Seizures 2 Flashcards
Epilepsy
Disease of brain - enduring predisposition to generate epileptic seizures. Having at least two unprovoked epileptic seizures >24 hr apart
Structural epilepsy vs idiopathic
**age of onset most reliable
Epileptic seizure type (gen or focal)
Normal inter-ictal exam
Single seizure vs cluster/status epilepticus
Concerns for structural epilepsy
Age of onset <6m or >6y
Interictal neurological abnormalities
Status
Drug resistance
Idiopathic epilepsy
Most common chronic neurological disease in dogs
GP manage approx 10 cases /year
Median age of death is 7 y
Median treatment duration is 2.3 years
Dogs w IE experience cognitive dysfunction at young age
Tier I confidence level IE
2 or more unprovoked epileptic seizures >24 apart
6m or 6y
Known breed for IE (boarder collie)
Normal CBC, Biochem, urinalysis
Normal inter-ictal exam (post ictal, anti seizure med)
Tier II confidence level IE
Meet tier I
Normal pre and post prandial bile acids
Normal MRI (post ictal changes)
Normal CSF analysis
Tier III confidence level IE
Meet tier I & II
EEG abnormalities
Genetics and epilepsy
~90% of purebred dogs
#2 concern of dog breeders (following cancer)
Prevalence in normal dog population ~0.75%
- incidence is unknown (new cases at sp time)
- prevalence in at risk breed >2% (overall cases)
Less common in cats
Incidence & heritability
Belgian tervuren - 17% prevalence, 0.77 heritability
Irish wolfhound - 18.3 prev, 0.87 heritability
Off spring of epileptic
Tervuren - 42% change offspring, 1% if normal parent
Lab retriever - 26% change of offspring
Bernese - 33% change of offspring
Choice of anti seizure drug therapy
No evidence based guidelines regarding choice of Anti seizure drugs in dogs
Long acting anti seizure drugs - first line
Phenobarbital
KBr
Imepitoin
Long acting anti seizure drug - cluster seizures
Levetiracetam
Long acting anti seizure drugs - adjunctive
Levetiracetam
Zonisamide
Gabepentin
Felbamate
Topiramate
Pregabalin
Fast acting ASD
Diazepam
Midazolam
Propofol
Phenobarbital
- is what type of drug
- mechanism
Barbiturate
Benzodiazepines
Mechanism of action is through GABAa channels
Bind to benzodiazepines receptors NOT barbiturate
^^ affinity for GABA to GABAa
High blood flow, low volume - lipophilic
Phenobarbital efficacy
Effictive in decreasing seizure frequency in approx 60-93% of dogs with IE when plasma concentrations are maintained in therapeutic range (25-35mcg.ml)
Therapeutic range for ASD
Min Effective dose - 15mcg/ml
Max tolerated dose = 40mcg/ml
LD - 150mg/kg
Loading dose - 15mg/kg iv
Oral dose - 2.5-3mg/kg
Pharmacokinetics
Oral bioavailability - 90%
Peak concentration- 4-8 hrs after admin
T1/2 avg 48 hr - takes 10 days to reach steady state
45% protein bound
75% met by liver
PB and metabolites are mainly renally excreted
CYP450 induction in 30-90 days
Pharmacokinetic drug interactions
Also metabolized by CYP450
Corticosteroids
Cyclosporine
Digoxin
Phenylbutazone
Levothyroxine
Zonisamide
Levetiracetam
Benzodiazepines
Side effects of ASDs
Sedation
Ataxia
Polyphagia
PU/PD
Symptoms are transient and can go away w time
Hepatotoxicity** - liver failure is possible
Idiosyncratic reactions
Hepatic failure
Hematologic abnormalities
Superficial necrolytic dermatitis
Hypoalubinemia
Superficial necrolytic dermatitis
Erosive dermatopathy w multifocal distribution
Footpads are effects w crusty hyperkeratosis
Mucocutanous junctions of mouth, eyes, genitalia, hocks, elbows, pinnae, interdigital areas
SND cause and prognsosi
Concurrent hepatic abnormalities and low plasma amino acid concentrations is linked to SND
Mean survival time is 12 weeks
Common w chronic use to PB
SND findings
Ultrasound findings: hypoechoic nodules w trabecular network surrounding nodules
Mild/moderate disorganization of lobular architecture from multifocal areas of neutrophilic inflammation & fibrosis
Monitoring
2 weeks
Check PB steady state, CBC, Biochem
3 months
PB levels (enzyme induction), CBC, Biochem
6 months
PB levels - monitoring, CBC, Biochem
12 months
PB levels - monitoring, CBC, Biochem
Monitoring math
Current drug dose/current drug level =
New drug dose/desired drug level
Monitoring math cross multiply
(current drug dose X desired level) / current drug level = new drug dose
primidone
Only FDA approved drug for ASD
Much more adverse effects than PB
KBr - potassium bromide
Acts on GABA receptors, keeping them open longer to allow more Cl- inside the cell
Acts similar to PB
Efficacy of KBr
65% of dogs respond well
PU/PD is less common but vomiting is much more common than PB
Idiosyncratic reactions
- personality changes, cough, ^ risk of pancreatitis & megaesophagus, skin problems
Pharmacokinetics of KBr
Oral bioavailability is 46%
T1/2 is 24-46 days - steady state 5 months
Not protein bound
KBr is excreted unchanged in urine
Undergoes tubular reabsorption in competition w chloride - high dietary chloride con increase the excretion of KBr & shortens half life
Pharmacokinetic interactions of KBr
Loop diuretics (furosemide) may enhance KBr elimination by blocking KBr reabsorption through renal tubular chloride channels
KBr should be avoided in dogs w renal dysfunction to prevent toxicity secondary to reduced renal elimination
Synergistic side effects possible w PB
Dosing and monitoring KBr
20-40mg/kg
20 if on PB, 40 if not on PB
625mg/kg loading dose given over 2-5 days
Check Br levels in 1m (w loading) or 3-5m (w/out loading)
Drug level = 1-3 mg/mL
ASD for IE
Start w PB or KBr
Use of Imepitoin
FDA approved for anxiety
Most used for IE
Improvements seen after 11w
76.5% of owners opted to continue Imepitoin
Pharmacokinetics of Imepitoin
T1/2 2-6 hours
Extensive liver metabolism
Excreted mainly via feces
Neither reduced kidney function or impaired liver function
Interactions at AE of Imepitoin
Benzodiazepines have 200x affinity for binding site
Levetiracetam
Binds to SV2A similarly to Keppra
Efficacy of Levetiracetam
Depends on cause of seizures
50-60% of patients w refractory epilepsy in reducing seizures
For structural epilepsy 52% have >50% reduction
64.8% reduction in cluster seizures
Pharmacokinetics of Levetiracetam
100% oral bioavalibity
Dosing Levetiracetam
Requires a loading dose of 60mg/kg
Maintenance dose = 20-30 mg/kg, extended release 30-40 mg/kg
Drug levels = 12-46 mcg/L
*good for patients w renal failure
Zonisamide
Binds to loading gate - making development of action potential harder
Pharmacokinetics of Zonisamide
T1/2 of 15 hrs
Almost complete oral absorption
Mainly undergoes hepatic metabolism via the CYP450 before being excreted by kidneys
Efficacy of Zonisamide
60% have >50% reduction in seizures as mono therapy or adjunctive therapy
Insufficient evidence for use in dogs
Side effects of Zonisamide
Ataxia, vomiting, sedation
Renal tubular acidosis - inhibition of carbonic anhydrase
Sulphonamide based anticonvulsant
Idiosyncratic reactions
Acute hepatic toxicity
Renal failure (in people)
Gabapentin
Alpha2 gamma 1 subunit
Calcium channel blocker
Pharmacokinetics
Dosing, safety, efficacy of gabapentin
Cat and anti seizure drugs
