Letcure 24 - Epilepsy And Antiepileptics Flashcards
What is the main excitatory neurotransmitter?
Glutamate
What is the main receptor which the excitatory neurotransmitter glutamate acts at?
NMDA receptor
What is the main inhibitory neurotransmitter in the brain?
GABA
What are the receptors which the main inhibitory neurotransmitter GABA acts on in the brain?
GABA alpha and beta receptors
What happens when glutamate binds to NMDA receptors?
Influx of Na+ and Ca2+ leading to depolarisation
What happens when GABA binds to a GABA receptor?
Cl- influx
Causes membrane hyperpolarisation reducing firing
What are seizures?
Clinical manifestation of abnormal excessive excitation and synchronisation of a group of neurones within the brain (is sudden and temporary)
What causes seizures?
Loss of inhibitory signalling
Unchecked excitatory signalling
Post tetanic potentiation
What are non epileptic seizures called?
Dissociative seizures
What are some causes of dissociative (non epileptic seizures)?
Drugs
CNS infection
Alcohol
Hypoglycaemia
Pyrexia
What are some causes of non epileptic seizures in kids?
Febrile convulsions
Breath-holding attacks
Night terrors
Stereotyped ritualistic behaviour
What is an epileptic seizure?
A transient occurrence of signs and or symptoms due to abnormal excessive or synchronous neuronal activity in the brain
What is epilepsy?
A disorder of the brain characterised by an enduring predisposition to generate epileptic seizures and by the neurobiological, cognitive, psychological and social consequences of this condition
What are the risk factors for epilepsy?
Premature
Complicated febrile seizure (can be linked to whooping cough)
Genetic conditions (tuberous Sclerosis, neuorfibromatosis)
Head trauma, infection, tumour
Cererbrovascular disease
Dementia and Neurodegenerative disorders
What is epilepsy simplified?
Tendency toward recurrent seizures unprovoked by a systemic or neurological insult
What is an epilepsy syndrome?
A condition that is not epilepsy but causes epilepsy like condition
What is an epilepsy syndrome?
GLUT 1 deficiency
How do we diagnose epilepsy?
Urgent referral following first suspected seizure
Assess risk of second seizure
First aid and saftey. Guidance
Detailed Hx
EEG
Neuroimgaing
What neuroimaging is first line for diagnosing epilepsy?
MRI
What are the 2 types of seizures that can be seen in epilepsy?
Focal seizures
Generalised seizures
What are focal seizures?
Seizures that often have focal impaired awareness
So remain conscious but unaware of what’s happening
What is a tonic-clonic seizure?
Where there’s violent jerking
Why do you have to give IV fluids when having tonic-clinic seizures?
Hyperhidrosis occurs (excess sweating)
What are the 2 main types of seizure?
Focal onset
Generalised onset
What are the types of focal onset seizures?
Aware, impaired awareness
Can be motor onset and nonmotor onset
What are the types of generalised onset seizures?
Motor seizures (tonic-cloning)
Non motor (absence)
What are the 3 main types of seizures?
Generalised seizures
Absence seizures
Focal seizure
What is prodrome?
Early signs or symptoms a seizure may be coming hours to days before
What is aura?
A warning,focal awareness seizure leading to secondary generalised
What is the meaning of ictal?
During a seizure
What is interictal?
Between seizures in reference t EEG
What is post ictal?
Begins as seizure subsides last minutes to hours
Confusion, lack of consciousness, fatigue, headache, anxiety, frustration, embarrassment, muscle aching or pain
What is sudden unexplained death in epilepsy?
Sudden Death that occurs in patients with epilepsy that not linked to seizures
What is the mechanism of action of carbamazepine?
Blockage of Na+ channels leading to reduced Ca2+ influx leading to reduced glutamate release (excitatory)
What is carbamazepine used to treat?
Epilepsy
Trigeminal neuralgia
What are the adverse drug reactions of Carbamazepine?
Dizziness
Skin rash (Steven Johnson syndrome)
Eosinophilia
Leukopenia
Hyponatraemia
What are the contraindications to carbamazepine?
Teratogenic (neural tube defects)
Bone marrow depression
AV conduction issues
HLA-B 1502 allele
What are the drug-drug interactions of carbamazepine?
Is a CYP3A4 inducer (dec effect of COCP) and inc Warfarin metabolism (reduced effect of warfarin)
CYP3A4 inhibitors affect it: clarithryomycin, diltiazem increasing the concentration of carbamazepine
It induces its own metabolism reducing its half life needed a dose increased
What is the mechanism of action of phenytoin?
Blocks Na+ channels, preventing Ca2+ influx and reducing glutamate release
exactly the Same as carbamazepine
What is phenytoin used for?
2nd line in status epilepticus
Why is dosing with phenytoin very important?
Has zero order elimination kinetics so rate of elimination is constant
Therapeutic window is narrow and small change in dose can drastically change plasma conc
What are the adverse reactions of phenytoin?
Lots
Dizziness
Skin rash (Steven Johnson syndrome)
Visual disturbance
Gingival hyperplasia
Arrhythmia
What are the contraindications to phenytoin?
Is teratogenic often cuasing facial and digital defects
Acute porphyria’s
Bone marrow depression
What are the drug drug interactions phenytoin?
Is a CYP inducer so decreases the plasma conc of drugs like COCP, Abx and other antiepileptics
What is the mechanism of action of sodium valproate?
Multiple sites including Na+ channels
Increases GABA synthesis and transcription of channel coding genes
What is sodium valproate used for?
Epilepsy
What are the adverse effects of sodium valproate?
Hepatotoxicity
Appetite stimulant
Alopecia
Thrombocytopenia
What are the contraindications of sodium valproate?
Teratogenic (causes major malformation in pregancy)
Avoided in pregnancy unless pregnancy programme in place
What are the drug drug interactions of sodium valproate?
It increases the conc of Lamotrigine, phenytoin and sodium valproate
Hepatotoxicity
Why do you need a family planing pregancy prevention programme for women’s taking Anti epileptics?
Teratogenic
What anti epileptic drug should only ever be given in women of child bearing age if a pregnancy prevention programme is in place/
Sodium valproate
What is the pregancy prevention programme?
At least one highly effective contraception method or two complimentary forms including barrier method
What is the method of action of lamotrigine?
Na+and Ca2+ channel blocker selectively blocking neurones
Selective for dendrites of pyramidal neurones
What are the adverse effects of lamotrigine?
Aggression
Agitation
Hypersensitivity
What are the contraindications of lamotrigine?
Phase 2 metabolism makes it have a long half life
What are the drug-drug interactions of lamotrigine?
Sodium valproate increases conc of lamotrigine
Phenytoin and oral contraceptives decreases conc of lamotrigine
What is the mechanism of action of levetiracetam?
Inhibts synaptic vesicle protein 2A so decreases synchronised burst firing without affecting neuronal excitability
What is levetiracetam used for?
Focal seizures including secondary generalisation
Safer options for PREGNANCY
What are the adverse effects of levetiracetam?
Anxiety
Drowsiness
Dizziness
All common to all anti epileptics
What are the contraindications to levetiracetam?
QT prolonging risk factors
What are the drug drug interactions of levetiracetam?
CNS depressants which is the same with other anti epileptics
How do you decide to initiate and titrate doses of antiepileptics?
Start at low dose and mono therapy is desirable
Aim to be seizure free balanced with acceptable side efffect profile
What are the benzodiazepine drugs?
Diazepam
Lorazepam
Midazolam
What is the mechanism of action of the benzodiazepines?
(Diazepam, lorazepam and midazolam)
Bind to Allosteric site at GABA receptors enchancing hte activity of GABA to hyperpolarising membranes via Cl- influx
How does the duration of action of midazolam differ to diazepam?
Midazolam = short acting
Diazepam = longer acting
Which benzodiazepine is best in hepatic dysfunction?
Lorazepam
What are the adverse effects of benzodiazepines?
Ataxia
Depression
Drowsiness
Hypotension
Muscle weakness
Sleep disorders
What are the contraindications of benzodiazepines?
Cause resp depression at high doses
What are the drug-drug interactions of benzodiazepines?
Other CNS depressants
What is the first line drug in convulsive status epilepticus?
IV lorazepam
Buccal midazolam if cant get a line in
Or per rectal diazepam
What is convulsive status epilepticus?
Epileptic seizure lasting 5 minutes or more or multiple seizures without recovery in between
A MEDICAL EMERGENCY
What is the steps of treatment for status epilepticus?
Benzodiazepine first line (IV LORAZEPAM)
Immediately prepare 2nd dose of benzodiazepine
Give 2nd dose after 5-10mins
If that doesn’t work give 2nd line levetiracetam, phenytoin or sodium valproate
If doesn’t work give a different second line agent to what you gave
If doesn’t work then give barbiturates or general anaesthesia
Always get help. And treat metabolic derangement like glucose and electrolytes
What is important when prescribing antiepileptics?
Always stick to the same specific brand or generics cuz they may differ slightly
Specific brand and generic may be same but there may be differences between generics
