Treating seizures Flashcards by Maude Tanguay

What do we consider epilepsy and its tx?

at least 2 unprovoked epileptic seizures over 24h apart
antiepileptic drugs

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What is different about reactive seizures and their tx?

occurs as response to transient disturbance in function
reversible when cause is rectified
tx the underlying cause

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What are the mechanisms of action of antiepileptic drugs?

enhancement of inhibitory signalling via facilitation of GABA

reduction of excitatory signaling

modulation of membrane cation conductance

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How does gaba inhibit in the cns?

binds to 2 types of reveptors

GABAa-R: opens chloride ion channel causing influx into neuron hyperpolarising the neuronal membrane and reduces likelihood of action potential occuring

GABAb-R: increases potassium conductance which reduced neuronal hyperexcitability

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What drugs bind to GABAa-R?

barbiturates and benzodiazepines

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When should you start treating seizures?

cluster seizures
status epilepticus
severe post-ictal signs
worsening frequency or severity
2+ seizures in 6 months
underlying structural lesion

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What are the goals of treating seizures?

reduce frequency or eliminate seizures
reduce seizure severity
minimise seizure-related morbidity and mortality
avoid adverse effects

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What do we consider when choosing the drug to tx seizures?

efficacy: how well will it control the seizures
balanced with
tolerability: what adverse effects could it cause since its long term tx

balancing eliminating seizures with quality of life of ptx

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What are the 4 common drugs used to tx seizures?

phenobarbital (most evidence of effective)
imepitoin (most evidence of effective)
potassium bromide (somewhat effective)
levetiracetam

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Which of the seizure tx drugs are most safe/cause minimal side effects?

most safe: levetiracetam
then imepitoin
then phenobarbital
then potassium bromide

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What is an important characteristic of anticonvulsant medications?

need rapid and effective transport across the BBB

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What is first line tx for seizures in an otherwise healthy dog?

phenobarbital
or imepitoin (limited supplies, not licensed for clustur seizures)

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What is second line tx for seizures?

potassium bromide
when phenobarbital is at max therapeutic concentration but seizure control not sufficient or if phenobarbital is contraindicated

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What is phenobarbital?

GABA receptor agonist
very effective anticonvulsant

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What are the likely side effects of phenobarbital and when is it contraindicated?

contraindicated: hepatic dysfunction
poor liver function may = higher serum concentration
potent inducer of cytochrome p450 enzyme activity in liver
risk of withdrawal seizure if sudden stop tx

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How do we manage and monitor the use of phenobarbital in seizure ptx?

assess ham, biochem and BAST before tx

check serum levels 14 days after start, after dose changem if poor seizure control
check serum levels 3-6 months when stable

ensure safe and effective concentration in blood, guides decisions of dose changes

What are the acute adverse effects of phenobarbital?

sedation, ataxia, resolve in a week
neutropaenia, anaemia, thrombocytopaenia: STOP TX
acute hepatotoxicity, rapid elevation of ALT and bile acids: STOP TX
superficial necrolytic dermatitis
=/- pancreatitis, dyskinesia, anxiety

What are the chronic adverse effects of phenobarbital?

polyuria
polydipsia
polyphagia
elevation of ALKP and ALT
low T4 +/- high TSH
chronic hepatotoxicity

What is imepitoin?

low affinity partial agonist of benzodiazepine site of GABAa-R
licensed for idiopathic epilepsy

What makes imepitoin safer than phenobarbital?

reduced side effects
less sedation and ataxia
less polyuria, polydipsia, polyphagia
not contraindicated in hepatic compromise
1-2 days steady state

When is potassium bromide used as seizure tx?

as add-on tx once phenobarbital and/or imepitoin are at max dose but seizure control inadequate

Br ions cause neuronal membrane hyperpolarisation

What are the side effects of potassium bromide?

sedation, ataxia, weakness
polyuria, polydipsia, polyphagia
GI mucosal irritation: vomiting, diarrhoea (divide daily dose and admin with food)
necrotising pancreatitis: STOP TX

When does potassium bromide reach steady concentration?

120 days after start if tx/ dose change

What are the side effects of using potassium bromide?

excreted unchanged in urine
used with caution in animals with renal disease: reduced excretion

high diet chloride increase KBr excretion

What are reasons for seizure treatment failure?

poor compliance incorrect dose change in patient body weight incorrect dx patient develops tolerance to drug refractory seizures that don't respond to medications

What are add-on drugs for refractory seizures?

Usually: levetiracetam gabapentin, pregabalin, zonisamide, felbamate

What is the action of levetiracetam?

reduces excitatory neurotransmitter release, possibly neuroprotective rapid onset of action can be used as pulse therapy in dogs with cluster seizures

What should we inform/warn clients about seizure tx?

only 15-30% of idiopathtic epileptic dogs achieve seizure freedom with tx only 2/3 of dogs respond to AEDs majority of dogs = lifelong commitment = expensive AED use is associated with adverse side effects

When do we discontinue AEDs?

if life threatening adverse effects if seizure remission achieved (none for 1-2 years) slow decrease *could come back worse

What is the first line tx for seizures in cats?

phenobarbital 10-14 days steady state transdermal also possible

What are the main side effects of phenobarbital in cats?

sedation polyphagia ataxia elevated ALT and ALKP paraparesis

What are the main side effects of levetiracetam in cats?

hypersalivation sedation anorexia ataxia eliminated via kidneys: reduce dose if compromise

What are the effects of imepitoin and potassium bromide in cats?

imepitoin: not licensed, early studies shown safe potassium bromide: contraindicated, causes allergic pneumonitis

How can diet help manage IE?

could help improve seizure control and behavioural changes associated with epilepsy medium chain triglyceride supplemented diet! or MCT in oil based supplement

What is status epilepticus?

greater than 5 min of continuous epileptic seizures OR 2 or more seizures between which there is incomplete recovery of consciousness

Why is status epilepticus an emergency?

increased autonomic discharge = hypertension, tachycardia, cardiac arrhythmias gets worse with more CS if left untreated: multiple organ failure!

How do we approach status epilepticus in ER?

ABC IV access diazepam IV evaluated electrolytes/blood glucose + correct abnormalities longer acting AED: phenobarbital evaluate temp and start cooling if over 40 IVFT, oxygen, supportive care if continued seizure: CRI of midazolam, medetomidine or propofol

What are benzodiazepines?

first line drugs in emergency setting potent rapid onset 15-20n min effect diazepam, midazolam