of action
Topiramate and valproate
Which anti-convulsants can exacerbate absences and myoclonus?
Carbamazepine, oxcarbazepine, phenytoin
Which anti-convulsants are contraindicated in myoclonic epilepsies and can worsen seizures?
Gabapentin, pregabalin, tiagabine, vigabatrin
Which anti-convulsants can induce absence status epilepticus?
Tiagabine and vigabatrin
Which anti-convulsants have the lowest and highest risk of foetal malformations?
Valproate - 9.3%
Lamotrigine - 2.0%
Phenytoin effects on foetus
Craniofacial abnormalities and mild mental retardation
Side effects of phenytoin
Dose-dependent neurological, hirsutism, gingival hyperplasia, impaired insulin secretion, mild neuropathy, rash
Acute intoxication with carbamazepine effects
Stupor, coma, hyperirritability, convulsions, respiratory depression
Long-term side effects of carbamazepine
Drowsiness, vertigo, ataxia, diplopia, blurred vision, increased seizure frequency
Lamotrigine side effects
Rash - Stevens-Johnson syndrome, toxic epidermal necrolysis, rash-related death
Valproate side effects
Depression, ataxia, tremor, GI effects, hepatotoxicity and pancreatitis, prolonged actions of other drugs
Topiramate side effects
Somnolence, weight loss, fatigue, nervousness, may precipitate kidney stones
Tiagabine side effects
Dizziness, tremor, difficulty concentrating, depression, ataxia, somnolence, seizures
Perampanel side effects
Somnolence, anxiety, confusion, imbalance, diplopia, dizziness, GI upset
Rarely: hostility, aggression, suicidal ideation
Felbamate side effects
Both very rare
Aplastic anaemia with 30% fatality
Hepatic failure with 40% fatality
Levetiracetam side effects seen in 13%
Agitation, hostility, apathy, anxiety, emotional liability, depression
Levetiracetam side effects seen in 1%
Serious psychiatric effects: hallucinations, suicidal thoughts, psychosis
Phenytoin mechanism of action
Voltage-dependent blockade of fast sodium current through prolongation of inactivated state which prevents repetitive firing
Phenytoin anti-convulsant use
Licensed in tonic-clonic and focal
May exacerbate absence and myoclonic
Phenytoin pharmacokinetics
Narrow therapeutic window, non-linear, complex drug-drug interactions
Carbamazepine mechanism of action
Limits repetitive firing of action potentials evoked by a sustained depolarisation (sodium channels)
Carbamazepine usage
Primary drug for generalised and focal seizures
Also used for trigeminal neuralgia
Clinical implications of carbamazepine pharmacokinetics
Short half-life so requires dose three times daily
Lacosamide mechanism of action
Selectively enhances sodium channel slow activation resulting in stabilisation of hyperexcitable neuronal membranes, inhibition of neuronal firing, and reduction in long-term channel availability without affecting psychological function
Lamotrigine mechanism of action
Acts on both sodium and calcium channels. Suppresses sustained rapid firing of neurons via inactivated state
Calcium channel effects of lamotrigine
May account for efficacy in childhood seizures and also leads to a decrease in synaptic release of glutamate
Valproate mechanisms of action (5)
Prolongs inactivated state of sodium channels
Inhibits low-threshold t-type calcium channels
Inhibits GABA transaminase
Up-regulates glutamate decarboxylase
Inhibits histone deacetylase
Zonisamide mechanism of action (4)
Slows activation of sodium channels
Blocks t-type calcium channels
Possible AMPA-R effects
Enhances large-conductance calcium-activated potassium candles by decreasing mean closed time
Zonisamide usage
Focal seizures with or without secondary generalisation
Topiramate mechanism of action
Reduces sodium channels by inactivated state
Activates hyperpolarising potassium current
Enhances post-synaptic GABA-A receptor current
Inhibits AMPA-kainate subtypes of glutamate receptors
Barbiturate and benzodiazepine mechanism of action
Positive allosteric modulators of GABA-A receptors
Diazepam use as anti-convulsant
First choice for status epilepticus with phenytoin for longer relief
Gabapentin mechanism of action
Elevates GABA synthesis via glutamate decarboxylase and branched chain aminotransferase
Inhibits release through binding to alpha-2-delta subunit of voltage gated n-type calcium channels
Pregabalin use
Adjunctive for partial seizures with or without secondary generalisation
Neuropathic pain
Tiagabine mechanism of action
Potent inhibitor GABA reuptake - preferentially GAT-1 in forebrain and hippocampus
Lipophilic modification of nipecotic acid
Tiagabine usage
Adjunctive in partial
Dose as often as four times daily
Perampanel mechanism of action
Non-competitive AMPA receptor antagonist
Perampanel usage
Adjunct in focal seizures
Felbamate mechanism of action
Positive allosteric modulator of GABA-A and use-dependent binding to glycine site at NMDA receptor reducing current amplitude
Levetiracetam and brivaracetam mechanism of action
Binds to SV2 and reduces short-term plasticity at glutamatergic synapses
May alter protein-protein interactions at synapse
Ethosuximide usage
Choice for absence seizures
Ethosuximide mechanism of action
Reduces t-type calcium channel current without modifying voltage dependence of steady-state inactivation or time course of recovery from inactivation
Why does ethosuximide work for absence seizures?
The t-type currents it blocks are thought to provide the pacemaker current responsible for generating the rhythmic cortical discharge of an absence attack