12 - Epilepsy Flashcards
What is a seizure?
Transient occurencer of signs or symptoms due to abnormal electrical activity in the brain leading to a disturbance of consciousness, behaviour, emotion, motor function or sensation
What is the pathophysiology of a seizure?
- Abnormal excessive excitation and synchronisation of a group of neurones in the brain
- This can be due to a loss of inhibitory signals (GABA) OR and excess of excitatory signals (Glutamate)
What are some causes of seizures?
- Genetic epilepsy syndromes (genetic differences in receptor structure)
- Exogenous activation of receptors e.g drugs and alcohol
- Changes in brain chemistry e.g drug withdrawal, metabolic changes like low glucose
- Damage to any networks e.g stroke or tumour knocking out inhibitory neurones
What are some signs and symptoms of seizures?
- Generalised have loss of consciousness, changes in muscle tone, tongue biting
- Tonic clonic have initial hypertonic phase then rapid clonus
- Post-ictal period
- Often aura before
What is the definition of epilepsy and what is the criteria that has to be met to fulfil this diagnosis?
- Tendency towards recurrent seizures unprovoked by a systemic or neurological insult. Due to abnormal hyperactivity in the brain
- At least 2 unprovoked (or reflex) seizures occuring more than 24 hours apart OR one unprovoked seizurte and a high recurrence risk (60% over 10 years)
What is a reflex seizure?
How can we classify seizures?
- Generalised: electrical spread across both hemispheres of the brain and result in a loss of consciousness. Absence and tonic-clonic seizures
Focal Onset: no loss of awareness mostly and the most common type of seizure
What are provoked seizures and how do we treat them?
- Seizure as a result of another medical condition
- Need to treat both the seizure and the underlying condition and unlikely to need ongoing AED treatment if cause treated
What are some differential diagnoses for seizures?
Pseudoseizures are a result of psychological causes such as severe mental stress, they won’t response to benzodiazepenes
What is the initial management for a seizure?
- Primary Survey
- Start a timer
- Get some help
- Wait five minutes before giving drugs as most self-terminate
What is status epilepticus?
- Medical emergency as the brain uses up all of its resources and hypoxia occurs. Can lead to sudden death months later due to effects on brain
- Can also lead to AKI due to rhabdomyolysis from muscle contractions
What is the pharmacological treatment pathway for status epilepticus?
- Wait five mins with A to E
- Benzodiazepines (Lorazepam IV)
- Benzodiazepines again
- Phenytoin Infusion
- Thiopentone/Anaesthesia but call ICU
Only take next step if not resolving
How do benzodiazepenes work in epilepsy?
GABA enhancing drug so cause cells to become hyperpolarised with Cl- ions so less likely to fire
- Lorazempam (IV): Fast acting
- Diazepam (rectally)
- Midazolam (buccal): middle acting
Put in slowly as can always add more
What investigations do clinicians do into seizures to see whether there is a diagnosis of epilepsy/which type of epilepsy a patient has?
- Ask for eyewitness accounts of seizures or videos
- EEG sleep deprived but sometimes shows no abnormalities or normal people have abnormal EEG
- MRI to rule out vascular or structual epilepsy
- FBC to check ion levels e.g Mg and Ca
Why do we give patients with epilepsy anti-epileptic drugs?
- Sudden Unexplained Death in Epilepsy risk higher in people with poor seizure control
- Massive impact on life: cannot drive, swim, have a bath, time out of work and school
How do the main AEDs we use work?
- Many drugs work in several ways e.g valproate
- Na Channel Blockers: Carbamazepine, Lamotrigine, Phenytoin
How does carbamazepine work as an AED and what are the side effects and DDIs of this drug?
- Block Na channels in central neurones so slows recovery of inactive neurones to closed neurones, reducing neuronal transmission
ADRs: Suicidal thoughts, joint pain, bone marrow failure, dizziness, rashes
DDIs: shortens own half life so dose needs to be altered long term as CYP inducer, lowers effect of warfarin, OC pill, phenytoin
- Also used to treat bipolar and chronic pain
How do voltage gated sodium channel blockers act as AEDs?
Bind to channel during depolarisation to prolong the inactive state of the neurone, once the membrane potential goes back to normal the drug detaches
e.g valproate, carbamazepine and phenytoin
What are the side effects and DDIs of phenytoin?
- Na channel blocker
Side effects: bone marrow suppression, hypotension, arrhythmias when used IV, gum hyperplasia
DDIs: CYP induce so decrease OC effectiveness, highly bound to plasma proteins so when take NSAIDs higher plasma conc as displaces, zero order kinetics so be careful with dose
What AEDs are used for each classification of epilepsy?
- Lamotrigine: focal or generalised when valproate cannot be used. Can be used for absence due to actions on Ca channels
- Valproate: generalised
- Carbamazepine and Phenytoin: all but absence
What are the side effects and DDIs of sodium valproate?
- GABA enhancing drug by indirectly increasing GABA synthesis and Na blocker
- Side effects: liver failure, pancreatitis, lethargy, weight gain, ataxic tremor
- ADRs: SSRis and antipsychotics lower valproate levels but aspirin increases it
What are the side effects and DDIs of lamotrigine?
- VGSC blocker but also Ca channel blocker
- Safer in pregnancy
- Lowers OC pill effectiveness
What is the MOA of levetiracetam?
Synaptic vesicle glycoprotein binder preventing Ca influx in the presynaptic knob so neurotransmitter cannot be released
Used for focal and generalised seizures
Safe in pregnancy
What are some side effects of AEDs in general?
- Tiredness/Drowsiness as stopping neuronal transmission
- Nausea and Vomiting
- Mood changes and suicial ideation
- Osteoporosis
- Steven Johnson syndrome (mostly phenytoin and carbamazepine)
- Anaemia, thrombocytopenia and bone marrow failure
REGULAR FBCs NEEDED
What effect do the AEDs have on CYP450 enzymes?
How do you start someone on AEDs and how would you transition the from one drug to another?
- Pick a drug and start low dose and work up
- Check for tolerable side effects and want to be seizure free
- Can monitor plasma levels but only if neccessary e.g pregnancy or issues with adherance or increase seizure frequency
- If starting another drug titrate first down and titrate second up
What advice needs to be given to young women on AEDs?
- Should be enrolled in pregnancy prevention programme if on valproate as 10% change of congenital malformation
- Lamotrigine and Levetiracetam are the safest
Complete the following table.
What is unusual about carbamazepines interaction with CYP450 enzymes?
Induces its own metabolism so dose has to be altered when given long term
When is midazolam useful over lorazepam?
When you cannot get IV access in a child, can give buccally or intranasally
Define:
- Prodrome
- Aura
- Ictal
- Interictal
- Post ictal
