Anti-epileptic Flashcards
Define the seizure?
Transient occurrence of symptoms due to abnormal electrical activity in the brain, leading to a disturbance of consciousness, behaviour, emotion, motor function or sensation
What receptor does glutamate act via?
NMDA receptor
What receptor does GABA act via?
GABAa receptor
Describe the effects of glutamate on NMDA receptors in terms of the effect on cations
Cation channels: let in Na and Ca and let K out
Depolarises the membrane
More likely to fire an action potential
Describe the effect of GABA on GABAa receptors and which channel is acted on
Cl- channel
Hyperpolarise membrane
Less likely to fire action potential
Describe a seizure in terms of the NTs
Loss of inhibitor signals (GABA)
Strong excitatory signals (Glutamate)
What are some causes of seizures?
Genetic differences in brain chemistry/receptor structure
Exogenous activation of receptors- drugs
Acquired changes in brain chemistry- drug withdrawal, metabolic changes
Damages to any of these networks e.g. strokes or tumours
What are the general symptoms and signs of epilepsy?
Not just shaking! Loss of consciousness Changes in muscle tone Aura Post octal period
What are the signs and symptoms for generalised seizures?
Loss of consciousness often with changes in muscle tone and tongue biting
What are the signs and symptoms for tonic clonic seizures?
Initial hypertonic phase, followed by rapid clonus (shaking/jerking)
What is epilepsy?
A tendency toward recurrent seizures unprovoked by a systemic or neurological insult
What is the actual definition of epilepsy?
Atleast two unprovoked seizures occurring more than 24 hrs apart
One unprovoked seizure and a probability of further seizures similar to the general recurrence risk after 2 unprovoked seizures
What are some potential stimuli for a reflex seizure?
Photogenic Musicogenic Thinking Eating Hot water immersion Reading Orgasn Movement
What are the 3 classifications of a seizure?
Focal
Generalised
Unknown
State some of the features/types of focal onset
Aware/impaired awareness
Motor/non-motor onset
Focal to bilateral tonic clonic
State some of the features/types of generalised onset
Motor- tonic/clonic
Non motor- absence
State some of the features/types of unknown onset
Motor- tonic/clonic
Non motor- absence
Unclassified
What is the difference between focal and generalised onset in terms of spread?
Focal- on 1 side of the brain, can spread but not rapidly
Generalised onset- bilateral involvement v rapidly
What is the difference between focal and generalised onset in awareness?
Generalised will always be unaware because too much of the brain is affected
Describe the distribution of generalised seizures
Originate at a point within and rapidly engage bilaterally distributed networks
Can include cortical and subcortical structures but not necessarily whole cortex
Describe the distribution of focal seizures
Originate within networks limited to one hemisphere and maybe discretely localised or more widely distributed
What is another term for generalised seizure?
Grand mal
What is another term for an absence seizure?
Petit mal
What is another term for a focal seizure?
Partial seizure
What is a provoked seizure and what can be inducers?
Seizure as a result of another medical condition, examples include: drug use or withdrawn Alcohol withdrawal head trauma and intracranial bleeding Metabolic disturbances CNS infections Febrile seizures in infants Uncontrolled hypertension
What is the key in treatment of unprovoked seizures?
It is key to treat both the siezure and the underlying condition. Unlikely to need prolonged AED treatment
What are some differentials for seizures?
SUncopal episodes e.g. vasovagal syncope Cardiac issues including reflex anorexic seizures, arrhythmias Movment disorders e.g. Parkinsons TIAs Migraines Non-epileptic attack disorders
What is always the initial management of a seizure?
A- Airway
B- Breathing, sats reading/O2
C- circulation, expect high HR, wary of BP
D- disability, will have reduced consciousness in general seizures
E- recovery position
What is status epileptics?
A seizure lasting more than 5 mins or more, or multiple seizures without a complete recovery between them
What is the pharmacological treatment regime for status?
Wait 5 minutes Benzodiazepine Benzodiazepine x2 Phenytoin (or Levetiracetam) Thiopentone/anaesthesia (call ITU)
What are benzodiazepines?
Class of GABA agonist that increase Cl- conductance so more negative resting potential, less likely to fire
No firing of neurones= no more seizure
What are some side effects of benzos?
Addiction, CVS collapse, airway issues
What can benzos also be used as?
Anxiolytics, sleep aids, alcohol withdrawal
What are the benzo options for status epilepticus?
IV Lorazepam
Rectal Diazepam
Buccal or intranasal Midazolam
What is the issue with using EEGs as an investigation for epilepsy?
Relies on capturing an episode or abnormal pattern but many people with epilepsy don’t have abnormal EEGs
What is the imaging method of choice for diagnosis?
MRI
May detect vascular or structural abnormalities
What are the 6 main AEDs?
Carbamazapine Phenytoin Na Valorate Lamotrigine Levetiracetam Benzodiazepine
What is a serious outcome of epilepsy?
Sudden unexplained death in epilepsy (SUDEP)
What is the main mechanism of action of Carbamazepine?
Sodium channel blocker
How does blocking of Na channels in central neurones help epilepsy?
It slows down the recovery of neurones from inactive to closed which reduces neuronal transmission
What are the 3 states of Na channels, and at which state do Na channel blockers work?
Open
Inactivated
Closed
Work at inactivated to increase refractory period
What are other uses of Carbamzepine?
Bipolar and chronic neuralgic pain
What are some side effects of Carbamazepine?
Suicidal toughts
Joint pain
Bone marrow failure
What is the mechanism of action of Phenytoin?
Na channel blocker
What are the uses of Phenytoin?
Status epileptics or as an adjunct in generalised seizures
Describe the metabolism of phenytoin
Zero order kinetics so it is eliminated at a constant rate so need to be careful about dosing
What are specific side effects for Phenytoin?
Bone marrow suppression
Hypotension
Arrythmias
What is the mechanism of action of Na Valporate?
Mix of GABA agonist effects and Na channel blocks as well as some Ca channel blocking
What does it say in the guidelines about Na Valporate?
1st line for generalised epilepsy
What are specific side effects of Na Valporate?
Liver failure
Pancreatitis
Lethargy
What is the MOA of Lamotrigine?
Na channel blocker and some Ca channel blocking
What is the main use of Lamotrigine?
Focal epilepsy
Used where Valporate is contraindicated
What is the MOA of Levetiracetam (Keppra)?
Synaptic vesicle glycoprotein binder, stops the release of NT into the cleft and reduced neuronal activity
What are the uses for Levetiracetam?
Focal and generalised seizures
What are the advantages of Levetiracetam?
Easy dosing
Well tolerated
Safe in pregnancy
What are the side effects of AEDs in general?
Tiredness/drowsiness Nausea/ vomiitng Mood changes and suicidal ideation Osteoporosis Rashes Anaemia, thrombocytopenia or bone marrow failure
What is the rash condition that could occur as a side effect and which drugs are most likely to cause it?
Steven Johnson Syndrome- mucocutaneous breakdown
Caused by Carbamazepine or Phenytoin
What are the implications of so many side effects of AEDs?
Anti-epileptics and warfarin need close monitoring
Ideally patients shouldn’t consume alcohol
Valporate can increase concentration of other AEDs
Carbamazepine and Phenytoin can impair antibiotic effectiveness and oral contraceptive effectiveness
What are some AEDs that induce CYP enzymes?
Phenytoin
Carbamazepine
Barbituates
What are some non AEDs that induce CYP enzymes?
Rifampicin
Alcohol
Sulphonylureas
What are some AEDs that inhibit CYP enzymes?
Valporate
Which AED is preferential in pregnant or potential conceiving mothers?
Lamotrigine and especially Levetiracetam
