S12.1 Anti-epileptic Drugs

Question 1

Define seizure

Answer 1

Sudden excessive electrical activity in neurones

Question 2

Define epilepsy

Answer 2

More than one unprovoked seizure episodes

Question 3

What is the difference between partial and generalised seizures?

Answer 3

Partial seizures – Symptoms reflect area affected.

Generalised seizures – Generated centrally, spread through both hemispheres with loss of consciousness.

Question 4

What are the primary and secondary causes of seizures?

Answer 4

Primary = idiopathic
Secondary = identifiable cause e.g. brain injury, stroke, tumour

Question 5

What are the two classes of anti-epileptic drugs?

Answer 5

VG Sodium Channel Blockers

Drugs Enhancing GABA Mediated Inhibition

Question 6

What is the mechanism of VG Sodium Channel Blockers?

Answer 6

Inhibition of VGSC by binding to the internal face. This prolongs their inactivation state, so can’t stimulate another AP. Also reduces probability of high abnormal spiking activity

Question 7

Describe the uses and pharmacokinetics of carbamazepine

Answer 7

Used to treat generalised tonic-clonic and all partial seizures.
PK: Strong CYP450 enzyme inducer, so initial t1/2 is 30hrs yet with repeated use, the t1/2 becomes 15hrs

Question 8

Describe the ADRs and DDIs of carbamazepine

Answer 8

ADRs: dizziness, vomiting, variable BP
DDIs: CYP450 inducer so decreases the effect of many drugs e.g warfarin, corticosteroids, oral contraceptives

Question 9

Describe the uses and pharmacokinetics of phenytoin

Answer 9

Used to treat generalised tonic-clonic and all partial seizures.
PK: CYP450 inducer. Non-linear PK at therapeutic levels so close dose monitoring required.

Question 10

Describe the ADRs and DDIs of phenytoin

Answer 10

ADRs: gingival hyperplasia, hypersensitivity rashes
DDIs: competitive binding with Valproate to increase levels, reduce oral contraceptive effect

Question 11

Describe the uses and pharmacokinetics of lamotrigine

Answer 11

Used to treat generalised tonic-clonic, all partial and absence seizures
PK: No CYP450 induction so fewer DDIs

Question 12

Describe the ADRs and DDIs of lamotrigine

Answer 12

ADRs: some CNS (e.g dizziness), mild rashes
DDIs: adjunct therapy with other AEDs, oral contraceptives reduce its levels, and valproate increases levels

Question 13

Describe the mechanism of drugs enhancing GABA Mediated Inhibition

Answer 13

GABA is one of main inhibitory receptors in brain. Increased GABA results in increased Cl- current into neurones through Cl channel – this increases threshold for ap generation

Question 14

Describe the uses and mechanism of sodium valproate

Answer 14

Used to treat primary generalised tonic-clonic seizures.
Increases GABA content of the brain by stimulating GABA synthesising enzymes and inhibiting GABA inactivating enzymes

Question 15

Describe the ADRs and DDIs of sodium valproate

Answer 15

ADRs: teratogenic, weight gain
DDIs: Antidepressants inhibit action of Valproate,
Antipsychotics antagonise Valproate by lowering convulsive threshold.

Question 16

Describe the uses and mechanism of benzodiazepines?

Answer 16

Lorazepam and diazepam (for status epilepticus), midazolam (absence seizure).
Act at a distinct receptor site on GABA Chloride channel; this enhances GABA action

Question 17

Describe the ADRs and DDIs of benzodiazepines

Answer 17

ADRs: sedation, confusion, aggression
DDIs: some adjunctive use

Question 18

Describe the uses and mechanism of Ethosuximide

Answer 18

Used in absence and general seizures

Mechanism: Prevent depolarisation causing “spike and wave” discharge

Question 19

What is the mechanism of Levetiracetam?

Answer 19

Binds to synaptic vesicles to inhibit pre-synaptic calcium channel activity, therefore inhibiting neurotransmitter release

Question 20

Summarise what drug is best to use for each type of seizure

Answer 20

Sodium Valproate for primary generalized seizures.
Carbamazepine as for partial seizures.
Lamotrigine for either, esp for women of childbearing age as least teratogenic.
Benzodiazepines and phenytoin for acute life threatening status epilepticus.

Question 21

What congenital abnormalities can sodium valproate cause?

Answer 21

Neural tube defects, learning difficulties, facial/digit hypoplasia.

Question 22

What are the management steps for status epilepticus?

Answer 22

First ABCDE approach, check blood glucose, U+Es.
Give benzodiazepines – IV lorazepam.
If seizure not terminating (5 min) give further dose.
If still not terminating (10 min) give phenytoin and call ITU.