Neuro 5 Flashcards
drugs used to tx generalized seizures are determined by ________________
the seizure subtype
therapeutic strategy for tx of seizures (/ recommendation)
- use of single drug preferred 2. multiple drugs can be used simultaneously for pts with hard to control seizures 3. thepaeutic index for most anti-seizure meds is low 4. avoid abrupt withdrawal 5. newer drugs (after 1990) have broader spectrum of activity and many are well tolerated
T/F: increased seizure frequency and/or severity can occur with accidental or purposeful withdrawal of anti-seziure meds
TRUE
when is a trial of gradual discontinuation of anti-seizure medications appropriate
when seizure free x3-4 years
in general, anti-seizure medications are well absorbed with about ____________% reaching circulation
80-100%
general anti-seizure drug kinetics
- well absorbed 2. not highly protein bound 3. cleared via hepatic mechanisms 4. converted to active metabolites (CYP450 inducers) 5. plasma clearance is slow
which anti-seizure drugs are highly protein bound?
- phenytoin (dilantin) 2. tiagabine (gabatril) 3. valproic acid
phenytoin is used for what types of seizures
partial and generalized tonic-clonic
what is the IV form of phenytoin
fostphenytoin
what is the prodrug of phenytoin
fosphenytoin
phenytoin will decrease the synaptic release of _______________, while increasing the synaptic release of ___________________
gluatmate; GABA
at therapeutic levels the major action of phenytoin is to ?
block Na channels (pre-synaptic glutamate) and inhibit the generation of rapidly repetitive AP
fosphenytoin is a _____________________ compound that is rapidly converted to phenytoin in the plasma
phosphate ester
oral absorption of phenytoin
100%
___________________ is highly protein bound anti-seizure medication, and accumulates in the brain, liver, muscle, and fat
phenytoin
phenytoin is excreted via ____________________
urine
elimination of phenytoin is ___________________, via ______________ order kinetics
dose dependent; first
what is the 1/2 life of phenytoin
12-36 hours; with 24 hours being average for most pts
how long does it take for phenytoin levels to reach a steady state after each dose change
5-7 days (4 half-lives)
a dose change, at high level doses of phenytoin, could take up to ______________ before med reaches a steady state
4-6 wks
s/sx of phenytoin toxicity
- nystagmus 2. diplopia 3. ataxia 4. gingival hyperplasia 5. sedation 6. hirsutism
what are early sx of phenytoin toxicity
- nystagmus 2. loss of smooth extra-ocular movements
T/F: if pt on phenytoin starts showing nystagmus and loss of smooth extraocular movments you should decrease the dose
false; these are early signs of toxicity, but not indicators that dose needs to be decreased
long term use of phenytoin can lead to
- coarsening of facial features 2. mild peripheral neuropathy 3. osteomalacia 4. vitamin D deficiencies 5. low folate levels 6. megoblasic anemia
what are 2 common s/e of phenytoin that would indicated dose adjustment is needed?
diplopia and ataxia
carbmazepine peak absorption is around _______________
6-8 hours
carbamazepine 1/2 life
8-12 hours in tx patients; 36 h in normal subjects
what type of seizures does carbamazepine tx
- generalized tonic clonic seizures 2. partial seizures
s/e carbamazepine
- nausea 2. diplopia 3. ataxia 4. hyponatremia 5. HA
MOA of valproate
- blocks high frequency firing of neurons 2. modified amino acid metabolism
1/2 life of valproate
9-16 hours
what types of seizures will valproate tx
- generalized tonic clonic 2. partial 3. generalized 4. absence 5. myoclonic
s/e (toxicity) of valproate
- nausea 2. tremor 3. weight gain 4. hair loss 5. hepatotoxic 6. teratogenic
MOA of lamotrigine
- blocks VG sodium channels 2. acts on VG Ca channels (presynaptically) both actions decrease release of glutamate
1/2 life of lamotrigine
25-35 hours
what types of seizures can lamotrigine tx
- generalized tonic clonic seizures 2. generalized seizures 3. partial seizures 4. absence seizures
s/e (toxicity) of lamotrigine
- dizziness 2. HA 3. diplopia 4. rash
MOA of levetiracetam
binds to synaptic vesicle protein SV2A (prevents the expulsion of gluatmate into synapse)
levetiracetam is metabolized to _________ inactive metabolites
3
1/2 life of levetiracetam
6-11 hours
what types of seizures will levetiracetam tx
- generalized Tonic clonic 2. partial 3. generalized
s/e (toxicity) of levetiracetam
- nervousness 2. dizziness 3. depression 4. seizures
MOA of topiramate
multiple actions on synaptic fx probably via actions on phsophorylation
____________% of topiramate is excreted into the urine unchanged
40%
1/2 life of topiramate
20 h, but decreases with concomitant drugs
what types of seizures will topiramate tx
- generalized tonic clonic 2. partial 3. generalized 4. absence 5. migraine
s/e of topiramate
- somnolence 2. cognitive slowing 3. confusion 4. paresthesia
all neuro meds except which class are CYP450 inducers
anti-depressants
____________________ are anti-psychotic drugs that produce high incidence of extra-pyramidal s/e at clinically effective doses
neuroleptic (“typical”)
what are examples of neuroleptic (“typical”) anti-psychotics
- phenothiazines: chlorpromazine 2. haloperiodl
