11.1 Antiepileptic Drugs

Question 1

What is the mechanism of action of carbamazepine, phenytoin and lamotrigine?

Answer 1

Block voltage gated sodium channels
Prolongs the inactivation State
So they prevent proliferation of APs

Only bind to channels that are open, hence why they are voltage dependent

Question 2

Which antiepileptic medications cannot be used for absence seizures?

Answer 2

Phenytoin and carbamazepine

Question 3

How do carbamazepine and phenytoin affect CYP450?

Answer 3

Strong CYP450 inducers

Question 4

Why does phenytoin have many drug interactions?

Answer 4

As it is very highly protein bound

Competitive binding e.g. with NSAIDS, valproate

Question 5

Why does lamotrigine have fewer drug interactions than other VGSC blocker anti epileptics?

Answer 5

As it is not a CYP450 inducer

Question 6

What are some side effects of phenytoin?

Answer 6

Headaches
Nystagmus
Dizziness
Teratogenic (cleft lip and palate)
Confusion
Vertigo

Question 7

What are some side effects of carbamazepine?

Answer 7

Dizziness
Drowsiness
Ataxia
Motor disturbance
GI upset
Water retention and hyponatraemia
Skin rash

Question 8

Why is the therapeutic window of phenytoin so narrow?

Answer 8

As it has non linear pharmacokinetics

This is exacerbated by other drugs that competitively bind at proteins and displace it, so increasing its plasma levels

Question 9

Which antiepileptic medication is safest in pregnancy?

Answer 9

Lamotrigine

Question 10

Why is lamotrigine an increasingly favoured antiepileptic drug?

Answer 10

Linear pharmacokinetics 
No CYP450 inductions so fewer DDIs
Less marked ADRs
Can use in pregnancy 
Adjunct therapy with other anti epileptic drugs

Question 11

How does sodium valproate affects plasma levels of lamotrigine?

Answer 11

Increases plasma levels of lamotrigine due to competitive binding

Question 12

What electrolyte does GABA increase the uptake of into a neurone?

Answer 12

Increases uptake of chloride ions
Which makes the membrane potential more negative
And so increase the threshold for AP generation

Question 13

What is the mechanism of action of sodium valproate?

Answer 13

Enhances GABA activity post synaptically (by inhibiting enzymes that breaks down GABA, and stimulating enzymes that synthesis GABA)
Also a sodium channel inhibitor

Question 14

What affect can sodium valproate have during pregnancy?

Answer 14

Very teratogenic
Neural tube defects
Facial and digit hypoplasia

Question 15

How does anti epileptic medication affect a px on an OCP?

Answer 15

Carbamazepine and phenytoin are CYP450 inducers
So the metabolism of the OCP is increased
So OCP dose would need to be increased, or another method of contraception used

Question 16

What are some side effects of sodium valproate?

Answer 16

Generally less severe than with other anti epileptic drugs
(Other than teratogenicity)

Thinning and curling of hair
Sedation
Weight gain
Hepatotoxcitiy (can increase transaminase)

Question 17

How do benzodiazepines work?

Answer 17

Act on GABA chloride channel to increase chloride influx to make membrane potential more negative and increase the threshold for AP generation

Question 18

When at benzodiazepines indicated?

Answer 18

Lots of ADRs so only use in status epilepticus

Question 19

What are some side effects of benzodiazepines?

Answer 19

Sedation
Confusion
Aggression
Tolerance
Dependence
Respiratory and CNS depression
Abrupt withdrawal can trigger seizure

Question 20

How do antidepressants affect sodium valproate?

Answer 20

Inhibit the action of sodium valproate

Question 21

In status epilepticus, why is lorazepam preferred to diazepam?

Answer 21

Longer half life

Question 22

How would you managed a px with status epilepticus?

Answer 22

ABCDE
Exclude hypoglycaemia
IV/ PR lorazepam (can given again after 5 minutes if necessary)
If no change, phenytoin IV (but careful cardiac monitoring to avoid arrhythmias)