Zusammenfassung der Ressource
Antiseizure Pharmacotherapy
- General concepts
- Depends on signs
presented by patient
- Low initial dose that is gradually
increased until control is achieved or
side effects prevent further increase.
- Serum drug levels
may be obtained
- If seizures continue, a
different medication is
added in small dose
increments while the dose
of the first drug is slowly
reduced.
- Meds are
discontinued over
6-12 weeks
- Newer antiseizure meds
exhibit fewer troublesome
side effects
- Limited induction of
drug-metabolizing enzymes
- Pharmacokinetic
profile less
complicated
- Generally well-tolerated
- Less of a health risk in pregnancy
- Many of the popular drugs
have found to double the
risk of suicidal ideation in
mentally ill patients
- Both newer and older drugs can cause this
- Some antiseizure drug
combos can increase
incidence of seizures
- Directed at controlling
the movement of
electrolytes across
neuronal membranes
or affecting
neurotransmitter
balance
- Antagonism of the
excitatory
neurotransmitter
glutamate.
- Glutamate works w/
Na+-K+ ATPase pump
- Blocking it indirectly prevents an influx
of positive ions into cells
- Taurine can antagonize
glutamate
- Stabilizes neuronal cell membranes by
reducing glutamate-induce + ion influx
- Drugs that potentiate GABA
- Mimic effects of GABA
by stimulating influx of
chloride ions through
GABA receptor channel
- May enhance GABA
release, block ruptake of
GABA into nerve cells, or
block GABA-degrading
enzymes
- These drugs are also used
for depression, migraines,
neuropathic pain,
postherpetic neuralgia,
dibromyalgia, spinal cord
injury, anxiety and bipolar.
- Barbiturates
- Intensifies effects of
GABA in brain
- Works against all seizures
except absence
- Low margin of safety,
high potential for
dependence,
profound CNS
depression.
- Phenobarbital:
- Can suppress optimal
neuronal discharges w/o
causing sedation.
- Inexpensive, long lasting,
low incidence of adverse
effects.
- Several weeks may be
needed for optimal effects.
- Sometimes preferred for
neonatal seizures
- Primidone (Mysoline)
- Potentiates GABA action
- Similar pharmacolgic
profile to
phenobarbital
- Although not frequent, it
can terminate status
epilepticus
- Benzodiazepines
- Bind directly to
GABA receptor
- Indicated for
absence and
myoclonic seizures
- Diazepam (Valium)
and lorazepam
(Ativan) are used to
terminal status
epilepticus.
- Tolerance may develop.
so dose needs to be
readjusted
- Generally used in
conjunction w/other
antiseizure drugs
- Drugs that suppress sodium influx
- Sodium channels are
desensitized because complete
blocking will cause death
- Other drugs will affect threshold
of neuronal firing, or may
interfere w/transduction of
glutamate
- Hydantons & Related
Durgs
- Phenytoin (Dilantin)
- Treats all types
except absence
seizures
- Seizure suppression
w/o abuse potential
or CNS depression
- Dosages highly
indiidualized
- Narrow range between
therapeutic and toxic
- Valproic acid
(Depakene)
- Preferred ftor
absence & myoclonic
seizures.
- Phenytoin-Like Drugs
- Carbamazepine (Tegretol)
- Fewer adverse
effects than other
phenytoin-related
drugs
- Perferred for
tonic-clonic and partial
seizures
- Oxcarbazepine
(Oxtellar
XR/Trilepral)
- Derivative of
carbamazepine, so
treatment profile is
similar
- Slightly better
tolerated, though
serious skin & organ
hypersensitivity have
been seen,
- Lamotrigine (Lamictal
- First-line drugs for
partial, absence, and
tonic-clonic seizures
- Also approved for
bipolar
- Duration of action
affected by other
drugs that change
hepatic metabolism.
- Levetiracetam (Keppra) & zonisamide (Zonegran)
- Adjunctive therapy
of partial seizures
in adults
- Levetiracetam is
generally less reactive
and has less adverse
effects than other
antiseizure
- Valproic acid derivatives,
lamotrigine, felbamate,
topiramate, and
rufinamide are used for
Lennox-Gastaut syndrome.
- Drugs that suppress calcium influx
- Succinimides
- Raise seizure threshold by delaying
entry of calcium into ions
- Ethosuximide (Zarontin)
- Preferred choice for absence seizures
- Amino Acid compounds
- Suppress positive ion influxes
differently from other antiseizure meds
- Effective for paroxysmal and the
psychopatholigic component of
epilepsy.
- Acetazolamide (Diamox) &
lacosamide (Vimpat)
- Restore ionic, and thus
neurologic, imbalances similar
to natural amino acids
- Acetazolmide can treat absence
and myoclonic seizures
- Also used for glaucoma, altitude
sickness, nausea, dizziness,
drowsiness, and fatigue
- Carbonic anhydrase inhibitor
- Lacosamide is chemically r/t
serine
- Does not produce
effects through
voltage-gated sodium
channels, but other
membrane protein
channels are involved
- Used in combo
w/other drugs
to treat adult
patients
w/partial onset
seizurs
- Drawbacks include
allergies, drowsiness,
dizziness, irregular
heartbeat. and
coordination
problems