Tx of seizures Flashcards
Single seizure causes (dont memorize)
-CNS depressant withdrawal (alc, benzo, antiseizure)
-acute illness (encephalitis, meningitis)
-toxicity (uremia, CO, lead)
-med (head trauma, hypoxia, fever)
-hypontremia, hypoglycemia, dehydration
-meds that lower seizure threshold
Chronic seizure causes (dont memorize)
-stroke/vasc probs
-intellectual disability
-neurodevelopmental or birth injury
-CNS neoplasms
-cerebral palsy
-head trauma
Genetic causes of seizures (dont memorize
-infantile seizures, childhood absence, and juvenile myoclonic epilepsy
-mutations in ion channel function
-mutations affecting CNS development/homeostasis
Medications for lowering seizure threshold
-bupropion
-clozapine
-theophylline
-varenicline
-phenothiazine antipsychotics
-CNS stimulants (amphetamines)
-high doses and renal function:
-carbapenems (imipenem)
-lithium
-meperidine
-penicillin
-quinolones
-tramadol
Pharmacotherapy goals in seizure
-optimal control w monotherapy
-partial seizures (focal) most common
-50% of pt will have good control w one drug
-most will have control w 2 drugs
-polytherapy necessary in drug-resistant epilepsy
Is seizure tx life long?
-no
-studies show successful withdrawal after 2-5 years seizure free
Risk factors for seizure occurence!!
-<2 years seizure free
-onset of seizure after age 12
-hx of atypical febrile seizures
-2-6 years of tx before good control
->30 seizures before control
-partial seizures (most common)
-abnormal EEG
-organic neurological disorder (traumatic brain injury, dementia)
-withdrawal of phenytoin or valproate
Drug-resistant epilepsy
-failure of at least 2 trials of antiseizure meds
-need to rule out pseudo-resistance (wrong drug or dx)
-try combo therapy or electrical/surgical intervention
possible reasons for tx failure in drug-resistant epilepsy
-failure to reach CNS target
-alteration of drug targets in CNS
-drug missing real target
Status Epilepticus
-continuous seizure activity lasting 5 min or more
-OR 2 or more discrete sz w incomplete recovery between sz
Status epilepticus tx options
-IV
-benzos (lorazepam or midazolam)!!
-others
Status epilepticus tx phases
-stabilization phase
-initial tx phase (IV lorazepam or midazolam)
-second tx phase (IV fosphenytoin, valproic acid, levetiracetam)
-third phase (repeat second phase)
Stabilization phase of status epilepticus tx (nah)
-0-5 min
-time sz
-start ECG and oxygen PRN
-check Rx serum concentration and electrolytes
-if BG low, treat w D25-D50 fluids
Initial treatment phase of status epilepticus tx
-5-20 min
-if sz continues: IV lorazepam or midazolam!!!
-alt: rectal diazepam or intranasal/buccal midazolam
Second treatment phase of status epilepticus tx
-20-40 min
-if sz continues:
-IV fosphenytoin
-IV valproic acid
-IV levetiracetam
-alt: phenobarbital if no access to above meds
Third phase of status epilepticus tx (nah)
-40-60 min
-repeat 2nd line therapy
-anesthetic doses of: thiopental, midazolam, phenobarbital, or propofol
-EEG monitoring
Phenytoin Loading dose
-contains propylene glycol = hyotension = limits infusion rate
-20mg/kg IV, may give again after 10min
-up to 50mg/min IV infusion
Fosphenytoin loading dose
-prodrug of phenytoin, better IV tolerance
-20mg phenytoin equivalents/kg, may give again in 10 min
-up to 150mg PE/min IV infusion
phenytoin/fosphenytoin monitoring
-cardiac monitoring required
-may also cause local reaction called purple glove syndrome (injection site purple)
Oral phenytoin dosing considerations
-need phenytoin serum concentration and serum albumin in same blood draw
adj concentration = [observed] / [(0.25 x albumin) +0.1]
-therapeutic range is 10-20mcg/mL
-phenytoin is highly protein bound, necessitating correction calculations based on serum albumin
-if adj concentration falls within therapeutic range, then there is unbound phenytoin within the therapeutic range of 1-2mcg/ml
Valproate loading dose conversion
-IV to PO conversion is 1:1 mg
-desired concentration 80mcg/mL (50-125)
1A2 inducers and 2C9 inducers
-carbamazepine
-phenobarbital
-phenytoin
-gonna wipe out each other and antipsychotics
3A4 inducers
-(ox)carbamazepine
-phenobarbital
-phenytoin
-lamotrigine
-topiramate
UGT inhibitor
-valproate
Lamotrigine dosing warning
-box warning for steven-johnson/toxic epidermal necrolysis
-UGT substrate, high initial serum concentrations associated w SJS/TEN
-watch dosing w UGT inducers or inhibitors
-half or double normal dose
-may see higher doses inpt if pt had prior tx w lamotrigine
-consider interactions
lamotrigine dosing w UGT inhibitor
-valproate
-25mg qod x 14 days
-25mg qd x 14 days
-50mg qd x 7 days
-100mg qd
lamotrigine dosing without UGT interactions
-25mg qd x 14d
-50mg qd x 14
-100mg qd x 7
-200mg qd
lamotrigine dosing w UGT inducers
-carbamazepine, phenytoin
-50mg qd x 14
-100mg qd x 14
-200mg qd x 7
-400mg qd
Anticonvulsant hypersensitivity syndrome
-associated w arene oxide intermediate (aromatic ring)
-genetic screen for HLA-B1502 before starting carbamazepine, oxcarbazepine, eslicarbazepine (AVOID if they have it)
-others, tricyclics
-HLA-A3101 in asians and northern europeans
-2C93 in asians
common causes of anticonvulsant hypersensitivity syndrome
-arene oxide intermediate (aromatic ring)
-HLA-B*1502 and carbamazepines (inc in asians)
-HLA-A3101 in northern european or asian
-asians also inc risk w use of pheytoin if 2C93
DRESS syndrome
-drug reaxtion w eosinophilia and systemic symptoms
-drug-induced hypersensitivity syndrome
-potentially life-threatening (mortality of 10%)
-2-6 weeks after initiation of drug therapy
-withdraw offending agent and add supportive care
DRESS syndrome risk factors
-carbamazepine
-cenobamate
-lamotrigine
-phenobarbital
-phenytoin
-valproate
-zonisamide
-HLA-A*3101 allele (asian and northern european)
Antisz drug withdrawal syndrome
-associated with abrupt dc of anticonvulsant
-recurrence of sz
-always taper meds instead of dc
antisz therapy in pregnancy
-Vd altered = change in concentrations
-sz may inc in pregnancy
-add supplemental folic acid (5mg qd)
-supplement vit K 10mg qd during last month of pregnancy
-give infant 1mg vit K IM at birth to dec risk of hemorrhagic disease
Drugs to avoid in pregnancy
-teratogenic:
-carbamazepine
-clonazepam
-fosphenytoin/pheytoin
-phenobarbital
-primidone
-topiramtate
-valproate not recommended (based on use bipolar vs sz vs migraine)
=neural tube defects and dec IQ in offspring
Contraceptive drug interactions
-mediated by P450 3A4 induction (estrogen is substrate)
-antisz meds that are 3A4 inducers lower efficacy
-use higher dose contraceptive (inc thromboemobolism risk)
-can use progestin-only (depot)
-IUD recommended
-estrogen can dec lamotrigine and lamotrigine dec estrogen
Cardiovascular adverse events
-arrhythmia: lamotrigine
-PR changes: lacosamide, pregabalin
-heart block: lacosamide
-arrhythmia: (FOS)phenytoin = AVOID in heart block
-valvular heart disease: fenfluramine
Effects on electrolytes, metabolic acidosis, mineral metabolism (bone loss)
-(ox)carbamazepine: hyponatremia, SIADH
-phenytoin: altered vit D metabolism, dec Ca = osteoporosis long-term
-topiramate: dec bicarb = metabolic acidosis, nephrolithiasis, dec sweating, heat intolerance, oligohydrosis
psychiatric side effects of antisz
-levetiracetam: psychosis, depression, suicide (children and adolescents)
-permapanel: box warning for neuropysch events (caution in psychosis)
-valproate: acute mental changes due to hyperammonemia, differentiate from sedation side effect
-Topiramate: cognitive dysfunction if dose inc too repidly
Visual abnormalities
-topiramate: vision loss, myopia, retinal detachment
-Vigabatrin Ci in pt w other risk factors for irreversible vision loss
Gabapentin and Pregabalin safety warning
-respiratory depression risk
-eval use and risk in pt taking other CNS depressants, has pulmonary disease, or elderly
Carbamazepine metabolism
-1A2, 2C9, 2C19, 3A4 and p-gcp inducer
-induces own metabolism
-oxcarbamazepine induces only 3A4
antisz w hyponatremia risk
-(ox)carbamazepine
Valproate monitoring
-can cause thrombocytopenia
-monitor CBC
-can cause PCOS, wt gain, sedation
Topiramate and zonisamide side effects
-wt loss
-oligohydrosis
-nephrolithiasis
Zonisamide CI in
-sulfa allergy
Phenytoin clinical pearls
-absorption dec w enteral feedings
-hold feedings 1-2 hours before and after admin
-can cause gingival hyperplasia and hirsutism
Gabapentin and pregabalin pearls
-renal elimination = dec dose w impairment
-peripheral edema and sedation
Lamotrigine warning
-arrhythmia risk in some pt
Lennox-Gastaut Syndrome
-multiple sz types from childhood
-intellectual disability
-sometimes unresponsive to tx
-WEED!
Dravet syndrome
-rare genetic epileptic encephalopathy w normal childhood development until sz in 1st year of life
=multiple sz type and developmental disability
-WEED!
Epidiolex
-cannabidiol oral solution
-indicated for Dravet and Lennox Gastaut syndrome
Ketogenic diet
-most often used in pediatric sz
-3:1 or 4:1 fats:carbs/proteins
-hyperlipidemia, wt loss, constipation, kidney stones, dec bone mass/growth
-adults respond only while on diet, effects in children may continue after diet is dc
Depression in epilepsy
-all antisz drugs carry warning for inc risk of suicidal thinking
-antidepressants do to in <24yo
-AVOID bupropion bc inc sz risk
Sz co-morbidities
-anxiety/depression
-dementia
-migraine
-heart disease
-peptic ulcer
-arthritis
