NEURO - Anti-epilepsy

Question 1

Physiologically, how does seizures occur?

Answer 1

seizures occur when excitation (EPSP)&raquo_space; inhibition (IPSP); leads to repetitive and synchronous firing of APs

Question 2

What is the general principle of antiepileptic drugs in terms of GABA and glutamate?

Answer 2

GABA - inhibitory; most antiepileptics are GABA agonists

Glutamate - excitatory; most antiepileptics block glutamate release or act as glutamate receptor antagonists

Question 3

Antiepileptic Drugs that augment the IPSP effect of GABA: (3)

What is a general side effect of these drugs?

Answer 3

Barbituates (Phenobarbital)
Benzodiazepines (Lorazepam, Diazepam)
GABApentin

all causes sedation

Question 4

Antiepileptic Drugs that reduce the EPSP effect of Glutamate: (2)

Answer 4

Lamotrigine

Topiramate

Question 5

Antiepileptic Drugs that block Na channels: (5)

Answer 5

Phenytoin
Carbamazepine
Valproate
Lamotrigine
Topiramate

Question 6

Antiepileptic Drugs that block Ca channels (2)

Answer 6

Ethosuximide

Levetiracetam

Question 7

What is a common convergent pathway of seizures?

Answer 7

Na channels

Question 8

Antiepileptic drugs that block Na channels decrease AP firing of the neurons, thereby decreasing the seizure incidence. Why is it that AEDs do not induce a comatose state?

Answer 8

it does not bind to ALL VG Na channels

Question 9

How many half-lives does it take for AEDs to reach a steady state that is within the therapeutic range?

What would you do if an AED has a long half-life?

Answer 9

5

give the patient a loading dose to reach the therapeutic range rapidly

Question 10

What is the therapeutic index?

Answer 10

TI = TD50 / ED40

ED50 to be as LOW as possible
TD50 to be as HIGH as possible

Question 11

AEDs are metabolized through the _____ via the _____ and ____ enzymes

AEDs are excreted via: _____

Answer 11

metabolized: liver, via UDP glucouronyltransferase (UGT) and CYP2C9, C19, 3A4
excreted: renal

Question 12

Why is it that a person who is on carbamezpine should be careful when on concomitant treatment with

• erythromycin, fluconazole, valproate or Ca channel blockers?
• birth control?

Answer 12

Drugs: inhibit CYP enzymes, which increase CBZ concentrations

BC: CBZ induce metabolism of BC pills, thereby increasing the risk of pregnancy

Question 13

Describe 2 mechanism by which changes in AED metabolism can occur:

Give an example of each one.

Answer 13

1) auto-induction - CBZ induces its own metabolism and after a few weeks of therapy, levels tend to fall
2) polytherapy - AEDs can induce/inhibit metabolism of other AEDs. Example: Valproate raises the levels of lamotrigine.

Question 14

What is the AED drug of choice for pregnant women? Why?

What epileptic subtypes are these drugs best for?

Answer 14

Lamotrigine (blocks glutamate release and Na channels); causes few birth defects

Levitiracetam (blocks Ca channels)

both have broad spectrum efficacy against all seizure types

Question 15

What is a common side effect of AED in terms of:

allergic reactions?
GI effects?
CNS effects?

Answer 15

allergic reactions: rash
GI effects: nausea, diarrhea/constipation
CNS effects: sedating, fatigue

Question 16

Which AEDs are:

Weight neutral:
Weight gain:
Weight loss:

Answer 16

Weight neutral: phenytoin, lamotrigine, levetiracetam

Weight gain: carbamazepine, gabapentin, valproate

Weight loss: topiramate

Question 17

Which AEDs increase risk of polycystic ovarian syndrome (PCOS)?

Answer 17

Valproate
Carbamazepine

(if switched to lamotrigine, the risk decreases)

Question 18

Which AEDs have been implicated in osteoporosis?

Answer 18

phenytoin
Phenobarbital
Carbamazepine

Question 19

Which is easier to control: generalized epilepsy or focal epilepsy? Which one is more common?

Answer 19

easier to control: generalized

more common: focal

Question 20

Best drug to treat generalized epilepsy?

Best drug to treat focal epilepsy?

How do these affect weight?

How does this affect the polycystic ovarian syndrome (PCOS) risk?

What are alternative choices that are also good to treat both focal + generalized epilepsy?

Answer 20

Generalized: Valproate

Focal: Carbamazepine

Both cause weight GAIN and increase PCOS risk

Lamotrigine and Levetiracetam is a good alternate choice for both focal + generalized; both are weight NEUTRAL (also good for child-bearing women)

Question 21

Valproate is best for generalized seziures. What AED is good for secondarily generalized seizures?

Answer 21

GABApentin

Question 22

What AED is good for status epilepticus (when the brain is in a state of persistent seizure)?

Answer 22

Benzodiazepine (lorazepam, diazepam)

Question 23

What AED is good for all seizure types except absence seizures?

Answer 23

Barbituates (GABA agonist)

Topoiramate (glutamate receptor antagonist, GABA receptor agonist, Na channel blockade)