Anticonvulsants Flashcards
seizure
clinical manifestation of excessive hypersynchronous neuronal activity
Two major excitatory NTs
aspartate and glutamate
Two major inhibitory NTs
GABA and glycine
epilepsy
enduring disorder characterized by recurrent seizures - a SYMPTOM
cluster
2+ seizures in 24 hours
status epilepticus
5+ minute seizure OR 2 or more seizures without return to consciousness
refractory epilepsy
pharamcoresistant
generalized
bilateral involvement, loss of consciousness
tonic
increased muscle tone
clonic
shaking/paddling
focal
unilateral/regional signs, electric impulses from opposite hemisphere
3 Components of a Seizure
- Preictal
- Ictal
- Postictal
Etiology Based Seizure Classification
- Idiopathic
- Structural
What % of epilepsy patients are pharmacoresistant?
~25%
4 Reasons Seizure Treatment May Be Required
- Identifiable Structural Lesion or prior hx of brain dz/injury
- Acute repetitive seizures or status epilepticus
- Two or more isolated events within a six month period
- Prolonged, severe, or unusual post-ictal events
Objective of Anticonvulsant Therapy?
decrease the frequency, duration, and intensity of seizure (by about 50% or more)
Are anti-convulsants lipid soluble?
yes, they need to cross the BBB
Anticonvulsant MOAs
increase inhibition [of GABA or glycine] or decrease excitation [of aspartate and glutamate]
Benzos are what schedule drug?
Schedule IV (controlled)
Benzo MOA
targets postsynaptic GABA receptors to increase about of GABA in the synapse
Benzo Examples
diazepam, clorazepam, midazolam, clorazepate, lorazepam
Benzo Metabolism
liver
Most common anticonvulsant in vet med?
phenobarbital
At what level does phenobarb cause hepatotoxicity?
greater than 35 ug/mL
3 Bloodwork Changes in Phenobarb Patients
- Increased ALP
- Low T4/High TSH
- Hypertriglyceridemia
Autoinduction
induces hepatic microsomal enzymes (P450) which reduces the half-life over time –> increased dosing or frequency may be required
Can you use potassium bromide in cats?
NO
Can you use phenobarb in cats?
yes
(also autoinduction not a problem in cats)
Bromide MOA
unclear but competes with chloride in the synapse to keep the membrane hyperpolarized
Metabolism of Potassium Bromide occurs in what organ?
kidney!
Do bromide and phenobarb have a wide or narrow therapeutic index?
narrow (monitor)
psuedohyperchloremia
fake increase in serum chloride from benchtop analyzers because it can misidentify bromide as chloride
Effect of Sodium on Bromide Therapy
high sodium diet means the patient will pee out all the bromide
Side Effect of Bromide in Cats?
pneumonitis (irreversible)
Bromidism
side effect of bromide therapy resulting in sedation, ataxia, tremors, and possibly pelvic limb paralysis
Which anticonvulsant is a gastric irritant?
bromide
Keppra MOA
bind to presynaptic vesicle SV2A to prevent glutamate release
Keppra Metabolism
kidney
Keppra Bioavailability?
100%
Bloodwork Changes due to Keppra
NONE
Side Effects of Keppra?
possible behavior change, transient sedation (~1 week), ataxia (in polytherapy)
Keppra + Phenobarb
phenobarb will decrease the half-life of Keppra so those patients need a higher dose
Which anticonvulsant may have an anti-kindling effect?
Keppra (neuroprotective properties that may decrease brain damage)
Zonisamide MOA
post-synaptically increases GABA and presynaptically decreases glutamate
Does zonisamide have a wide or narrow therapeutic index?
wide
Bloodwork Changes for Zonisamide
none usually
can have metabolic acidosis (since it binds to carbonic anhydrase in the RBCs)
Pregabalin and Gabapentin MOA
presynaptic inhibits glutamate release by decreasing Calcium influx