Anti-Epileptic Drugs

Question 1

Epilepsy can be classified into which two main types?

Answer 1

Partial seizures

Generalised seizures

Question 2

What is another name for partial seizures?

Answer 2

Focal seizures

Question 3

Partial seizures can be sub-divided into what categories?

What is the difference between the two?

Answer 3

Simple (conscious)

Complex (impaired consciousness)

Question 4

During a focal seizure, symptoms reflect what?

Answer 4

The area affected by the seizure

Including involuntary motor disturbance, behavious change

Question 5

Generalised seizures can be subdivided into which types?

How do these types differ

Answer 5

Tonic-clonic seizure: rigidity followed by muscle contraction

Absence seizure: no shaking, unable to respond to stimuli

Question 6

What is status epilepticus?

Answer 6

A prolonged seizure beyond 5 minutes or as a series of seizures without any recovery interval

Question 7

List some of the dangers associated with severe epilepsy

Answer 7

Injury relating to fall/crash

Hypoxia

Sudden death in epilepsy

Question 8

What is the difference between primary and secondary epilepsy?

Answer 8

Primary: no identifiable cause (idiopathic)

Secondary: caused by another medical condiiton e.g. vascular disease, tumour

Question 9

List some precipitating factors of epilepsy

Answer 9

Sensory stimuli: flashing lights

Brain disease/Trauma: head injury, stroke, drugs, lesion

Metabolic disturbance: Hypo-glycaemia,calcaemia,natraemia

Infections: febrile convulsions in infants

Therapeutics: AEDs + polypharma

Question 10

What are the two established therapeutic targets for anti-epileptic drugs?

Answer 10

Voltage-gated sodium channel blockers

Enhanced GABA-mediated inhibition

Question 11

Where do volatage gated sodium channel blockers bind to elicit their effect?

Answer 11

The inside of the membrane, on domain 1V

Question 12

Briefly explain the mechanism of VGSC blockers in the treatment of epilepsy

Answer 12

VGSc blockers access the binding site during depolarisation- making it voltage dependent

This prolongs the inactivated state

Firing rate returns to normal

Question 13

VGSCs have three states, what are they?

At which stage to VGSC blockers act?

Answer 13

1. Open (resting)
2. Closed (activated)
3. Inactivated (closed to Na+ via inactivation gate)

Question 14

What does Carbamezepine work?

Answer 14

It prolongs VGSC inactivation state to allow the firing rate to go back to normal

Question 15

List some adverse drug reactions of carbemazepine

Answer 15

CNS effects: dizziness, drowsiness, ataxia, numbness, tingling

GI effects: vomiting

CVS: variation in BP

Question 16

What feature of carbamezepine means that it can effect other drugs?

Answer 16

It is a strong inducer of CYP450

Question 17

Which seiure types may be treated with carbamezepine?

Answer 17

All partial

Generalised: Tonic-clonic

Not: absence

Question 18

At therapeutic levels, what pharmacokinetics does Phenytoin display?

What does this mean for its use clinically?

Answer 18

Non-linear

Has a very variable half life (6-24 hours)

Means that therapeutic dose is very variable

Question 19

List some ADRs of Pheytoin

Answer 19

CNS: dizziness, headache, nervousness

Gingival hyperplasia (20%)

Rashes, hypersensitivity

Question 20

What kind of monitoring is involved in the use of Phenytoin?

Answer 20

Monitoring of free concentration in plasma

Question 21

Which type of seizure can be treated with Pheytoin?

Answer 21

Generalised tonic-clonic

All: partial seizures

NOT: absence seizures

Question 22

Why is Lamotrigine increasingly being used as a first line drug, over Pheytoin and Carbamezepine, for the treatment of epilepsy?

Answer 22

It is well absorbed

It displays linear pharmacokinetics

Fewer ADRs and DDIs

May be safer in pregnancy

Question 23

Which seizures can Lamotrigine be used to treat?

Answer 23

Partial seizures

Generalised: tonic-clonic AND absence seizures

+other subtypes

Question 24

What is the general mechanism of GABA mediated inhibition of excitatory neurones?

Answer 24

GABA (or GABA agonist) binding increases the Cl- current into the neurone

This increases the threshold for AP generation

Making it harder for AP to be generated

Question 25

What is Valporate's mechanism of action?

Answer 25

1) It is a weak inhibitor of GABA inactivation enzymes and a weak activatory of GABA synthesising enymes which both lead to increased GABA 2) It is a VGSC blocker and a weak Ca2+ blocker- both of which decrease discharge firing

Question 26

What kind of pharmacokinetics does Valporate display? What is its half life?

Answer 26

Linear kinetics Half life: 15 hours

Question 27

What drug monitoring is required in patients that are treated with Valporate?

Answer 27

Monitor free plasma concentration- though this does not correlate well with efficacy Blood, hepatic and metabolic function should be monitored

Question 28

What types of epilepsy can be treated with Valporate?

Answer 28

Partial seizures Generalised: tonic-clonic AND absence seizures

Question 29

What is the mechanism of action of Benzodiazepines?

Answer 29

They are positive allosteric effectors of GABA receptors Act on GABA receptor to increase Cl- current into neurone Increases the threshold for AP generation Harder to generate AP

Question 30

List some adverse drug reactions of Benzodiazepines

Answer 30

Sedation Tolerance with chronic use Respiratory/CNS depression

Question 31

Which epilepsy types can be treated using Benzodiazepines?

Answer 31

Status epilepeticus- only SHORT-term Absence seizure- only SHORT-term

Question 32

What are some importants things to consider when using anti-epileptic drugs during pregnancy?

Answer 32

To consider each patient individually Take stage of pregnancy into account Balance the risk of treatment with the risk of harm due to seizure

Question 33

Valporate poses the risk of what if used during pregnancy?

Answer 33

Neural tube defects

Question 34

The use of multiple AEDs during pregnancy is associated with an increased risk of what?

Answer 34

Tetatogenicity

Question 35

Which dietary supplementation can be taken by women taking AEDs to reduce the risk of neural tube defects in the baby?

Answer 35

Folate

Question 36

Which dietary supplementation can be taken by women taking AEDs to reduce the risk of coagulopathy and cerebral haemorrhage in the baby?

Answer 36

Vitamin K

Question 37

What are the main priorities when dealing with a patient with status epilepticus?

Answer 37

ABCDE Exclusion of hypoglycaemia High AED doses may result in hypoventilation ITU may be required: paralysis and ventilation