Wk 32 - Epilepsy 3 Flashcards
What are the general principles of the clinical management of epilepsy?
- Aims
- Patient ed
- Pharmacological therapy
- Non-pharmacological therapy
Give examples of non-pharmacological therapy
- Lifestyle mod
- Epilepsy surgery - resective + non-resective
- Vagus nerve stimulation + neurostimulation
- Ketogenic diet
What should patients be educated on?
- Driving restrictions + employment restrictions
- Avoidance of triggers
- AED therapy: treatment plan, adverse effect + LT therapy
What should be included when counselling a patient?
- Nature of epilepsy
- 1st aid
- Avoidance of triggers: sleep deprivation, stress, alcohol
- Risk of seizures
- Legal aspect of driving
- Interactions
What are the classes of antiepileptic drugs?
- Establish or 1st gen AEDs
- Modern or second + third AEDs
What is the purpose of AEDs?
- Protect against seizures while permitting normal functioning of NS
- MOA: alter balance of neuronal excitation + inhibition
What are the different mechanism of actions of AEDs?
- Modulation of voltage-dependent ion channels (Na+, Ca++, K+)
- Enhancement of GABA-mediated inhibitory NT
- Attenuation of excitatory (glutamate-mediated)
NT - Modulation of NT release via presynaptic action
Blockade of voltage-gated sodium channel MoA
- Most common MoA
- Drugs bind to inactivated VG Na+ channel -> delay recovery from inactivation -> dec neuronal excitability -> dec repetitive firing + spread of seizures
What are the subclasses of blockade of voltage-gated sodium channels?
- Blockers of fast inactivated state: phenytoin, carbamazepine, oxcarbazepine, lamotrigine, rufinamide, eslicarbazepine
- Blockers of slow inactivated state: lacosamide
Blockade of voltage-gated calcium channels MoA
Block VG Ca++ channels -> inhibition of pacemaker currents + transmitter release
What are the subclasses of blockade of voltage-gated calcium channels?
- Blockers of low voltage activated (T type) channels: sodium valproate
- Blockers of high voltage-activated (P/Q & N-type) channels – via binding to a2d subunit: Gabapentin, pregabalin
Give examples of drugs that have positive allosteric modulation at GABAA receptors
- Benzodiazepines
- Barbiturates
- Topiramate
Give an example of a drug that inhibit metabolism of GABA via irreversible inhibition of GABA-transaminase
Vigabatrin
Give an example of a drug that inhibit synaptic GABA reuptake via competitive inhibitor of GAT-1 transporter
Tiagabine
Give an example of a drug that enhances synaptic GABAergic transmission via multiples effects on GABA disposition
Inc synthesis of GABA, inc release of GABA + inhibition of catabolism of GABA: sodium valproate
Outline the mechanism of action of inhibition of carbonic anhydrase + give example
- Inhibition of carbonic anhydrase -> localised acidosis -> suppression neuronal excitability
- Acetazolamide, topiramate
Outline the mechanism of action of the blockade of AMPA receptors + give examples
- Blockade of AMPA receptors -> dec fast excitatory neurotransmission -> dec seizure generation
- Phenobarbital, topiramate
Outline the mechanism of the blockade of NMDA receptors + give examples
- Blockade of NMDA receptors -> dec fast excitatory neurotransmission -> dec seizure generation
- Felbamate
Outline the mechanism of action of selective binding to synaptic vesicle protein 2A + give examples
- Selective binding to synaptic vesicle protein 2A (SV2A) -> inhibition of glutamate release -> dec fast excitatory neurotransmission -> dec seizure generation
- Levetiracetam, brivaracetam
Give an example of a drug that selectively inhibits presynaptic glutamate release via blockade of presynaptic VG Na+ + Ca ++ channels
Lamotrigine
What is the criteria for starting AEDs?
- Diagnosis of epilepsy must be firm (after 2nd confirmed epileptic seizure)
- Risk of recurrent + nature of seizure must justify treatment
- Good compliance
- Patient fully counselled
What are the factors influencing choice of AED treatment relating to factors related to the drug?
- MoA
- Strength
- S/e
- Formulation
- Interaction
- Cost
