Ch 24 Drugs for Epilepsy Flashcards
Seizures are initiated by discharge from a group of hyperexcitable neurons, called a ___.
focus
In partial seizures, excitation undergoes limited spread from the ___.
focus to adjacent cortical areas
In generalized seizures, excitation spreads widely throughout ___.
both hemispheres of the brain
AEDs act through four basic mechanisms: __(4)__.
blockade of sodium channels,
blockade of calcium channels,
blockade of receptors for glutamate (an excitatory neurotransmitter), and
potentiation of GABA (an inhibitory neurotransmitter)
The goal in treating epilepsy is to reduce ____. Complete elimination of seizures may not be possible without causing intolerable side effects.
seizures to an extent that enables the patient to live a normal or near-normal life
AEDs can be divided into two main groups: ___
traditional AEDs and newer AEDs.
Many AEDs are selective for particular seizure types;
therefore, successful treatment depends on ___.
choosing the correct drug
Monitoring plasma drug levels can be valuable for (4), especially in patients taking more than one drug.
adjusting dosage,
monitoring adherence,
determining the cause of lost seizure control, and identifying the cause of toxicity
Nonadherence accounts for nearly ___. Promoting adherence is a priority.
half of all treatment failures
Withdrawal of AEDs must be done ___.
gradually, because abrupt withdrawal can trigger SE
Some AEDs may pose a risk of __ and
behavior.
suicidal thoughts
Most AEDs cause CNS depression, which can be deepened by concurrent use of other ___.
CNS depressants (e.g., alcohol, antihistamines, opioids, other AEDs)
Phenytoin is active against ___.
partial seizures and tonic-clonic seizures but NOT absence seizures
The capacity of the___ is limited. As a result, doses only slightly greater than those needed for therapeutic effects can push phenytoin levels into the toxic range.
liver to metabolize phenytoin
The therapeutic range for phenytoin is __.
10 to 20 mcg/mL
When phenytoin levels rise above 20 mcg/mL, CNS toxicity develops. Signs include __(5)__.
nystagmus, sedation, ataxia, diplopia, and cognitive impairment
Phenytoin causes ___ in 20% of patients
gingival hyperplasia
Rarely, phenytoin causes ___. Risk may be increased by the HLA-B*1502 gene variation, seen almost exclusively in patients of Asian descent.
severe skin reactions: StevensJohnson syndrome (SJS) or toxic epidermal necrolysis (TEN)
Like phenytoin, ___ is active against partial
seizures and tonic-clonic seizures.
carbamazepine
Because __ is better tolerated than phenytoin, it is often preferred.
carbamazepine
Carbamazepine can cause __(4)__.
To reduce the risk of serious hematologic toxicity, complete blood counts should be obtained at baseline and periodically thereafter.
leukopenia, anemia, and thrombocytopenia—and, very rarely, fatal aplastic anemia
Like phenytoin, carbamazepine can cause SJS/TEN. Risk
is clearly increased by the HLA-B*1502 gene variation.
Accordingly, the FDA recommends that ___.
Asian patients should be screened for this variant before using the drug
Valproic acid is a broad-spectrum AED, having activity
against ___.
partial seizures and most generalized seizures,
including tonic-clonic, absence, atonic, and myoclonic
seizures
Valproic acid can cause potentially fatal ___,
especially in children under 2 years old who are taking
other AEDs.
liver injury
Valproic acid can cause potentially fatal __.
pancreatitis
___ is highly teratogenic, and can reduce the IQ
of children exposed to it in utero. Accordingly, valproic
acid should not be used during pregnancy, unless it is the only AED that works.
Valproic acid
In contrast to other barbiturates, ___ is able to
suppress seizures without causing generalized CNS
depression.
phenobarbital
Phenytoin, carbamazepine, and phenobarbital induce the
synthesis of hepatic drug-metabolizing enzymes, and can
thereby accelerate ___.
inactivation of other drugs.
Inactivation of oral contraceptives and warfarin is of particular concern.
AEDs can interact with one another in complex ways,
causing their __.
blood levels to change.
Dosages must be adjusted to compensate for these interactions.
All traditional AEDs (and some newer AEDs) can harm
the __.
However, the fetus and mother are at greater risk from
uncontrolled seizures than from AEDs. Accordingly, women with major seizure disorders should continue taking AEDs throughout pregnancy.
developing fetus, especially during the first trimester
___ can be minimized by avoiding valproic acid and
by using just one AED (if possible) in the lowest effective
dosage.
Fetal risk
Initial control of generalized convulsive SE is accomplished with an __.
IV benzodiazepine—either diazepam or lorazepam.
When diazepam is used, follow-up treatment with phenytoin or fosphenytoin is essential for prolonged seizure suppression.
