Seizures Flashcards
Causes of seizures
Congenital defects (cerebral palsy) Hypoxia Trauma (incl. brain surgery) Cancer (tumors) Alcohol or drugs (incl. withdrawal) Elevated body temp (febrile) Electrolyte disturbances Drugs: Meperidine
Partial seizures
Simple
Complex
Secondarily generalized
Generalized seizures
Absence Tonic Clonic Tonic-clonic (grand mal) Myoclonic Atonic
Seizure type guidelines
Identification is very important
Initial drug choice depends on what type
If you give the wrong med you could induce MORE seizures
Meds for all partial seizures
Valproate**
Carbamazepine
Phenytoin
Meds for generalized tonic-clonic
Valproate**
Carbamezepine
Phenytoin
Meds for absence seizures
Valproate
Meds for myoclonic seizures
Valproate
Meds for atonic seizures
Valproate
Anti-epileptic drugs (AEDs)
Most pts respond to 1-2 AEDs
Rarely do they require more than 2
What % of pts are controlled with AED monotherapy?
50-70%
What % of pts require combination AED therapy
30%
What % of pts are poorly controlled despite AED therapy
5%
Pseudoresistance to AEDs
Wrong diagnosis
Wrong drug(s)
Wrong dose
Lifestyle issues (compliance, alcohol, drugs)
**MUST be ruled out to consider tx failure
Goals of AED therapy
Prevent seizures
Maintain normal function
Improve quality of life
**All w/ fewest side effects
Principle of AED therapy
Select recommended drug for seizure type
When augmenting AED therapy, what should you do?
Choose a drug w/ an alternative mechanism
When do you start AED therapy?
Depends on the pt
Rarely needed after single episode
Start in pts at risk for recurrent seizures
Generally start after >2 unprovoked seizures
Is AED therapy lifelong?
Not necessarily
AED withdrawal
Should be gradual/tapered
Sudden could lead to status epilepticus
When is AED relapse more likely
When withdrawn over 1-3 months
When is AED relapse less likely
If withdrawn over 6 months
What 2 standalone drugs do AEDs interact with?
Oral contraceptives
Warfarin
Significant CYP450 inducers
Phenytoin (Phenobarbital)
Carbamezepine
Primidone
Less significant CYP450 inducers
Oxycarbazepine
Topiramate
Much less significant CYP450 inducers
Newer (2nd generation) agents
Common AED side effects
Suicidal ideation (2 fold risk over general population)
CNS issues
Osteomalacia
Osteoporosis
Vision changes
Correlate drug levels to sx before changing meds
CNS side effects
Slowed thinking
Sedation
Ataxia
Dizziness
Why is AED monotherapy preferred
Increases adherence
Provides wider therapeutic index
More cost effective
Combination AED therapy guidelines
Combinations promote drug-drug interactions
No controlled studies comparing drug combos
Choose add-on w/ different MOA and/or SE profile
Big 3 AED meds
Phenytoin
Carbamezepine
Valproic acid
Phenytoin
IV or PO dosing
SE of phenytoin
Gingival hyperplasia Rash Acne Nystagmus Hirsutism Osteomalacia Folate deficiency
Carbamazepine
PO
SE: hyponatremia
Advantage = less cognitive impairment
Valproic Acid
IV and PO dosing
SE: fatal hepatotoxicity
Divalproex
Derivative of valproic acid
Depakote, Depakote ER
1:1 dimer in enteric coated tablet
Less GI effects
Phenobarbital
Rarely used except for in pregnancy More SE than other drugs Abrupt stopping may cause seizures Taper slowly Primidone -> metabolized to phenobarbitol
Benzodiazepines for seizures
Long term use not practical due to tolerance
Benzo agents for seizures
Clonazepam
Diazepam
Lorazepam
Agent for absence seizures
Ethosuximide
Felbamate
Use cautiously
Can cause fatal aplastic anemia and hepatotoxicity
Topiramate
Can cause temporary or permanent vision loss
Decreases sweating
Zonisamide
Chronic side effects similar to topiramate
Levetiracetam
Newer agent
Few drug interactions
IV and PO dosing
Gabapentin and Pregabalin
GABA analog
No interactions
Not first line AED
What AED do you give in pregnancy
Phenobarbital-D
Anticonvulsant of choice during pregnancy
Apparently this isn’t true
American Academy of Neurology stance on generic stubsitution
Opposes generic substitution of anticonvulsant drugs for tx of epilepsy w/o physician approval
What AEDs are used for neuropathic pain
Gabapentin
Pregabalin
Other uses for AEDs
Bipolar disorder
Migraine
Status Epilepticus
Life-threatening emergency
Mortality = 20%
Status etiology
AED noncompliance/discontinuation Withdrawal syndromes (alcohol/barbiturates) Brain injury (tumor/stroke) Metabolic abnormalities (decreased glucose, Na, Ca, Mg, etc.) Drug use/overdoes that lowers seizures threshold
Drugs that lower seizure threshold
Imipenem
High dose penicillin G (IV PCN)
Lidocaine
Tx of status
Diazepam Lorazepam Phenytoin Fosphenytoin Phenobarbital
Diazepam for status
Inject directly -> diluting causes precipitation
Typically provides 30-40 minute seizure free interval
(often <20 mins due to redistribution into adipose)
Advantages of lorazepam for status
More effective than phenytoin
Easier to use than diazepam + phenytoin or phenobarbitol
Lorazepam for status
Most effective in terminating seizures w/in 20 mins and maintaining seizure free state in first 60 mins after tx
Longer lasting than diazepam
May be diluted w/ equal volume of 0.8% NaCl
Phenytoin for status
15-20 mg/kg IV load (better results at higher end 18-20)
Infuse no faster than 50 mg/min (may need to slow if pt becomes hypotensive)
Fosphenytoin for status
Pro-drug of phenytoin
How is fosphenytoin dosed?
Phenytoin equivalents (PEs)
How many mgs of fosphenytoin to phenytoin?
1.5 mg fosphenytoin to 1 mg phenytoin
Can you infuse fosphenytoin faster or slower than phenytoin
Faster
150 mg/min
Advantage of fosphhenytoin
Highly water soluble so it likely won’t precipitate
Allows for IM administration
Less hypotension
Can be mixed in any solution
Phenobarbital dosing for status
If refractory:
IV 15-20 mg/kg @ 50 mg/min
Phenobarbital for status
Not 1st line due to: Slow administration
Prolonged sedation (half life 80-100 hours)
Greater risk of hypotension and hypoventilation
Little used -> not quickly available
How much folate do you supplement in young females on AEDs
1-4 mg/day
Who should you contact if you have questions about a pregnant pt on AEDs
AED Pregnancy registry
When do you discontinue AEDs?
Depends on seizure type, seizure free duration, EEG, etc.
Do you abruptly stop AEDs?
NO!!!
What does optimal AED tx require?
INDIVIDUALIZATION
% of fetal malformations w/ Levetiracetam (Keppra®)
2.4%
% of fetal malformations w/ Lamotrigine (Lamictal®)
2.0%
