Epilepsy + Anti Epileptic Drugs Flashcards
What is the key excitatory neurotransmitter?
What receptor in involved?
Glutamate
NMDA receptor
What is the key inhibitor neurotransmitter?
What receptor in involved?
GABA
Via GABAA/B receptors
What is a seizure?
Clinical manifestation of abnormal excessive excitation + synchronisation of a group of neurones within the brain
What determines how a seizure presents?
Where uncontrolled signalling occurs (can be anywhere in brain)
What is an epileptic seizure?
A transient occurrence of signs and/or symptoms due to abnormal excessive or synchoronous neuronal activity in the brain
What is epilepsy?
A disorder of the brain characterised by a predisposition to generate epileptic seizures unprovoked by a systemic or neurological insult
Risk factors of epilepsy
- premature birth
- complicated febrile seizure
- head trauma, infection or tumour
- cerebrovascular disease
- dementia + neurodegenerative disorders
Define prodrome
Early signs or symptoms a seizure may be coming hours to days before
What does the term ictal mean?
During a seizure
What does the term interictal mean?
Between seizures
What does the term post ictal mean?
After seizure subsides
What class of drug is carbamazepine?
Sodium channel blocker
What are uses of carbamazepine?
Epilepsy
Trigeminal neuralgia
What is the mechanism of action of carbamazepine?
Sodium channel blocker
- blocks VGNC in excitatory neurone
- reduces Ca2+ influx + glutamate release
what are adverse drug reactions of carbamazepine?
- dizziness
- skin ash
- eosinophilia
- leukopenia
- hyponatraemia
What are important drug drug interactions of carbamazepine?
- reduces COCP effect
- increases warfarin metabolism
- CYP3A4 inhibitors e.g.clarithryomycin + diltiazem increase [carbamazeipine]
Why should carbamazepine not been given during pregnancy?
Teratogenic
- Neural tube defects
- Bone marrow depression
- AV conduction issues
What is the mechanism of action of phenytoin?
Sodium channel blocker
- blocks VGNC in excitatory neurone
- reduces Ca2+ influx + glutamate
What are adverse drug reactions of phenytoin?
- dizziness
- skin rash
- visual disturbances
- arrhythmia
- gingival hyperplasia
What is gingival hyperplasia?
Overgrowth of gums
Classifications of sezuires
Focal onset
Generalised onset
Unknown onset
What is a tonic clonic seizure?
Typical epileptic fit
- tonic stage: loss of consciousness, stiff body
- clonic stage: limbs jerk, possible loss of bladder/bowel control
What is an absence seizure?
Loss of awareness of surroundings
- staring blankly into space
- looks like daydreaming
- slight jerking of body
- unable to remember them
What is a clonic seizure?
Body shakes + jerks but does not go stiff at start
What is a tonic seizure?
Body muscles become stiff
What is a atonic seizure?
All muscles suddenly relax
What class of drug is sodium valproate?
Anticonvulsant
Uses of sodium valproate
Most types of epilepsy
What is the mechanism of action for sodium valproate?
Increases GABA synthesis + transcription of channel coding genes
What are adverse drug reactions of sodium valproate?
- hepatotoxicity
- appetite stimulant
- alopecia
- thrombocytopenia
What are contraindications of sodium valproate?
teratogentic
- Avoided where pregnancy is possible
- Unless pregnancy prevention programme is in place
What are important drug drug interactions for sodium valproate?
Increases [lamotrigine] + [phenytoin] > decreases their action by displacing them off blood proteins
Outline the prescription of sodium valproate
No one under 55 will be newly prescribed unless two specialists agree there is no other effective or tolerated treatment, or there are reasons that the reproductive risk doesnt apply
Describe the pregnancy prevention programme
At least one highly effective contraceptive method
OR
Two complimentary forms including barrier
What class of drug is lamotrigine?
Na+ and Ca2+ channel blocker
What are the uses of lamotrigine?
Focal seizures
Generalised tonic clonic seizures
What is the mechanism of action of lamotrigine?
Na+ and Ca2+ channel blocker
- less enters excitatory neurone > less glutamate released to post synaptic neurone
What are adverse drug reactions of lamotrigine?
Aggression
Agitation
Hypersensitivity
What are important drug drug interactions of lamotrigine?
Sodium valproate + phenytoin increases [lamotrigene]
Oral contraceptive pill decreases [lamotrigene]
What are the uses of levetiracetam?
Focal seizures
What is the mechanism of action of levetiracetam?
Synaptic vesicle protein inhibition
- Reduces synchronised burst firing without affecting neuronal excitability
- reduced glutamate release from excitatory neurone
What are adverse drug reactions of levetiracetam?
Anxiety
Drowsiness
Dizziness
What are important drug drug interactions of levetiracetam?
CNS depressants
What is status epilepticus?
Condition where epileptic fits follow one another without recovery on consciousness between them
When is a seizure a medical emergency
- lasts >5 minutes
- status epilepticus (multiple seizure without recovery in between)
What is the stepwise approach of status epilepticus treatment
- benzodiazepines
- 2nd dose benzodiazepine
- 2nd line - levetiracetam or phenytoin or sodium valproate
- alternative 2nd line agent
- barbiturates + general anaesthesia
5-10 minute interval between each
What drug class should be administer first in the treatment of status epilepticus?
Benzodiazepines
Examples of benzodiazepiness
Diazepam
Lorazepam
Midazolam
Compare the duration action of midazolam + diazepam
midazolam: short actin
diazepam: longer acting
What benzodiazepine is better in hepatic dysfunction + why?
lorazepam
Phase 2 metabolism
What are the uses of benzodiazepines?
Anxiety
Status epilepticus
Insomnia associated with anxiety
What is the mechanism of action of benzodiazepines
- potentiate GABA activity at GABAA receptor
- hyperpolarisation of cell via increased Cl- influx
What are adverse drug reactions of benzodiazepines?
Ataxia
Depression
Drowsiness
Hypotension
Muscle weakness
Sleep disorders
What can high doses of benzodiazepines cause?
Respiratory depression
Why should benzodiazepines be used short term?
Addictive
Risk of overdose
What are important drug drug interactions of benzodiazepines?
Other CNS depressants
What is sudden unexplained death in epilepsy SUDEP?
Deaths in people with epilepsy who are otherwise healthy that are not caused by known causes
Relationship between carbamazepine + CYP450 enzymes
It induces CYP3A4 so increases its own metabolism
Describe a focal seizure
- remains conscious
- arises in one hemisphere of the brain
- split into aware + impaired awareness
- can have motor onset e.g. jolting
- or non motor onset e.g. smacking lips
Describe an simple focal seizure
- conscious
- normal awareness
- no post ictal symptoms
- arises in one hemisphere
What is a secondary generalised seizure?
Starts focal but then comes generalised
Describe a complex focal seizure
- conscious but impaired awareness
- can get post ictal symptoms e..g confusion, groggy
- often in temporal lobe
- arises in one hemisphere
Describe a generalised seizure
Arises in both hemispheres
Often unconscious
Types of generalised onset seizures
Tonic clonic
Tonic
Clonic
Atonic
Myoclonic (can be conscious)
Absence (can be conscious)
What is a myoclonic seizure?
Seizure of muscle or groups of muscles
Can be conscious
Examples of post ictal symptoms
Embarrassment
Confusion
Fatigue
Headache
Muscle aching/pain
Frustration
What is an aura?
A warning that a seizure in coming
Diagnosis of epilepsy
- electroencephalogram
- MRI
- detailed patient history + eyewitness accounts
What needs to be considered in women on COCP when prescribed carbamazepine?
Carbamazepine increases action of CYP450 enzymes on COCP so higher dose of COCP is needed
Uses of phenytoin
Second line status epilepticus
