Epilepsy and anti epileptic drugs Flashcards
What is a seizure?
- Clinical manifestation of abnormal excessive excitation and synchronisation of a group of neurones within the brain
- Sudden and temporary
What causes seizures?
- Loss of inhibitory signalling (GABA)
- Unchecked excitatory signalling
- Abnormally synchronised oscillations
- Post-tetanic potentiation
- Synaptic plasticity feedback mechanisms
Where do seizures occur?
- Anywhere in the brain
- Location of uncontrolled signalling dictates how a seizure presents
What can cause non-epileptic seizures?
- Drugs
- CNS infection
- Alcohol
- Hypoglycaemia
- Pyrexia
- Psychological
- Need to treat seizure AND underlying condition
What are psychological seizures?
- Dissociative seizures
- Caused by extreme emotional stress and many sufferers are epileptic
What are some conditions which may present with similar features to epilepsy?
- Vasovagal syncope
- Cardiac arrhythmias
- Panic attack
- TIA
- Migraine
What are some differentials for epilepsy in children?
- Febrile convulsions
- Breath-holding attacks
- Night terrors
- Stereotyped/ritualistic behaviour especially in those with a learning disability
What is epilepsy?
- A transient occurrence of signs and symptoms due to abnormal excessive or synchronous activity in the brain
- A disorder of the brain characterised by an enduring predisposition to generate epileptic seizures
What are the risk factors of epilepsy?
- Premature birth
- Complicated febrile seizure
- Genetic conditions e.g. tuberous sclerosis, neurofibromatosis
- Head trauma, infection, tumour
- Cerebrovascular disease
- Dementia and neurodegenerative disorders
How do we define epilepsy?
- Epilepsy is a tendency towards recurrent seizures unprovoked by a systemic or neurological insult
- At least two unprovoked (or reflex) seizures occurring more than 24 hours apart
- One unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk after two unprovoked seizures
What are the next steps that need to be made after a patient has a seizure?
- Urgent referral following first suspected seizure
- Assess risk of second seizure
- Provide information on recognising a further seizure
- First aid and safety guidance
How do we make an epilepsy diagnosis?
- Detailed patient history - eyewitness accounts/video
- Electroencephalogram (EEG) +/- video
- Neuroimaging - MRI first choice, CT, (PET/CT)
What are the symptoms of a focal aware seizure?
- Motor, somatosensory or psychic symptoms
- Consciousness is not impaired
What are the characteristics of a focal impaired awareness seizure?
- Temporal lobe
- Psychomotor
- Consciousness is impaired
What are the characteristics of clonic, tonic or tonic-clonic seizures?
- Initial rigid extensor spasm
- Respiration stops
- Defaecation
- Micturition and salivation occur
- This is the tonic phase
- Violent synchronous jerks
- This is the clonic phase
What is a myoclonic seizure?
- Seizures of a muscle or a group of muscles
What are the characteristics of an absence seizure?
- Abrupt loss of awareness of surroundings
- Little motor disturbance
What is an atonic seizure?
- Loss of muscle tone/strength
What is prodrome?
- Early signs or symptoms a seizure may be coming hours to days before
What is aura?
- A focal aware seizure leading to a secondary generalised seizure
What does ictal mean?
- During a seizure
- Interictal means between seizures
What is the post-ictal period?
- Begins as seizure subsides - lasts minutes to hours
- E.g. confusion, lack of consciousness, fatigue, headache, anxiety, frustration, embarrassment, muscle aching etc.
Give some examples of sodium channel blockers?
- Carbamazepine
- Phenytoin
- Sodium valproate
- Lamotrigine
How do sodium channel blocker work?
- Use-dependant blockade of Na+ channels
- Reduces Ca2+ influx
- Decreases glutamate
- Useful in most types of epilepsy
What are the adverse side effects of sodium channel blockers?
- Dizziness
- Skin rash
- Eosinophilia
- Leukopenia
- Hyponatraemia
What are the contraindications of sodium channel blockers?
- Teratogenic - cause neural tube defects, bone marrow depression, AV conduction issues
What are the DDIs of sodium channel blockers?
- Autoinduces its own metabolism to t1/2 reduces - increases dose
- It is a CYP3A4 inducer so decreases combined oral contraceptive pill effect and increases warfarin metabolism
- CYP3A4 inhibitors such as clarithromycin, diltiazem decrease carbamazepine concentration
Give some examples of other antiepileptics?
- Levetiracetam
What is the mechanism of action of phenytoin?
- Primarily use-dependant blockade of Na+ channels
- Used less often chronically now
- 2nd line in status epilepticus
What are the adverse side effects of phenytoin?
- Dizziness
- Skin rash
- Visual disturbances
- Gingival hyperplasia
- Arrhythmia
What are the contraindications of phenytoin?
- Teratogenic - facial and digital defects, acute porphyrias, bone marrow depression
What are the elimination kinetics of phenytoin?
- Zero order elimination kinetics
- Need to measure plasma concentration of drug (saliva sampling possible too
What are the DDIs of phenytoin?
- CYP inducer and decreases plasma concentration of many drugs
- E.g. COCP, Abx, other AEDs
