S12) Anti-epileptic Drugs

Question 1

What is a seizure?

Answer 1

A seizure is an event of sudden excessive depolarisation/electrical activity in the neurones

Question 2

What is epilepsy?

Answer 2

Epilepsy is a condition wherein a patient experiences more than one episode of unprovoked seizures

Question 3

Distinguish between primary and secondary epilepsy

Answer 3

• Primary – idiopathic (no identifiable cause)
• Secondary – identifiable cause e.g. head injury, hypoxia, tumour, stroke, infection, hypoglycaemia, drugs

Question 4

How does one classify seizures?

Answer 4

Question 5

Describe some of the major recognised precipitants of epilepsy

Answer 5

• Sensory stimuli e.g. flashing lights/strobes
• Brain disease / trauma e.g. brain injury, stroke, haemmorrhage
• Drugs/ Alcohol
• Metabolic disturbances e.g. hypoglycaemia/calcaemia/natraemia
• Infections e.g. febrile convulsions in infants

Question 6

What are the prescribing aims for a patient with epilepsy?

Answer 6

• Aim is for monotherapy – if one drug isn’t working despite increasing the dose, another should be tried
• Aim to start at a low dose and increase slowly – attempt to achieve seizure control at lowest possible dose to avoid side effects

Question 7

Why must anti-epileptic drugs be monitored during pregnancy?

Answer 7

• All anti-epileptic drugs are teratogenic
• One must weigh up risk to mum & baby of having a seizure during pregnancy due to poor control and birth defects

Question 8

What are the congenital abnormalities of using anti-epileptic drugs during preganancy?

Answer 8

• Neural tube defects
• Valproate syndrome
• Learning difficulties

Question 9

Illustrate the effects of sodium valproate syndrome on an infant

Answer 9

Question 10

What is the indication for benzodiazepines?

Answer 10

Benzodiazepines is a first line therapy for acute life threatening status epilepticus or any acute seizure that has not terminated in 5 mins

Question 11

Provide some examples of benzodiazepines and when they are used respectively

Answer 11

• Lorazepam – IV bolus 4mg is first line in emergency
• Midazolam – buccal if no IV access in emergency
• Diazepam – can be given rectally if no access

Question 12

In four steps, describe the mechanism of action of benzodiazepines

Answer 12

⇒ Enhancement of GABA action (inhibitory receptor in brain)

⇒ Results in increased Chloride current into neurone

⇒ Increases threshold for action potential generation

⇒ Decreases chance of reaching seizure threshold

Question 13

Provide four examples of sodium channel blockers

Answer 13

• Sodium Valproate
• Lamotrigine
• Phenytoin
• Carbamazepine

Question 14

In four steps, describe the mechanism of action of sodium channel blockers

Answer 14

⇒ Inhibition of voltage gated Na⁺ channel function by binding during depolarisation

⇒ Prolongs inactivation state (cannot stimulate another AP)

⇒ Reduces probability of high abnormal spiking activity (firing lots of action potentials)

⇒ VGSC blocker detaches once neurone membrane potential normalises

Question 15

What is the indication for Sodium Valproate?

Answer 15

Sodium Valproate as first line therapy for primary generalised tonic–clonic seizures

Question 16

Describe the possible drug interactions of Sodium Valproate

Answer 16

• Antidepressants – SSRIs, MAOIs, TCAs inhibit action of Valproate
• Antipsychotics – antagonise Valproate by lowering convulsive threshold
• Aspirin – competitive binding in plasma Valproate

Question 17

Identify some adverse drug reactions of Sodium Valproate

Answer 17

• Most teratogenic (sodium valproate syndrome)
• Weight gain
• Hepatic function (40% elevated transaminases)
• Hepatic failure (rarely)

Question 18

What is the indication for carbamazepine?

Answer 18

Carbamazepine as first line therapy for generalised tonic–clonic and all partial seizures

Question 19

Describe the possible drug interactions of carbamazepine

Answer 19

• Decreases effect of many drugs – warfarin, OCP, steroids, phenytoin (strong CYP450 enzyme inducer)
• Contraindicated use with antidepressants

Question 20

What are the adverse drug reactions of carbamazepine?

Answer 20

• General: dizziness, drowsy, ataxia, motor disturbance, numbness, tingling
• Rare: neutropenia

Question 21

What is the indication for lamotrigine?

Answer 21

Lamotrigine can be used in either general/partial circumstances, and is probably the drug of choice for women of childbearing age (least teratogenic)

Question 22

What is the indication for phenytoin?

Answer 22

• Phenytoin is a first line therapy for acute life threatening status epilepticus or any acute seizure (generalised tonic-clonic, all partial) that has not terminated after 10 mins
• It is used in emergency as a loading dose + infusion

Question 23

Describe the possible drug interactions of phenytoin

Answer 23

Decreases the effect of many drugs – warfarin, OCP, steroids (CYP450 enzyme inducer)

Question 24

What are the adverse drug reactions of phenytoin?

Answer 24

• Gingival hyperplasia (20%)
• Rashes – hypersensitivity → Stevens Johnson (2-5%)

Question 25

In four steps, outline the process for emergency seizure management

Answer 25

⇒ ABCDE approach

⇒ 4mg Lorazepam IV / 5mg diazepam PR

⇒If not terminating after 5 minutes, give further dose

⇒ If not terminating after 5-10 minutes, give IV phenytoin loading dose + infusion (call for help)