Seizures and Anticonvulsants Flashcards
where does an epileptic seizure localize?
prosencephalon
describe seizure/ictus/convulsion
clinical manifestation of excessive hypersynchronous neuronal activity in the cerebral cortex; a SUDDEN and TRANSIENT abnormal phenomenon of a motor, sensory, autonomic, or psychic nature resulting from transient dysfunction of the brain
nerve cells have to pass seizure threshold (so either change membrane potential or lower threshold so normal activity can = seizure)
compare and contrast reactive versus epileptic seizure
reactive: normal brain responding to metabolic or toxic issue
epileptic: true problem in the brain
-epilepsy: prone to chronic recurrent seizures
describe pathophysiology of seizures
imbalance of inhibitory impulses (GABA, hyperpolarize) and excitatory impulses (glutamate, depolarize)
describe the classifications of seizures based on etiology
- extracranial
- intracranial
- idiopathic: genetic cause
-“proven” in some breeds; autosomal recessive
-some breeds have a higher incidence
-not enough to use clinically yet
classify seizures based on type/presentation
- generalized: grand mal
- focal: neurons that are hypersynchronously depolarizing stay in one area instead of affecting the entire cerebrum
- focal: secondary generalization
describe common presentation of generalized seizures
- stiff and rigid posture: lateral recumbency
- excessive muscular activity (tonic/clonic)
-limbs paddling
-facial muscles (drawn expression)
-chewing/biting - excessive salivation
- urination and defecation
- unresponsive: myoclonic
cellularly: either entire cerebral cortex is firing, or somewhere in the thalamus there is a focal cortex that then diffusely projects to the cerebrum and then the whole cerebrum fires: AKA seizures localize to prosencephalic (thalamus versus cerebrum doesn’t really matter)
describe presentation of focal seizures
- isolated activity
- signs related to affected area of brain
-focal facial seizures
-behavioral (temporal) lobe): aggression, not directed at anything!! no trigger
-fly biting - may or may not be conscious
-simple: no alteration in consciousness
-complex: alteration in consciousness, psychomotor - may start focal and then generalize
what are 3 other episodic conditions that can mimic seizures and why?
- syncope: fainting, collapse bc decreased perfusion to brain
- narcolepsy/cataplexy: sudden change from awake to REM sleep without moving through sleep stages; all relaxed by eyes moving (no motor movements)
- vestibular disease: head rolling, eyes moving weird
- flea-zures: all itchy (inducible = not seizure!)
all can have muscular activity, autonomic signs, altered consciousness
must then further localize and obtain more history
describe a left prosencephalic lesion
- all deficits right side
- abnormal postural reactions
- responses imply cerebral input, decreased or absent menace, decreased or absent response to nasal stimuli
describe extracranial seizures; include diagnostic indications
- extracranial signs; systemic signs of illness
- abnormal neurological exam or interictal behavior
diagnostics:
-metabolic:
1. minimum database: CBC, chem, UA
2. specialized tests: bile acid stimulation, endocrine testing
-toxin:
1. history
2. supportive clinical signs:
-CBC, chem, UA
-specialized tests: lead levels and organophosphates
describe intracranial seizures and diagnostic indications
- abnormal neurological exam
- abnormal interictal behavior
- asymmetry!!!
diagnostics:
1. MRI
2. CSF analysis: inflammation or infection
3. serology/CSF measurement: check for
-toxoplasmosis
-neosporosis
-canine distemper
-cryptococcosis
-other infections
describe diagnostic characteristics of idiopathic epilepsy
- breed: NOT/unlikely brachycephalic and toy breeds
-very few boxers within age range have idiopathic epilepsy (more likely to have the cancer than epilepsy) - age: 1-5 years old
-if older or right at 5 remember neoplasia also causes seizures! - normal neuro exam
- normal interictal behavior
- onset of seizures; chronic disease with a slower/chronic onset (once a month seizure, not multiple seizures in a day)
if you suspect idiopathic epilepsy, do you initiate treatment at the FIRST seizure?
no. wait for another one before giving drugs!!; is okay to wait, watch, and monitor
treatment is based on seizure frequency:
1. individualized
2. very unpredictable
-some have stable frequency, others go a long time without seizures
3. consensus statement:
-begin treatment when acute, repetitive (status epilepticus or cluster)
-prolonged, severe, or unusual postictal period
describe post-ictal
- period of time following a seizure
- may last from minutes to hours (less than 24 hours)
- abnormal behavior: range from somnolent to hyperactive
- blind: bilaterally affected, normal pupils
- urinate or defecate
- hungry/thirsty
- can look like nearly anything!!
when to start anticonvulsant medication?
- interictal period <6 weeks: treat!
- 6-8 weeks: grey zone: base decision on client and severity
- > 8 weeks: monitor frequency
- if present with cluster seizures of status epilepticus, definitely treat!!
anticonvulsants have side effects, so trying to balance when to start meds and balance client expectations
what is the first line anticonvulsant drug? what are 3 second line drugs?
phenobarbital: most effective as a sole therapy
-most widely used
-administered PO, IM, IV
-effective in 80% of idiopathic epileptic dogs
-steady state: reached in approx 2-3 weeks
-owners like
- potassium bromide:
- levetiracetam
- zonidamide
describe phenobarbital
- barbiturate (controlled)
- high oral bioavailability, rapidly absorbed (2hrs), peak concentration in 4-8 hrs; half life 48 hrs
-can give PO, IM, IV - metabolized in liver; increases P450 system in liver
- steady state reached in 2-3 weeks!!
- therapeutic serum concentration:
-dogs: 15-35mg/dl
-cats: 20-30mg/dl
dosing:
start at 2/2mg/kg orally BID
loading dose: 16-20mg/kg
describe side effects of phenobarbital
most common/seen in ALL:
1. sedation (temporary) to move away from seizure threshold; should be acclimated/normal within a month
- increased thirst, appetite, urination, defecation
-P/U, P/D, P/P - hepatotoxicity:
-long term/high doses related
-can monitor liver values, keep dose as low as possible to try to ensure not hurting liver!
-in all dogs, will see SAP increase (fine) but ALT can also increase (not so fine, monitor closely!!)
-if see GUAC on chemistry, maybe come off drug, bc means lost a lot of liver
less common: but serious
1. cytopenia on CBC: indicates bone marrow toxicity
-neutropenia, thrombocytopenia, anemia
-idiosyncratic (not dose related), but DOES occur within 1st 3 months of treatment
-if see, consider stopping because not dose related so cannot control for
- dermatological adverse reaction (VERY RARE): superficial necrolytic dermatitis/hepatocutaneous syndrome
describe effects of phenobarbital on thyroid function
doesn’t make the animal hypothyroid, but makes the thyroid values look decreased!
tricky bc signs of hypothyroid and effects of phenobarbital overlap significantly
describe monitoring and balance and clinical effect of phenobarbital
- want a dose that is effective with the least side effects
- therapeutic range is 15-35mg/dl, but as dosage increases, so do side effects
- clinical effect:
-serum levels reach steady state at 2-3 weeks
-evaluate hepatic metabolism closely in the first 2-3 weeks and then yearly min database! - if below therapeutic range with frequent seizures, increase dosage to therapeutic range
- if within therapeutic range with frequent seizures AND unacceptable side effects, add in adjunctive therapy
- if below therapeutic range and no seizures, keep monitoring
what is the most common adjunctive/additional anticonvulsant drug? describe
- potassium bromide; can reduce seizures and allow for a reduction in phenobarbital dosage
- long half life!
-steady state reached in approximately 3 months
-no hepatic metabolism: renal elimination based on GRF
-competes with Cl- and hyperpolarizes cell, moving away from seizure threshold as the cell is less likely to depolarize - synergistic effects
-if add KBr, leave phenobarb dose, monitor effect
-if positive effect, gradually reduce phenobarb dose - dosing and therapeutic range:
-dogs starting maintenance dose: 30-40mg/kg orally SID
-therapeutic range when combine with phenobarb: 0.8-2.5 mg/ml
-as monotherapy: up to 3mg/ml
describe side effects of potassium bromide
- toxicity:
-renal disease
-a diet with lower sodium with increase the bromide concentration and can injure the kidney!
-if geriatric or a dog with kidney disease and want a low sodium kidney diet, just remember will increase bromide if taking this med - other side effects same as phenobarb
-sedation (longer onset)
-unsteady gait (tetra and paraparesis, somewhat transient)
-obtunded/stupor/coma
-cranial nerve (PLR, mydriasis)
-P/U, P/D, P/P - megaesophagus (RARE)
-take off drug and goes away within a week - pancreatitis: (RARE)
-if history of pancreatitis, don’t put that patient on this drug
how to treat potassium bromide toxicity?
- mild: reduce dosage
- moderate:
-skip dosing until improved
-start back at lower dosage
-long half life so won’t go away super quick - severe:
-diuresis with saline (0.9% NaCl)
describe 3rd line drugs for if patient not responding to phenobarb + potassium bromide
- levetiracetam (Keppra)
-100% bioavailability IM or PO; excreted through kidneys
-short half life (3-4 hours alone or 1.5-2hrs with phenobarb) and short peak (steady state reached in 24 hours)
-side effects: mild sedation, GI intolerance (V/D), ataxia, behavioral changes
-as monotherapy: not super effective anticonvulsant
-if use with phenobarb, will decrease peak and increase clearance of Keppra so now have to dose Keppra more frequently
-good for dogs that have pre-existing disease where you don’t want to add excessive sedation to seizure control! (intracranial neoplasm, dull mental state, older dogs)
- zonisamide (zonegram): also not a very effective anticonvulsant
-half-life 13-18 hours, steady state reached in 4 days
-side effects: sedation (mild), GI intolerance, ataxia, acute idiosyncratic hepatic necrosis, renal tubular acidosis, blood dyscrasia, aggression, dermatologic erythema multiforme
-just monitor like phenobarb
- prebagalin (lyrica)
- gabapentin
