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drugs for epilepsy Flashcards

1
Q

what are the 3 general mechanisms of action for anti-epilepsy drugs?

A
  1. promote the inactivated state of voltage gated Na+ channels
  2. Pre or post synaptic enhancement of GABA medicated inhibition
  3. inhibition of T-type voltage-activated Ca2+ channels (absence seizures)
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2
Q

FDA has issued a warning of what adverse effect with the use of anticonvulsants?

A

suicidal ideation

  • 2 fold increase
  • monitor all pts for emerging depression/suicidal thoughts
  • educate pts about risks
  • use minimum drug levels for epilepsy
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3
Q

current drugs control seizures only in what percentage of pts?

A

50%

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4
Q

the adverse effects of anti epileptic drugs can have what effect on pts?

A

responsible for limited pt adherence

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5
Q

instead of adding a drug to an exisint anticonvulsant monotherapy regimen, what should you do?

A

substitute rather than additive treatment

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6
Q

MOA of carbamazepine

A

blocks voltage gated Na channels and decreases glutamate release

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7
Q

MOA of clonazepam

A

enhance GABA-A receptor responses

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8
Q

MOA ethosuximide

A

decreases T-Type Ca2+ currents (used for absence seizures)

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9
Q

MOA felbamate

A

blocks NMDA receptors; increase GABA

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10
Q

MOA gabapentin

A

blocks alpha-2 delta-1 subunit of Ca2+ channels

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11
Q

MOA of lacosamide

A

blocks Na+ channels

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12
Q

MOA lamotrigene

A

blocks Na+ channels

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13
Q

MOA oxcarbazepine

A

blocks Na+ channels, possibly increases K+ & decreases Ca2+ effects

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14
Q

MOA Phenytoin

A

blocks voltage gated Na+ channels

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15
Q

MOA pregablin

A

blocks alpha-2 delta-1 subunit of Ca2+ channel

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16
Q

MOA Topiramate

A

blocks Na+ channels; increases K+ current, increases GABA; decreases glutamate activity

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17
Q

MOA valproate

A

increases GABA activity; also decreases Na+ channnels

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18
Q

MOA zonisamide

A

blocks Na+ channels, & decreases T-type Ca2+ actions

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19
Q

the anti-epileptic drug have limited protein binding except which two drugs?

A

phenytoin & valproate

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20
Q

which antiepileptic drug accumulates in erythrocytes?

A

zonisamide

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21
Q

which type of formulation for anti-epileptic drugs promotes adherence?

A

slow release products (fewer doses / day)

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22
Q

what happens to the half-life of carbamazepine as treatment progresses?

A

the half life decreases due to an increased rate of hepatic metabolism

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23
Q

which two anti-epileptic drugs are not metabolized?

A

gabapentin & pregabalin

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24
Q

which antiepileptic drug has no CYP activity and is metabolized by uridine glucuronosyl transferasewith subsequent induction of UGT (hint its metabolites are eliminated in urine)?

A

lamotrigine

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25
which antiepileptic drug is metabolically conjugated, decreases CYP2C19& increases CYP3A4/5?
OXCARBAZEPINE
26
what is the only antiepileptic drug that is eliminated in the stool?
phenytoin
27
Phenytoin is metabolized by what CYP Enzymes?
CYP2C9>>CYP2C19
28
Routine monitoring of serum drug levels is required with what 3 drugs?
carbamazepine Phenytoin Valproate
29
what should the physician do for a pt experiencing good seizure control and no signs or symptoms of significant drug toxicity, despite serum drug levels being high?
physician doesn't have to reduce drug dose, but rather use clinical presentation to guide treatment
30
which two drugs are weak carbonic anhydrase inhibitors?
topiramate/zonisamide
31
what is the adverse effect you may predict with the weak carbonic anhydrase activity of topiramate/zonisamide therapy?
promotes stone formation by reducing urinary citrate excretion & by increasing urinary pH (monitor serum bicarbonate levels)
32
discontinuation of antiepileptic drugs can precipitate what adverse effects?
status epilepticus, increased frequency of seizures & various neurologic issues, like anxiety (remember to taper the dose rather than stop it abruptly)
33
what is the name of the phytoin prodrug?
fosphenytoin (remember dose adjustment is important when transitioning b/w the two)
34
which antiepileptic drugs has zero order elimination?
phenytoin
35
what are some of the ADME problems with phenytoin?
issues of protein binding displacement and CYP mediated drug-drug interactions - --highly variable induction of CYPs - --Age, cigarette smoking & hepatic status confounding factors
36
what is the most common CNS adverse effect of phenytoin therapy?
nystagmus
37
which antiepileptic drug can cause gingival hyperplasia?
phenytoin
38
what are some of the dermatologic adverse effects of phenytoin therapy?
usually benign-measles-like rash, SJS, TEN, & DRES | Hypertrichosis or hirsutism (generally confined to extremities but can affect the trunk and face, may be irreversible)
39
what are some of the CNS adverse effects of carbamazepine?
``` esp. during initial treatment phase dizziness drowsiness ataxia blurred vision ```
40
which antiepileptic drug has a BBW for agranulocytosis?
carbamazepine
41
the incidence of SJS while using antiepileptic drugs is higher in Asian pts because they carry which allele?
SNP change for HLAB-1502 (good idea for these pts to also avoid other structurally related anticonvulsants like phenytoin, oxcarbazepine, lamotrigene)
42
the incidende of hepatotoxicity with valproic acid is more common in what pt population?
children
43
what are some of the CNS adverse effects of valproic acid?
somnolence, dizziness
44
what are the two main hematologic adverse effects of valproic acid?
thrombocytopenia | prolonged bleeding time
45
what are the adverse effects of clonazepam?
somnolence, ataxia, dizziness, fatigue
46
what are the AEs of ethosuximide?
somnolence, dizziness, headache, N/V, Diarrhea
47
what are the BBWs for felbamate?
aplastic anemia, bone marrow suppression, hepatic disease
48
what are 3 common adverse effects of antiepileptic drugs?
sedation, dizziness, ataxia
49
what are some of the AEs of gabapentin?
somnolence, dizziness, fatigue
50
what are some of the AEs of lacosamide?
diplopia, dizziness, headache
51
what is the BBW for lamotrigine?
``` serious rash (TEN/SJS) other AEs are : dizziness, diplopia, ataxia, blurred vision, rhinitis ```
52
which antiepileptic drug has an adverse effect of causing URTIs?
levetiracetam
53
name the antiepileptic drug: AEs including-dizziness/diplopia, headache, N/V, nystagmus/somnolence/ataxia
oxcarbazepine
54
which antiepileptic drug has AEs that include ataxia/parasethesias/abnormal vision/psychomotor slowing?
topiramate
55
which antiepileptic drug has these AEs: somnolence, anorexia, dizziness?
zonisamide
56
which AED has the greatest risk of adverse outcomes in pregnancy?
valproate (cat. X)
57
which two AEDs can cause fetal hydantoin syndrome?
carbamazepine & phenytoin
58
what are the fetal abnormalities for valproate?
neural tube defects, clefts, skeletal abnormalities, developmental delay
59
name the AED with these Adverse effects: cleft lip, cleft palate
topiramte
60
name the AED with these adverse effects: inhibits dihydrofolate reductase lowering fetal folate levels. Registry data suggest increased risk for clefts
lamotrigine
61
what are the fetal abnormalities seen with phenobarbital?
clefts, cardiac anomalies, urinary tract malformations
62
what are some of the fetal abnormalities seen with phenytoin?
fetal hydantoin syndrome: craniofacial anomalies, fingernail hypoplasia, growth deficiency, developmental delay, cardiac defects, clefts
63
what are the four drugs of choice for partial, including secondarily generalized seizures?
lamotrigine carbamazepine levetiracetam oxycarbazepine
64
what are the 3 drugs of choice for primary generalized tonic-clonic seizures?
valproate lamotrigine levetiraetam
65
what are the 2 drugs of choice for absence seizures?
ethosuximide | valproate
66
what are the 3 drugs of choice for atypical absence, myoclonic, atonic seizures?
valproate lamotrigine levatiracetam
67
what are some of the predictors of mortaility for status epilepticus?
generalized seizure, increased pt age, anoxic brain injury, stroke, CNS infection or tumor, and lon duration of SE
68
what is the treatment of choice for status epilepticus?
benzodiazepines
69
what are the 3 benzodiazepines that are treatments of choice for status epilepticus?
IV lorazepam (first line for SE) IM midazolam Rectal dizepam Followed by an IV AED: (valproate, phenytoin, midazolam, levetiracetam, phenobarbital)
70
why is a benzodiazepine first line treatment for SE?
reinforcement of inhibitory effects of GABA and these drugs can be given rapidly IV
71
only ___________ will induce CYP2B6 & CYP3A4 compared to benzodizepines
phenobarbital
72
what do phenobarbital and benzodiazepines have in common?
both work on GABA receptor but at different sites BOTH have issues of dependence & withdrawal BOTH have tolerance development BOTH produce dose-related sedation
73
how are phenobarbital and benzodiazepines different?
barbiturates prolong opening time of Cl- channel (increased efficacy) Benzodiazepines shift dose-response curve for GABA (potency) -work at different sites of GABA receptor
74
which 3 AEDs have blood toxicities?
carbamazepine, felbamate, & valproate
75
name 5 AEDs that are big time teratogens?
lamotrigine, carbamazepine, phenytoin, topiramate, phenobarbital & valproate (worst one of all)
76
which drug is first line for status epilepticus?
lorazepam IV

NEUROLOGY (9 decks)

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