S12) Anti-epileptic Drugs Flashcards
What is a seizure?
A seizure is an event of sudden excessive depolarisation/electrical activity in the neurones → sudden and temporary
(not everyone who has seizures has epilepsy)
what other conditions can present with similar features to epilepsy
→ vasovagal syncope
→ cardiac arrhythmia
→ panic attacks or hyper ventilation
→ TIA
What is epilepsy?
Epilepsy is a condition wherein a patient experiences more than one episode of unprovoked seizures
→ prevalence increases with age
what are some differential diagnosis of children with epilepsy
→ febrile convulsions
→ breath holding attacks
Distinguish between primary and secondary epilepsy
- Primary – idiopathic (no identifiable cause)
- Secondary – identifiable cause e.g. head injury, hypoxia, tumour, stroke, infection, hypoglycaemia, drugs
what are some risk factors of epilepsy
→ premature birth
→ genetic conditions
→ cerebrovascular disease
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
how do you make a diagnosis
→ urget referral after first seizure
→ asses risk of second seizure
→ info on how to recognise seizure
MRI, ECG
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)
- thrombocytopenia
- Weight gain
- Hepatic function (40% elevated transaminases)
- Hepatic failure (rarely)
what is the mechanism of action of Carbamazepine
→ use-dependant blockage of Na channels and reduced Ca influx and reduced glutamate
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
