S12) Anti-epileptic Drugs Flashcards
What is a seizure?
A seizure is an event of sudden excessive depolarisation/electrical activity in the neurones
What is epilepsy?
Epilepsy is a condition wherein a patient experiences more than one episode of unprovoked seizures
Distinguish between primary and secondary epilepsy
- Primary – idiopathic (no identifiable cause)
- Secondary – identifiable cause e.g. head injury, hypoxia, tumour, stroke, infection, hypoglycaemia, drugs
How does one classify seizures?
Describe some of the major recognised precipitants of epilepsy
- 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
What are the prescribing aims for a patient with epilepsy?
- 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
Why must anti-epileptic drugs be monitored during pregnancy?
- 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
What are the congenital abnormalities of using anti-epileptic drugs during preganancy?
- Neural tube defects
- Valproate syndrome
- Learning difficulties
Illustrate the effects of sodium valproate syndrome on an infant
What is the indication for benzodiazepines?
Benzodiazepines is a first line therapy for acute life threatening status epilepticus or any acute seizure that has not terminated in 5 mins
Provide some examples of benzodiazepines and when they are used respectively
- 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
In four steps, describe the mechanism of action of benzodiazepines
⇒ 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
Provide four examples of sodium channel blockers
- Sodium Valproate
- Lamotrigine
- Phenytoin
- Carbamazepine
In four steps, describe the mechanism of action of sodium channel blockers
⇒ 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
What is the indication for Sodium Valproate?
Sodium Valproate as first line therapy for primary generalised tonic–clonic seizures
Describe the possible drug interactions of Sodium Valproate
- Antidepressants – SSRIs, MAOIs, TCAs inhibit action of Valproate
- Antipsychotics – antagonise Valproate by lowering convulsive threshold
- Aspirin – competitive binding in plasma Valproate
Identify some adverse drug reactions of Sodium Valproate
- Most teratogenic (sodium valproate syndrome)
- Weight gain
- Hepatic function (40% elevated transaminases)
- Hepatic failure (rarely)
What is the indication for carbamazepine?
Carbamazepine as first line therapy for generalised tonic–clonic and all partial seizures
Describe the possible drug interactions of carbamazepine
- Decreases effect of many drugs – warfarin, OCP, steroids, phenytoin (strong CYP450 enzyme inducer)
- Contraindicated use with antidepressants
What are the adverse drug reactions of carbamazepine?
- General: dizziness, drowsy, ataxia, motor disturbance, numbness, tingling
- Rare: neutropenia
What is the indication for lamotrigine?
Lamotrigine can be used in either general/partial circumstances, and is probably the drug of choice for women of childbearing age (least teratogenic)
What is the indication for phenytoin?
- 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
Describe the possible drug interactions of phenytoin
Decreases the effect of many drugs – warfarin, OCP, steroids (CYP450 enzyme inducer)
What are the adverse drug reactions of phenytoin?
- Gingival hyperplasia (20%)
- Rashes – hypersensitivity → Stevens Johnson (2-5%)
In four steps, outline the process for emergency seizure management
⇒ 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)
