Pharmacotherapy of seizure disorders Flashcards
Lowering the seizure threshold: MEDICATIONS
Low doses:
Bupropion
Clozapine
Theophylline
Varenicline
Phenothiazine
CNS stimulants
High doses:
Imipenem
Lithium
Meperidine
Penicillin
Quinolones
Tramadol
Quality of life monitoring
seizure frequency
functional status
social functioning
mental health status-depression is a common comorbidity
cognition
number of doses of drug per day
cost of drug therapy
Risk factors of recurrence
< 2 years seizure free
onset of seizure after age 12
history of atypical febrile seizures
2-6 years before good seizures control in treatment
significant number of seizures
partial seizures
abnormal EEG throughout treatment
organic neurological disorder
withdrawal of phenytoin or valproate
Possible reasons for treatment failure
Failure to reach CNS target
Alteration of drug targets in CNS
Drugs missing the real target
Management: rule out pseudo-resistance
combo therapy
electrical/surgical intervention
Status Epilepticus
Defined as continuous seizure activity lasting 5 minutes or more, or two or more discrete seizures with incomplete recovery between seizures
Possible therapy: BENZOS, LORAZEPAM, MIDAZOLAM
Status Epilepticus Treatment
5-20 minutes
if seizure continues: IV lorazepam or IV midazolam
Phenytoin/Fosphenytoin Loading dose
Fosphenytoin–prodrug of phenytoin, better IV tolerance of dosing
20 mg PE (phenytoin equivalents)
Up to 150 mg PE/ minute IV infusion
CARDIAC MONITORING REQUIRED, MAY ALSO CAUSE “PURPLE GLOVE SYNDROME”
Oral Phenytoin dosing considerations
MUST obtain both phenytoin serum concentration and serum albumin in the same blood draw
Therapeutic serum concentration range: 10-20 mcg/ml
Valproate Loading dose
IV to PO conversion is 1:1 mg/mg
Desired serum concentration=80 mcg/ml (range 50-125 mcg/ml)
A12 inducer
Carbamazepine
Phenobarbital
Phenytoin
2C9 inducer
Carbamazepine
Phenobarbital
Phenytoin
3A4 inducer
Carbamazepine
Phenytoin
Lamotrigine
Oxcarbazepine
Phenobarbital
Topiramate
UGT inhibitor
Valproate
LAMOTRIGINE DOSING
UGT drug interactions
BOXED WARNING FOR SJS
WITH VALPROATE: 25 mg every other day x 14 days, 25 mg QD x 14 days, 50 mg QD x 7 days, 100 mg QD
WITHOUT UGT: 25 mg QD x14 days, 50 mg QD x 14 days, 100 mg QD x 7 days, 200 mg QD
WITH UGT inducers: DOUBLE DOSE OF REGULAR
Phenytoin
binds to the inactivated state of Na channels
phenytoin elimination kinetics are dose-dependent leading to non-linear PK
serum concentration: 10-20 mcg/ml
serum albumin
drug interactions: valproate, carbamazepine
SE: GI symptoms
arrhythmias
ataxia
nystagmus, blurred vision
gingival hyperplasia, hirsutism
hypersensitivity
osteoporosis (long term use)
Carbamazepine/Oxcarbazepine
binds and stabilizes the inactivated state of Na channels
drug interactions: phenytoin, valproate, clonazepam, ethosuximide
SE: GI symptoms
ataxia
blurred vision
sedation
hyponatremia/SIADH
SJS
Lacosamide
enhances inactivation of voltage-gated Na channels
SE: Increase PR interval, heart block, visual disturbances, skin reactions
Felbamate
3rd line
NMDA receptor antagonist
SE: hepatitis
Topiramate
AMPA and kainate receptor antagonist
SE: confusion, sedation
vision loss, mytopia, retinal detachment
weight loss
metabolic acidosis
nephrolithiasis
decrease sweating, heat intolerance
cognitive issues (word finding)–> slow dose titration
Vigabatrin
irreversible inhibitor of GABA transmission (GABA-T)
SE: Sedation, depression, visual field defects
Tiagabine
inhibits GABA transporter (GAT-1)
SE: sedation, ataxia
Gabapentin/Pregabalin
increase GABA release
decrease presynaptic Ca influx reducing glutamate
SE: sedation
ataxia
increase PR interval (pregabalin)
caution for respiratory depression
cns depressants, pulmonary, edler, renal impaired
Phenobarbital
drug of choice in infants up to 2 months of age
binds to allosteric site on GABAa receptor, increasing the DURATION of Cl- channel opening
SE: sedation, physical dependence
Drug interactions: CYP450 inducer
Diazepam/ clonazepam
D: status epilepticus tonic clonic
C: acute tx for epilepsy and ABSENCE seizures
binds to allosteric site of GABAa receptor increasing FREQUENCY of Cl- channel opening
SE: sedation, physical dependence
