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
What are the adverse drug reactions of carbamazepine?
- General: dizziness, drowsy, ataxia, motor disturbance, numbness, tingling
- Rare: neutropenia
Iamotrigine moa
Na and Ca channel blocker
→ can cause aggression and agitation
→ phase 2 metabolism has a long half life
→ cont react with sodium valproate, phenytoin
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
→ it is 0 order and dependant on the blockage of Na channels
→ hard to manage
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%)
why is it relevant to know that phenytoin is zero order
→ zero order kinetics means rate of elimination is constant despite adding more drug = drug becomes toxic
→ it has a unpredictable half life so hard to predict drugs conc over time
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)
what are some examples of focal seizures
what are some examples of generalised seizures
classification of seizures
Prodrome
early signs or symptoms a seizure may be coming hours to days before
Aura
a “warning” – focal aware seizure leading to secondary generalised
Ictal
Interictal
- Ictal – during a seizure
- Interictal – between seizures often in reference to EEG
Post ictal
begins as seizure subsides – last minutes (to hours)
e.g. confusion, lack of consciousness, fatigue, headache, anxiety, frustration, embarrassment, muscle aching or pain, injury!
ldvdtiracetam
initiating and titrating doses
→ start at a low dose and gradually increase, aim is to be seizure free balanced with an acceptable amount of side effects
→ drug cons should be changed slowly by titration
what are some adverse effects of benzodiazepines
ataxia, depression, drowsiness, hypotension
what are some adverse effects of benzodiazepines
ataxia, depression, drowsiness, hypotension
order of treatment for epilepsy
What do AEDs split into
