Wk 32 - Epilepsy 3

Question 1

What are the general principles of the clinical management of epilepsy?

Answer 1

• Aims
• Patient ed
• Pharmacological therapy
• Non-pharmacological therapy

Question 2

Give examples of non-pharmacological therapy

Answer 2

• Lifestyle mod
• Epilepsy surgery - resective + non-resective
• Vagus nerve stimulation + neurostimulation
• Ketogenic diet

Question 3

What should patients be educated on?

Answer 3

• Driving restrictions + employment restrictions
• Avoidance of triggers
• AED therapy: treatment plan, adverse effect + LT therapy

Question 4

What should be included when counselling a patient?

Answer 4

• Nature of epilepsy
• 1st aid
• Avoidance of triggers: sleep deprivation, stress, alcohol
• Risk of seizures
• Legal aspect of driving
• Interactions

Question 5

What are the classes of antiepileptic drugs?

Answer 5

• Establish or 1st gen AEDs

- Modern or second + third AEDs

Question 6

What is the purpose of AEDs?

Answer 6

• Protect against seizures while permitting normal functioning of NS
• MOA: alter balance of neuronal excitation + inhibition

Question 7

What are the different mechanism of actions of AEDs?

Answer 7

• 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

Question 8

Blockade of voltage-gated sodium channel MoA

Answer 8

• Most common MoA
• Drugs bind to inactivated VG Na+ channel -> delay recovery from inactivation -> dec neuronal excitability -> dec repetitive firing + spread of seizures

Question 9

What are the subclasses of blockade of voltage-gated sodium channels?

Answer 9

• Blockers of fast inactivated state: phenytoin, carbamazepine, oxcarbazepine, lamotrigine, rufinamide, eslicarbazepine
• Blockers of slow inactivated state: lacosamide

Question 10

Blockade of voltage-gated calcium channels MoA

Answer 10

Block VG Ca++ channels -> inhibition of pacemaker currents + transmitter release

Question 11

What are the subclasses of blockade of voltage-gated calcium channels?

Answer 11

• 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

Question 12

Give examples of drugs that have positive allosteric modulation at GABAA receptors

Answer 12

• Benzodiazepines
• Barbiturates
• Topiramate

Question 13

Give an example of a drug that inhibit metabolism of GABA via irreversible inhibition of GABA-transaminase

Answer 13

Vigabatrin

Question 14

Give an example of a drug that inhibit synaptic GABA reuptake via competitive inhibitor of GAT-1 transporter

Answer 14

Tiagabine

Question 15

Give an example of a drug that enhances synaptic GABAergic transmission via multiples effects on GABA disposition

Answer 15

Inc synthesis of GABA, inc release of GABA + inhibition of catabolism of GABA: sodium valproate

Question 16

Outline the mechanism of action of inhibition of carbonic anhydrase + give example

Answer 16

• Inhibition of carbonic anhydrase -> localised acidosis -> suppression neuronal excitability
• Acetazolamide, topiramate

Question 17

Outline the mechanism of action of the blockade of AMPA receptors + give examples

Answer 17

• Blockade of AMPA receptors -> dec fast excitatory neurotransmission -> dec seizure generation
• Phenobarbital, topiramate

Question 18

Outline the mechanism of the blockade of NMDA receptors + give examples

Answer 18

• Blockade of NMDA receptors -> dec fast excitatory neurotransmission -> dec seizure generation
• Felbamate

Question 19

Outline the mechanism of action of selective binding to synaptic vesicle protein 2A + give examples

Answer 19

• Selective binding to synaptic vesicle protein 2A (SV2A) -> inhibition of glutamate release -> dec fast excitatory neurotransmission -> dec seizure generation
• Levetiracetam, brivaracetam

Question 20

Give an example of a drug that selectively inhibits presynaptic glutamate release via blockade of presynaptic VG Na+ + Ca ++ channels

Answer 20

Lamotrigine

Question 21

What is the criteria for starting AEDs?

Answer 21

• 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

Question 22

What are the factors influencing choice of AED treatment relating to factors related to the drug?

Answer 22

• MoA
• Strength
• S/e
• Formulation
• Interaction
• Cost