Anticonvulsant therapy Flashcards Preview

MBB Block II > Anticonvulsant therapy > Flashcards

Flashcards in Anticonvulsant therapy Deck (27):
1

What is kindling?

concept where repetitive subconvulsive stimuli can eventually induce convulsions, or even unprovoked seizures, via a "learning" process

2

What are some general mechanisms of epileptogenesis?

cellular: increased excitability, decreased inhibitory input, or changes in ion channels
Local/regional networks: alterned synaptic anatomy and physiology; bursing neurons entrain other neurons in a network that leads to regionalized spread and generalization (kindling)

3

What underlies primary generalized epilepsy?

excitatory thalamo-cortical activity usually has negative feedback from GABA-ergic neurons (specifically, nRT or thalamic reticular nucleus cells). The GABA-ergic neurons "know" when to fire based on when the glutaminergic neurons are firing b/c the glutaminergic neurons (and their targets!) all feedback onto the GABA neurons. columns of excitatory/inhibitory pairs are synchronized with each other. firing of these columns is the cause of spike-waves in epilepsy.

4

Why doesn't hypersynchrony occur all the time?

adjacent nRT neurons inhibit each other. Thus, these circuits' firing is usually slightly de-synchronized. If inhibitory connections between nRT (GABA-ergic neurons) are lost, then the brain is primed for synchronice firing and epilepsy

5

Typical Na channel blocking drugs. Typical action.

phenytoin, carbamazepine (and oxcarbazepine), lamotrigine (these 3 are the prototypes); topiramte, zonisamide (have additional activities)
Also maybe valproate?
Most act by stabilizing the inactivated state of the Na channel to limit sustained repetitive firing

6

What are the 2 new Na channel binding drugs and how do they work?

rufinamide and lacosamide. stabilize Na channels- lead to slow inactivation.

7

What kinds of drugs enhance GABA-A mediated inhibition?

barbiturates, benzodiazepines, tiagabine
(topiramate- weak effect, vigabatrin, gabapentin?)

8

How do gabapentin, vigabatrin, and tiagabine work?

increase effects of GABA-A mediated inhibition by increasing GABA release or decreasing GABA reuptake

9

How does vigabatrin work?

increase effects of GABA-A mediated inhibition by decreasing the breakdown of GABA-A receptors

10

What drugs block glutamate receptors?

felbamate and topiramate

11

What is felbamate? How does it work and what should I know about its use?

acts at NMDA receptors to block glutamate activation
Can also block glycine
But, felbamate can cause aplastic anemia and lead to patient death in ways that are UNPREDICABLE and thus UNPREVENTABLE. Very difficult consent involved with this drug. Use only as last line before brain surgery.

12

What does topiramate do?

Na, AMPA (glutamate channel), and GABA-A channel effects

13

What drugs block Ca channels and how do they work?

Ethosuximide, valproate, and zonisamide, gabapentin
block T-type Ca channels (that open after hyperpolarization) to interrupt oscillatory thalamo-cortical activation. Especially good for childhood absence seizures.

14

What drugs enhance K channels?

enhance K channels, since these channels repolarize the cell
Ezogabine/retigavine (Potiga)

15

Side effects of ezogabine/retigavine?

blue skin
retinopathy

16

What does primidone do and how does it work?

Primidone reduces sustained repetitive firing. But, its metabolites (phenobarbital and PEMA) enhance GABA action

17

How does zonisamide work?

action on Na and Ca channels

18

How does valproate work?

action on Na, Ca channels; maybe GABA?

19

Benzodiazepines vs. barbiturates

benzos: increase GABA-A receptor affinity for GABA
barbiturates: increase duration of channel opening following GABA binding

20

What is a key limitation of gabapentin?

absorption is a challenge; you are limited by l-amino acid transporters. careful about food. Also, the more gabapentin you give, the smaller the proportion of it that is absorbed

21

What drugs are strong protein binders? Moderate?

pheytoin, valproate (strong)
(moderate are carbamazepine and lamotrigine)

22

What is the most important drug-drug interation with seizure meds?

valproate increases the risk of LAMOTRIGINE-INDUCED STEVENS JOHNSONS RASH and DEATH

23

Main metabolism of anti-seizure drugs? What are inducers?

mostly CYP450. UDP glucuronyl transferase also important.
Carbamazepine, barbiturates, phenytoin and topiramate.
Carbamazepine + OCPs = PROBLEM- increased OCP degradation can lead to ACCIDENTAL PREGNANCY

24

What are causes of non-linear kinetics for seizure drugs?

gabapentin: absorption differences
valproate: distribution diffs
phenytoin: metabolism diffs

25

What should I know about seizures and menstruation?

catemenial seizures: associated with menstruation. Estrogen is pro-seizure; progesterone is anti-seizure. We see seizures most during menstruation (high estrogen/progesterone ratio) and during months without ovulation (low progesterone)

26

What should I know about seizure and pregnancy?

valproate increases birth defects 7 fold as well as persistant lower IQ levels for the child
lamotrigine and carbamazepine are relatively safe

27

What drugs are most dangerous for bone health?

phenytoin, primidone, and phenobarbital.