Anti-epileptic Flashcards
Definition of epilepsy
Recurrent seizures unprovoked by any systemic or acute neurologic insults
Diagnosis of epilepsy
- exclude metabolic or toxic cause
- LP
- EEG
- neuroimaging
Pathophysiology of epilepsy
Imbalance between excitatory and inhibitory processes
- decreased GABA
- increased glutamate
What is GABA synthesised from?
Amino acid, L-Glutamic acid
How is GABA synthesised?
Glutamic acid decarboxylase (GAD) is presen in neurons
- causes removal of a-carboxyl group
How does GABA inhibit?
- activated GABA A receptor mediates increase in conductance
- increase influx of Cl- ions causes membrane hyperpolerisation
- increase in threshold for generating action potential
- inhibitory action
Goals of therapy in epilepsy
- control seizures
- restore quality of life
- restore neuronal function
- minimize drug adverse effects
- identify and avoid precipitating factors
Excitation ions and neurotransmitter
- inward Na+, Ca++
- glutamate, aspartate
Inhibition ions and neurotransmitter
- inward Cl-
- outward K+
- GABA
MOA of anti-epileptics
- prolong Na+ channel inactivation
- increase Cl- channel
- glutamate receptor antagonism
- Inhibition of T-type Ca++ current
How to choose an anti-epileptic
- based on seizure classification
- patient-specific variables
- characteristics of drug
Drugs that inhibit axonal transmission
- phenytoin
- carbamazepine
- valproate
- lamotrigine
Drugs that potentiate GABA receptors
- benzos
- phenobarb
Why do therapeutic drug monitoring?
- avoid toxicity
- optimize drug/ therapeutic response
- detect changes in pharmacokinetics
- monitor compliance
Classical AEDs
- phenytoin
- phenobarb
- carbamazepine
- valproate
Newer AEDs
- lamotrigine
- Levetiracetam
Drugs that modulate volatge dependent ion channels
- carbamazepine
- phenytoin
- valproid acid
How do benzos work?
- increase the frequency of GABA-mediated chloride channel openings
How does phenobarb work?
- prolongs GABA-mediated chloride channel openings
- block the voltage-dependent sodium channels
Pleiotropic AEDs
- Lamotrigine
- valproate
How does lamotrigine work?
- blocks sodium channels
- may interfere with glutamate release
- inhibits Ca ++ channels
How does valproate work?
- enhances GABA transmission
- blocks sodium channels
- augment K+ channels
Inducers of Cyt p450
- phenobarb
- phenytoin
- carbamazepine
Inhibitor of Cyt p450
Sodium valproate
How does phenytoin work?
- inhibits Na+ channels to inhibit generation of rapid AP
Adverse effects of phenytoin
- CNS sedation
- gum hyperplasia
- hirsuitism
- skin rash hypersensitivity
Interactions with phenytoin
- valproate displaces phenytoin from plasma proteins
- increase cyt p450
Adverse effects of carbamazapine
- diplopia and ataxia
- idiosyncratic skin reaction
- agranulocytosis and aplastic anaemia
Interactions with carbamazepine
- induces microsomal enzymes
- stimulates its own metabolism
Adverse effects of phenobarb
- CNS sedation
- skin rashes if allergic
- tolerance and physical dependence
Interactions with phenobarb
- stimulates cyt p450
- CNS depression with in combo with benzos
Adverse effects of valproate
- elevation of liver enzymes
- birth defects
Interactions with valproate
- displaces phenytoin from plasma proteins
- p450 inhibitor
Adverse effects of lamotrigine
- less CNS sedative
- potentially life-threatening dermatitis
Why might patient have cross-sensitivity to multiple AEDs?
- carbamazepine
- phenytoin
- phenobarb
Are all aromatic AED - get oxidised to arene oxide (which is toxic)
Adverse effects of benzos
- CNS sedative
- tolerance, dependence
Definition of status epilepticus
5 minutes or more of continuous
- clinical or electrographic seizure activity
- recurrent seizure activity without recovery between
General measure in status epilepticus
- start treatment immediately
- ABCs
- blood glucose
- electrolytes and anticonvulsant levels
Stepwise management of status epilepticus
- benzodiazepine
- phenytoin (20mg/kg)
- phenobarbital (20-39mg/kg)
- RSI (propofol) (2-5mg/kg, then infusion)
Problems with AEDs in pregnancy
- sodium valproate higher teratogenic potential
- folate supplementation before pregnancy considered
- pharmacokinetics change, so adjust dose
Problems with ARVs and epilepsy
- phenytoin and carbamazepine are enzyme inducing
- potential drug interactions
- in HIV-infected women of child bearing age, lamotrigine is preferred to valproate
