Anti-epileptic drugs

Question 1

What are the two main classes of AEDs?

Answer 1

Voltage gated sodium channel blockersGABA mediated inhibition

Question 2

Give some drugs which are voltages gated sodium channel blockers

Answer 2

PhenytoinLamotrigineCarbamazepine

Question 3

Give some drugs which involve GABA mediated inhibition

Answer 3

BenzodiazepinesSodium valproate

Question 4

What is the general action of VGSC antagonists?

Answer 4

Bind to a depolarised Na channel and prolong the inactivated state, to decrease the probability of high abnormal spiking activity. It will detach when the AP is back to normal

Question 5

What is the general action of GABA mediated inhibition?

Answer 5

Drug binds to Cl channel and shows positive allosteric modulation. This increases the receptors affinity for GABA. GABA acts by causing an influx of Cl- into the cell, which increases the threshold for an action potential generation. This causes a reduction in the likelihood of epileptic neuronal hyperactivity.

Question 6

Give some characteristics of phenytoin

Answer 6

CYP inducer - warfarin, OCPCimetidine increases conc of phenytoin90% protein bound, competitive binding1st order kinetics at therapeutic levels, so need close monitoring of plasma levels. Reaches therapeutic levels very quickly.

Question 7

Give some characteristics of carbamazepine

Answer 7

Don’t use in absence seizuresCYP inducerProtein boundAntidepressants interfere with actionInitially has a long t1/2, but gets shorter with long term use. From 30 down to 15.

Question 8

Give some characteristics of lamotrigine

Answer 8

OCP - reduces lamotrigine levelsValproate increases lamotrigine levelsAppears to be safer in pregnancy than others

Question 9

Give the mechanism of action for sodium valproate

Answer 9

Weak inhib. of GABA inactivation enzymesWeak stimulus of GABA synthesising enzymesWeak VGSC blocker (decrease discharge)Weak Ca2+ channel blocker (decrease discharge)

Question 10

Give some characteristics of sodium valproate

Answer 10

Antidepressants inhibitAntipsychotic antagoniseAspirin diplaces, increase plasma conc. Linear PK

Question 11

Give some characteristics of benzodiazepines

Answer 11

Highly protein boundIV flumazenil can reverse an overdose.

Question 12

Give some teratogenic effects that AEDs can have

Answer 12

Neural tube defectsFacial and digit hypoplasiaLearning difficulties and mild neurological dysfunctionVitamin K deficiency (decreased production of clotting factors, haemmorhagic disease of the newborn)Risk of birth defects increases from 2% to 8%

Question 13

What are the failure rates of the OCP with AEDs?

Answer 13

Increases from 1-2% to 5-10% with carpamazepine and phenytoin

Question 14

What is the therapeutic range of phenytoin?

Answer 14

40-100 micro moles- need to have plasma conc monitoring - very narrow therapeutic range- 1st order PK, so can get to toxic levels very quickly- PK depend on each patient- can measure saliva levels

Question 15

What do you need to watch for when you give phenytoin for status epilepticus?

Answer 15

HypotensionCardiac arrhythmias

Question 16

Give the ADRs of phenytoin

Answer 16

DizzinessAtaxiaNystsgmusGingivival hyperplasiaRashes

Question 17

ADRs of carbamazepine

Answer 17

DizzinessDrowsinessAtaxiaMotor disturbancesBP changesHyponatremiaRashesMyelosuppression

Question 18

ADRs of lamotragine

Answer 18

DizzinessAtaxiaDrowsinessNauseaSkin rashes- can be serious, so not used in kids

Question 19

ADRs of sodium valproate

Answer 19

Less severe than other AEDsCNS sedation - ataxia and tremorWeight gainHepatic dysfunctionHepatic failure

Question 20

ADRs of benzodiazepines

Answer 20

Sedation ToleranceWithdrawal/dependenceAggressionConfusionAbrupt withdrawal can be a seizure triggerRespiratory and CNS depression