M5 L5: anticonvulsant drugs

Question 1

what are seizures

Answer 1

transient neurological dysfunction caused by excessive neuronal of brain, resulting in paroxysmal alteration of behaviour and/or EEG changes

Question 2

whats epilepsy

Answer 2

condition characterized by 2 or more unprovoked seizures

Question 3

causes of seizures

Answer 3

• unknown (50%)
• CNS pathology: trauma, tumor, stroke, meningo/encephalitis
• drug induced: lithium, alc withdrawal

Question 4

look over the classifications of seizures

Answer 4

in slideshow!

Question 5

what are the mechanisms of seizures

Answer 5

1. increase in glutamate pathway
   - excitatory
   - NT: glutamate
   - receptor: NMDA
2. decreased GABA pathway
   - inhibitory
   - NT (neurotransmitter): GABA
   - receptor: GABAa

Question 6

non-pharmacologic treatment of seizures

Answer 6

• avoid precipitating factors
• safety precautions
• diet control - ketogenic diet
• surgery

Question 7

what do antiseizure drugs do

Answer 7

control but do NOT cure seizures

seizures control:
- complete control: ~50% of pts
- partial control: ~25% of pts
- no control: ~25% of pts

Question 8

mech of action for antiseizure drugs

Answer 8

• inhibition of GABA pathways
• GABA increase would inhibit CNS excitation

1. increase GABA activity to inhibit nerve firing -> increase inhibitory input to the neuron, suppress firing:
   - benzodiazepines
   - valproate* (barbiturates)
   - phenobarbital
2. block Na+ channel electrical activity to slow nerve impulses
   - phenytoin
   - valproate*
   - lamotrigine*
   - carbamazepine
3. decrease glutamate release -> decrease excitatory transmission
   - lamotrigine*

Question 9

what anticonvulsant works on all 3 mech of action pathways

Answer 9

topiramate

Question 10

anticonvulsants
GI absorption:
metabolism:
excretion:

Answer 10

GI absorption: 80-100%
metabolism: liver (hydroxylation and conjugation)
excretion: kidney

Question 11

CNS adverse effects for anticonvulsant

Answer 11

• sedation
• tremors and ataxia
• cognitive and visual impairment

Question 12

GI adverse effects for anticonvulsant

Answer 12

nausea, vomiting, diarrhea

Question 13

liver adverse effects for anticonvulsant

Answer 13

elevated liver enzymes

Question 14

immune system adverse effects for anticonvulsant

Answer 14

• benign skin rashes (5-20%)
• severe, potentially fatal skin hypersensitivity reactions (not uncommon)
• weight gain

Question 15

anticonvulsant teratogenic effect

Answer 15

• cause neural tube defect
• ex: valproate
• prevention: avoid during preg, folic acid supplements

Question 16

how to minimize anticonvulsant adverse effects

Answer 16

• monotherapy when possible
• start w a low dose
• slowly increase the dose to reach target “start low, go slow”
• administer w meals
• divide the dose over the day

Question 17

anticonvulsant drug interactions

Answer 17

• most induce hepatic microsomal enzymes
• increase metabolism of concurrently administered drugs
• decrease concurrent drugs therapeutic effect

Question 18

how to minimize anticonvulsant drug interactions

Answer 18

• limit coadministration
• monitor response
• adjust dose

Question 19

anticonvulsant overdose/toxicity

Answer 19

• exaggeration of adverse effects
• most dangerous: respiratory depression
• treatment: supportive measures

Question 20

which antiseizure drugs increase GABA activity to inhibit nerve firing

Answer 20

benzodiazepines, valproate, phenobarbital

Question 21

what antiseizure drugs block Na+ channel electrical activity

Answer 21

phenytoin, valproate, lamotrigine, carbamazepine

Question 22

what antiseizure drugs decrease glutamate release

Answer 22

lamotrigine