Treating Seizures Flashcards
What are the three mechanism of actions of anti epileptic drugs?
i. Enhancement of inhibitory signalling via facilitation of GABA
ii. Reduction of excitatory signalling
iii. Modulation of membrane cation conductance
What is GABA? How does this relate to seizure treatment?
γ -Aminobutyric acid- its the the main inhibitory neurotransmitter in the CNS
How do GABAA receptors work to reduce seizures?
Medication binds to the receptor in the neuron- causing chloride influx into the neuron, this hyperpolarises the neuronal membrane & reduces the likelihood of an action potential occurring
What is the result of medication binding to a GABAB receptor?
Increases potassium conductance
What are the indications for the prescription of Anti Epileptic drugs? (5)
Cluster seizures (2 or more seizures within 24 hours)
Status epilepticus
Severe post-ictal signs
Worsening frequency or severity of seizures
2+ seizures within 6 months
What does Anti Epileptic treatment aim to do? (3)
- Reduce or eliminate seizures
- Reduce seizure severity
- Minimise seizure-related morbidity & mortality
In order of highest tolerability and stability, give the four main AED’s?
Levetiracetam > Imepitoin > Phenobarbital > Potassium Bromide
When is Phenobarbital contraindicated?
- Not licensed for clustered seizures
- In hepatic disease (its hepatically metabolised)
What is the mechanism of action of Phenobarbital?
Acts as a GABA receptor agonist
What is the time taken for Phenobarbital to reach a steady state/ concentration in the body?
10-14 days.. so check serum levels 14 days after starting treatment or after a dose change
What are some acute adverse effects of Phenobarbital? (4)
Sedation & Ataxia (resolves in 7 days)
Neutropenia & Anaemia
Acute hepatoxicity
Superficial necrolytic dermatitis
What are some chronic adverse effects of Phenobarbital?
Polyuria/ Polydipsia
Low T4 & high TSH
Chronic Hepatoxicity
What type of epilepsy is Imepitoin used for?
Idiopathic epilepsy
What are the benefits to using Imepitoin when compared to Phenobarbital?
Reduced side effects compared to phenobarbital
Not contraindicated in hepatic compromised patients
In what way do we use potassium bromide as an AED?
used as an add on therapy- once phenobarbital and/or imepitoin are at maximum dose but seizure control remains inadequate
What are some possible side effects of Potassium Bromide? (4)
Sedation
Polyuria, polydipsia
Can cause GI mucosal irritation e.g. Vomiting, diarrhoea- this can be mitigated by dividing the daily dose and administering it with food
Can also cause necrotising pancreatitis
What time does it take for Potassium Bromide to reach a steady state in the body?
120 days- so assess serum concentration 120 days after initiation of treatment
Give an example of an add on drug used for refractory seizures?
Levetiracetam
How does Levetiracetam work?
Reduces excitatory neurotransmitter release so possibly neuroprotective
How would we use Levetiracetam to treat cluster seizures?
Pulse therapy- start administration after a seizure, and continue until 72 hours of seizure freedom has been achieved, then stop
When would we discontinue or reduce the use of AEDs?
If patient has had nso seizures for 1-2 years- decrease dose by ~20 % every 4 weeks to minimize risk of withdrawal seizures and status epilepticus
What is recommended as the first line treatment for seizures in cats and how is administered and why?
Phenobarbital-
Transdermal is a preferable route of administration even though oral is possible- think orally medicating a cat everyday- no thanks!
How does dietary management aid in the treatment of Seizures?
Potentially improves behavioural changes associated with epilepsy such as anxiety- supplement with a medium chain triglyceride e.g. Purina Neurocare
What is Status Epilepticus?
greater than 5 minutes of continuous epileptic seizures or two or more seizures between which there is incomplete recovery of consciousness
Why is Status Epilepticus such an emergency?
Increased autonomic discharge leads to hypertension, tachycardia, cardiac arrhythmias
Then to hyperthermia, lactic acidosis, hyperkalemia which ultimately progresses to hypotension, hypoxemia, hypoglycaemia as energy demand exceeds supply
… Leading to ORGAN FAILURE
How do we approach treating Status Epilepticus?
Administer Diazepam & correct electrolyte abnormalities > Administer long acting AED such as Phenobarbital and start cooling the body temperature > If continued seizure activity then consider Propofol or Medetomidine
What is the first line drug to treat Status Epilepticus and why?
Benzodiazepine-
Potent, rapid onset with 15-20 minutes duration of effect
Can be administered rectally if no IV access or via intranasal administration
