Session 13 Epilepsy Flashcards
What is the definition of a seizure?
TRANSIENT occurrence 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 are the differences between glutamate/NMDA receptor and the GABA receptors in terms of depolarisation and action potential firing?
Glutamate = depolarises membrane and more likely to fire action potential
Gaba = hyper polarises membrane and less likely to fire action potential
What is a seizure a clinical manifestation of?
Abnormal and excessive excitation and synchronisation of a group of neurones within the brain
Describe the pathology of seizures i.e. what actually happens to cause it
Loss of inhibitory - GABA mediated - signals
OR
Too strong excitatory - NMDA / glutamate - signals
This imbalance can happen in any pint in the brain and local changes can lead to generalised effects
what can there imbalance of signals in the brain be caused by?
Genetic differences in brain chemistry / receptor structure = genetic epilepsy syndrome
Exogenous activation of receptors = drugs
Acquired changes in brain chemistry = drug withdrawal and metabolic changes
Damage to any of the networks = strokes and tumours
What are some of the symptoms and signs of seizures?
Generalised seizures = loss of consciousness with changes in muscle tone, tongue biting
Tonic-clonic = hypertonic phase followed by rapid clonus (shaking and jerking)
A post-ictal period - which can last minutes to hours
= an altered state of consciousness that is characterised by drowsiness, confusion, nausea hypertension
Aura prior to seizure
Varied and subtle depending on type of seizure
Define epilepsy
Plus the diagnostic criteria to diagnose epilepsy
Epilepsy = a tendency toward recurrent seizes unprovoked by a systemic or neurological insult
Diagnosing epilepsy syndrome;
At least two unprovoked (or reflex) seizures occurring more than 24 hours apart
One unprovoked seizure and a probability of further seizures similar to the general recurrence risk after two unprovoked seizures
What is a reflex seizure?
Seizure brought on by a particular stimulus
What are some stimuli that can cause a reflex seizure?
Photogenic Musicogenic Thinking Eating Hot water immersion Reading Orgasm Movement
Where do generalised seizure originate at?
Some point within and rapidly engage bilaterally distributed networks
Can include cortical and subcortical structures but not necessarily the entire cortex
Where do focal seizures originate from?
Within networks limited to one hemisphere
My be discretely localised or more widely distributed
Grand mal =
Petit mal =
Partial seizure =
Grand mal = generalised seizure
Petit mal = absence seizure
Partial seizure = focal seizure
What are provoked seizures and when might they occur?
Seizure as a result of another medical condition
From
Drug use or withdrawal
Alcohol withdrawal
Head trauma and intracranial bleeding
Metabolic disturbances - hyponatraemia, hypoglycaemia
CNS infections - meningitis and encephalitis
Febrile seizures in infants
Uncontrolled hypertension
What is status epilepticus?
A seizure (of any variety) lasting 5 minutes or more, or multiple seizures without a complete recovery between them
Medical emergency status
Pharmacological treatment for status epilepticus
Wait 5 minutes Benzodiazepine Benzodiazepines again Phenytoin Thiopentone / anaesthesia
Always look at the time!
What drug class are benzodiazepines?
GABAa agonists
all end in -apam
How do benzodiazepines work?
Increased Cl- conductance so there is a more negative resting potential - less likely to fire
Work best when membrane positive (in seizures)
Warnings of benzodiazepine use?
Addiction
Cardiovascular collapse
Airway issues
In addition to seizure treatment, what are benzodiazepines also used for?
Anxiolytics
Sleep aids
Alcohol withdrawal
What investigations would you do when investigating a seizure/ epilepsy?
Electroencephalography
MRI
Video the seizure!
Which AED’s MOA is sodium channel blockage (fast inactivation)
Phenytoin
Carbamazepine
Valproate
How do sodium channel blockade AED’S work?
Blocking of sodium channels in central neurones
Slows recovery of neurones from inactive to closed state
Reduces neuronal transmission
Carbamazepine
MoA
Also used for?
Side effects?
Sodium channel blocker
Also used for
* bipolar and chronic pain n
Side effects:
- suicidal thoughts
- joint pain
- bone marrow failure
Phenytoin
MoA
Used mainly in…
Specific side effects …
Sodium channel blocker
Used mainly in …
* status epilepticus or as an adjunct in generalised seizures
Exhibits zero order kinetics so need to take care when adjusting dose
Side effects
- bone marrow suppression
- hypotension
- arrhythmias (IV use) the
Sodium valproate
MoA
Specific side effects
Mix of GABAa effects and sodium channel blockage
Specific side effects
- liver failure
- pancreatitis
- lethargy
lamotrigine
Type of drug
Good for?
Used when?
Primarily a sodium channel blocker, may los affect calcium channels
Good for focal epilepsy
Used often where valproate contraindicated in generalised epilepsy
Levetiracetam
MoA?
Used in?
Synaptic vesicles glycoprotein binder - stops the release of neurotransmitters into synapse an reduces neuronal activity
Option for focal seizures and generalised seizures
Safe in pregnancy
General side effects of AEDs?
Tiredness and drowsiness
N and V
Mood changes and suicidal ideation
Osteoporosis
Rashes - most likely in carbamazepine or phenytoin
Anaemia, thrombocytopenia or bone marrow failure
What do the side effects mean for the patient in a practical setting?
Patients on anti-epileptics and warfarin need close monitoring
Shouldn’t consume alcohol
Carbamazepine and phenytoin may decrease the effectiveness of oral contraceptive pills and some antibiotics
Valproate can increase the plasma concentration of other AED’s
Newer AEDs have less side effects or are metabolised in other ways
Which anti epileptic drug has the greatest risk of congenital malformation?
Valproate
Should not be prescribed to any women of childbearing age unless they meet the conditions of a pregnancy prevention programme
