Antiseizure Drugs Flashcards
What is the difference between epilepsy and seizures?
duration of symptoms
Epilepsy: chronic, recurrent
Seizure: finite, resolves
Seizure
transient disturbance of cerebral function due to an abnormal paroxysmal neuronal discharge in the brain
Seizure Classification: Focal Onset
aware or impaired awareness
motor or nonmotor onset
focal to bilateral tonic clonic
Seizure Classification: Generalized Onset
Motor
- tonic clonic
- other motor
Nonmotor (absence)
Seizure Classification: Unknown Onset
unwitnessed
Motor
- tonic clonic
- other motor
Nonmotor
Unclassified
What drugs lower the seizure threshold?
theophylline alcohol high dose phenothiazines antidepressants (especially buproprion) street drugs
Epilepsy: Risk Factors
premature birth w/ small gestational weight
perinatal injury (anoxia)
history of alcohol withdrawal seizures
history of febrile seizures
family history of seizures
Do we initiate therapy in a patient with:
no risk factors
normal MRI
normal EEG?
probability of seizure recurrence:
first year: <10%
end of second year: ~21%
weigh the risks and benefits
Do we initiate therapy in a patient if risk factors are present?
probability of seizure recurrence:
first year: 26%
end of second year: 41%
Do we initiate therapy in a patient with 2+ unprovoked seizures?
Yes
should be started on ASDs
Treatment Considerations
establish seizure type and epilepsy classification
age, gender, comorbidities, susceptibility to ADEs, other medications, adherence, insurance coverage, need for quick therapeutic levels
monotherapy is preferred
Factors favoring successful withdrawal of ASDs
seizure free for 2-4 years
complete seizure control w/in 1 year of onset
onset of seizures after 2 but before 35 years of age
AND
normal neurologic examination and EEG
you have to taper
Three Proposed Mechanisms of Antiseizure Drug Therapy
modification of ionic conductance (Na, Ca, K)
diminution of usually glutamatergic (excitatory) transmission
enhancement of GABAergic (inhibitory) transmission
Main Effect of Antiseizure Drug Therapy
inhibition of local generation of seizure discharges
- reduced ability of neurons to fire APs at high rate
- reduced neuronal synchronization
Generalized Absence: treatment
ethosuxumide
lamotrigine
valproic acid
alternatives for refractory:
clonazepam
topiramate
**gabapentin is ineffective
Ethosuximide: MOA, pharmokinetics
blocks voltage gated Ca channels
dec glutamate
long half life
Ethosuximide: clinical application
generalized absence
Ethosuximide: ADEs
gi distress ataxia drowsiness HEADACHE BLOOD DYSCRASIAS rash behavior changes
Lamotrigine: MOA, pharmokinetics
blocks voltage gated Na channels
dec glutamate
many drug interactions
Lamotrigine: clinical application
generalized tonic clonic
focal aware/impaired
focal/generalized myoclonic
generalized absence
Lamotrigine: ADEs
SERIOUS SKIN RASH (start low go slow) DIPLOPIA headache dizziness hemophagocytic lymphohistiocytosis
Valproate/Valproic Acid: MOA, pharmokinetics
inc/enhance GABA or mimic at post synaptic receptors
many drug interactions
Valproate/Valproic Acid: clinical application
generalized tonic clonic
focal aware/impaired
focal/generalized myoclonic
generalized absence
Valproate/Valproic Acid: ADEs
HEPATOTOXICITY TERATOGENIC PANCREATITIS nausea ALOPECIA weight gain vitamin D
Clonazepam: MOA, pharmokinetics
enhance GABA receptor response
> 80% bioavailability
Clonazepam: clinical application
generalized absence
focal/generalized myoclonic
infantile spasms
Clonazepam: ADEs
sedation
Topiramate: MOA, pharmokinetics
AMPA receptor inhibitor
blocks voltage gated Na
enhances GABA activity
hepatic and renal clearance
Topiramate: clinical application
generalized tonic clonic
generalized absence
focal aware/impaired
migraine
Topiramate: ADEs
COGNITIVE SLOWING CONFUSION sleepiness GI symptoms metabolic acidosis pregnancy category D
Medications to avoid with absence seizures
carbamazepine
vigabatrin
gabapentin
tiagabine
they aggravate absence seizures
Medications that are ineffective for absence seizures
phenytoin
phenobarbital
Tonic Clonic Seizures: treatment
topiramate lamotrigine levetiracetam perampanel phenytoin carbamazepine phenobarbital valproic acid
Levetiracetam: MOA, pharmokinetics
blocks synaptic release machinary SV2A
dec glutamate
minimal drug reactions
Levetiracetam: clinical application
generalized tonic clonic
focal aware/impaired
Levetiracetam: ADEs
BEHAVIORAL PROBLEMS HEADACHE sedation seizures - focal onset weakness
Focal Onset Seizures: treatment
Carbamazepine Lacosamide Phenobarbital Phenytoin Topiramate Valproic Acid
Alternatives: Oxcarbazepine Gabapentin Lamotrigine Levetiracetam Vigabatrinb Zonisamideb
Carbamazepine: MOA, pharmokinetics
blocks voltage gated Na channels
dec glutamate
many drug interactions
induces own metabolism
Carbamazepine: clinical application
generalized tonic clonic
focal aware/impaired
Carbamazepine: ADEs
SERIOUS DERMATOLOGIC REACTIONS AND HLA B1502 ALLELE IN ASIANS
APLASTIC ANEMIA
AGRANULOCYTOSIS
ATAXIA DIPLOPIA HYPONATREMIA METABOLIC BONE DISEASE nausea
Lacosamide: MOA, pharmokinetics
blocks voltage gated Na channels
dec glutamate
minimal drug interactions
Lacosamide: clinical application
generalized tonic clonic
focal aware/impaired
Lacosamide: ADEs
dizziness headache nausea inc lft's SMALL INC IN PR INTERVAL
Phenytoin: MOA, pharmokinetics
blocks voltage gated Na channels
dec glutamate
variable absorption
dose dependent elimination
protein binding
many drug interactions
BOX WARNING: cardiovascular risk associated w/ rapid infusion
Phenytoin: clinical application
generalized tonic clonic
focal aware/impaired
Phenytoin: ADEs
ATAXIA NYSTAGMUS GINGIVAL HYPERPLASIA HIRSUTISM NEUROPATHY FOLATE DEFICIENCY METABOLIC BONE DISEASE vitamind D
Phenobarbital: MOA, pharmokinetics
enhances GABA receptor responses
long half life
P450 inducer
many interactions
Phenobarbital: clinical applications
generalized tonic clonic
focal aware/impaired
Phenobarbital: ADEs
SEDATION INTELLECTUAL BLUNTING METABOLIC BONE DISEASE BEHAVIOR CHANGES ataxia vitamin D
Gabapentin: MOA, pharmokinetics
blocks synaptic release machinery Α2δ
dec glutamate
variable bioavailability
renal elimination
Gabapentin: clinical application
generalized tonic clonic
focal aware/impaired
Gabapentin: ADEs
ATAXIA
dizziness
SOMNOLENCE
WEIGHT GAIN
Pregabalin: MOA, pharmokinetics
blocks synaptic release machinery Α2δ
dec glutamate
renal elimination
Pregabalin: clinical application
focal aware/impaired
Pregabalin: ADEs
ATAXIA
dizziness
SOMNOLENCE
WEIGHT GAIN
Vigabatrin: MOA, pharmokinetics
GABA transaminase enhancing GABA activation
renal elimination
Vigabatrin: clinical application
focal aware/impaired
Vigabatrin: ADEs
PERMANENT VISION LOSS drowsiness dizziness psychosis ocular effects
Perampanel: MOA, pharmokinetics
blocks postsynaptic ionotropic glutamate receptors AMPA
dec glutamate
multiple metabolites with long half lives
substantial interactions
inc clearance by CYP3A
Perampanel: clinical application
focal aware/impaired
Perampanel: ADEs
SERIOUS PSYCHIATRIC AND BEHAVIORAL REACTIONS dizziness somnolence headache psychiatric syndromes
Tiagabine: MOA, pharmokinetics
GAT1 GABA transporter enhancing GABA activation
some drug interactions
Tiagabine: clinical application
focal aware/impaired
Tiagabine: ADEs
dizziness nervousness CONCENTRATION AND ATTENTION DIFFICULTY BEHAVIORAL DISTURBANES INC APPETITE
Myoclonic Seizures: treatment
levetiracetam
Alternatives: clonazepam topiramate valproic acid zonisamide
Zonisamide: MOA, pharmokinetics
blocks Na and Ca channels
**does NOT affect GABA activity
hepatic and renal clearance
Zonisamide: clinical application
generalized tonic clonic
focal aware/impaired
focal/generalized myoclonic
Zonisamide: ADEs
sedation COGNITIVE SLOWING PARESTHESIA RASH (sulfa based drug) KIDNEY STONES OLIGOHYDROSIS (low amniotic fluid)
Phenytoin: interactions
phenobarbital carbamazepine felbamate oxcarbazepine topiramate
fluoxetine fluconazole digoxin isoniazid oral contraceptives
Phenobarbital: interactions
valproate carbamazepine felbamate phenytoin lamotrigine
cyclosporine
nifedipine
theophylline
verapamil
Ethosuximide: interactions
valproate
phenobarbital
phenytoin
carbamazepine
rifampicin
Carbamazepine: interactions
phenytoin carbamazepine valproate phenobarbital primidone
fluoxetine
verapamil
macrolide antibiotics
isoniazid
Valproate: interactions
phenobarbital phenytoin carbamazepine lamotrigine felbamate ethosuximide primidone
Rifampin
Lamotrigine: interactions
valproate carbamazepine oxcarbazepine phenytoin phenobarbital primidone succinimides topiramate
sertraline
Rufinamide: interactions
Not metabolized via P450 enzymes, but antiseizure drug interactions may be present
Tiagabine: interactions
phenobarbital
phenytoin
carbamazepine
primidone
Topiramate: interactions
phenytoin
carbamazepine
lamotrigine
oral contraceptives
lithium?
Drugs with minimal or rare interactions
gabapentin
levetiracetam
pregabalin
vigabatrin
Cannabidiol
approved as adjunctive treatment for seizures related to Dravet and Lennox Gastaut syndromes
2+ years of age
assess ALT, AST, total bilirubin
interaction: CNS depressants
ADEs: hepatic dec appetite drowsiness anemia infections asthenia
Stiripentol
indicated for patients with Dravet syndrome who also take clobazam
Cannabidiol, Stiripentol
effective in dec drop seizures
