seizure drugs

Question 1

What types of seizures are narrow spectrum seizure drugs good for? Broad spectrum?

Answer 1

narrow spectrum are effective against partial seizures, including secondarily generalized seizures
broad spectrum are effective against both partial and generalized seizures

Question 2

What are the narrow spectrum seizure drugs? Broad spectrum?

Answer 2

narrow: carbamazepine, phenytoin, phenobarbital, gabapentin, tiagabine
broad: valproate, topiramate, lamotrigine, clonazepam

Question 3

What is the only indication for ethosuximide? What is the only indication for lorazepam?

Answer 3

ethosuximide - absence seizures

lorazepam - status epilepticus

Question 4

What anti-epileptic drugs predominantly act by inhibiting voltage gated Na+ channels by stabilizing the inactivated state of the channel?

Answer 4

phenytoin, carbamazepine, valproate, topiramate, lamotrigine

Question 5

What anti-epileptic drugs predominantly act by enhancing GABA-A receptors activity? By increasing synaptic levels of GABA?

Answer 5

Positive allosteric effect on GABA receptor: the benzodiazepines, phenobarbital, topiramate
Increasing synaptic levels of GABA: tiagabine, gabapentin (maybe)

Question 6

What channels are defective in absence seizures? What are the AEDs used against absence seizures?

Answer 6

T-type Ca2+ channels that allow excessive current through them lead to absence seizures.
Effective drugs against absence seizures are: ethosuximide, valproate, clonazepam

Question 7

What AED’s mechanism of action is to inhibit the N/P type Ca2+ channels that mediate neurotransmitter release?

Answer 7

lamotrigine

Question 8

What AED’s mechanism of action is to modulate AMPA glutamate receptors?

Answer 8

topiramate

Question 9

What AED’s mechanism of action is to inhibit carbonic anhydrase?

Answer 9

topiramate

Question 10

What AED’s mechanism of action is to enhance conductance of K+ channels?

Answer 10

valproate

Question 11

What are the initial treatment options for status epilepticus? What should you give if the patient the seizure is refractory to initial treatments?

Answer 11

Initial: benzodiazapenes (lorazepam and diazepam) and fosphenytoin/phenytoin
If refractory: add phenobarbital or valproate
If seizures not controlled after 1 hour, induce general anesthesia

Question 12

In pharmacokinetic theory, what is induction? What is competition?

Answer 12

induction - when drug A increases the gene expression of an enzyme (usually a P450) that breaks down drug B so that drug B is eliminated faster
competition - when drug A and B are broken down by the same enzyme but drug A has a higher affinity so that the rate of elimination for drug B is slowed

Question 13

What enzyme are almost all AED inducers of? What are the implications of this?

Answer 13

All of the older AEDs, phenytoin, carbamazepine, phenobarbital, (and the newer AEDs to a lesser extent) induce cytochrome P450 3A4 and many other P450s.
Since half of all drugs are metabolized by 3A4, drug interactions with AEDs are very common and need to be considered if treating with an AED

Question 14

What happens to the metabolism of valproate and lamotrigine when they are given together?

Answer 14

Valproate competes with lamotrigine for a phase II enzyme, resulting in increased levels of lamotrigine because the body cannot eliminate it

Question 15

What AEDs are most likely to cause birth defects/teratogen?

Answer 15

phenytoin, carbamazepine, phenobarbital, valproate

Question 16

What AEDs are most likely to cause hypersensitivity reaction like Stevens-Johnson syndrome?

Answer 16

phenytoin, carbamazepine, phenobarbital, ethosoximide, lamotrigine

Question 17

What AEDs are most likely to cause cognitive slowing?

Answer 17

phenytoin, carbamazepine, phenobarbital, valproate, topiramate

Question 18

What AEDs are most likely to increase seizure activity or induce seizures?

Answer 18

phenytoin, tiagabine

Question 19

What kind of kinetics does phenytoin exhibit?

Answer 19

Somewhere in-between zero order and first order kinetics. This means that increasing the dose will result in a disproportionally large increase in plasma concentration
The kinetics of phenytoin vary widely from person to person

Question 20

Which AED is an inhibitor of CYP450s?

Answer 20

valproate

Question 21

What are the adverse effects of ALL AEDs?

Answer 21

suicidal thoughts and behaviors

Question 22

What are the adverse effects of phenytoin?

Answer 22

nystagmus and ataxia
megaloblastic anemia
hyperplastic gums
coarsening of facial features

Question 23

What are the adverse effects of phenobarbital?

Answer 23

megaloblastic anemia
may produce paradoxical excitatory effect in children
potential for abuse

Question 24

What are the adverse effects of valproate?

Answer 24

initially nausea, vomiting and anorexia but weight gain after chronic use
tremor
alopecia
thrombocytopenia
hepatotoxicity

Question 25

What are the adverse effects of carbamazepine and ethosuximide?

Answer 25

dizziness, diplopia
N/V
leukopenia and agranulocytosis

Question 26

What are the adverse effects of lamotrigine?

Answer 26

hypersensitivity reactions (e.g. Stevens-Johnson syndrome)
diplopia
Relatively free of adverse effects!

Question 27

What are the adverse effects of gabapentin?

Answer 27

weight gain

Question 28

Which AED has a completely renal elimination?

Answer 28

gabapentin

Question 29

What are the adverse effects of benzodiazapenes?

Answer 29

weight gain

Question 30

What AEDs are used for bipolar disorder?

Answer 30

valproate, carbamazepine and lamotrigine

Question 31

What AEDs are used for neuropathic pain?

Answer 31

carbamazepine - trigeminal neuralgia

gabapentin - post-herpetic neuralgia

Question 32

What AEDs are used for migraine prophylaxis?

Answer 32

topiramate, valproate

Question 33

What AEDs are used for alcoholism?

Answer 33

topiramate