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Human Disease and Therapeutics > EXAM I Epilepsy and Antiseizure Drugs > Flashcards

EXAM I Epilepsy and Antiseizure Drugs Flashcards

1
Q

when was the last forcible sterilization in the US?

A

1981 in oregon

(legalized from 1934-1981)

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2
Q

epilepsy is a neurological disorder affects what percent of the population?

A

1.2%

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3
Q

what percent of patients with epilepsy are therapy-resistance? and what is the criteria for being therapy-resistant?

A
  • 25-40%
  • therapy resistant = have failed 3 or more appropriate prescribed antiseizure drugs (ASDs)
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4
Q

what is the economic burder ($) of epilepsy?

A

>$15.5 billion annually

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5
Q

is there a need for safer and more effective epilepsy therapies?

A

yes

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6
Q

___ is a finite clinical manifestation of abnormal and excessive excitation of a population of cortical neurons

A

seizure

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7
Q

___ is a syndrome characterized by 2 or more (recurrent) seizures that are unprovoked by systemic or neurologic insults

A

epilepsy

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8
Q

___ is a sequence of events that convert normal neuronal networks into a hyperexcitable network

A

epileptogenesis

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9
Q

___ is a continuous seizure lasting more than 30 minutes or 2 or more seizures without full recovery of consciousness between them

A

status epilepticus (SE)

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10
Q

any seizure lasting longer than ___ minutes is treated clinically as SE due to the high risk of morbidity and mortality

A

5 minutes

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11
Q

over a lifetime, 1 in ___ people will be diagnosed with epilepsy

A

26

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12
Q

seizures affect ___% of the population

A

10%

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13
Q

epilepsy affects ___% of the population, and ___ Americans are diagnosed with epilepsy each year

A
  • 1% (= 1/26 people)
  • 150,000
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14
Q

put the following in order of most to least susceptible to epilepsy:

pediatric

adult

elderly

A

elderly > pediatric > adult

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15
Q

what are the 4 causes of epilepsy in pediatric patients?

A
  • genetic susceptibility
  • perinatal and neonatal insults
  • CNS infection/fever
  • trauma
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16
Q

what are the 3 causes of epilepsy in adults?

A
  • trauma
  • neonatal GEFS+
  • CNS infection/fever
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17
Q

what are the 4 causes of epilepsy in elderly patients?

A
  • neoplasms
  • stroke
  • neurodegenerative disorders
  • trauma
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18
Q

what are 10 common seizure precipitants?

A
  • metabolic and/or electrolyte imbalance
  • stimulant intoxication
  • depressant withdrawal
  • sleep deprivation
  • reduction or inadequate ASD treatment
  • hormonal variations
  • stress
  • hypoxia
  • high fever or CNS infection
  • concussion and/or closed head injury
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19
Q

what type of seizure is a single focus (focal), and the patient is fully aware and responsive?

A

simple partial seizure

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20
Q

what type of seizure is a focal onset with local spread; patient is initially aware and responsive, but may develop some memory impairment if limbic system is involved?

A

complex partial seizure

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21
Q

what type of seizure occurs when the patient is initially aware and responsive, but then loss of responsiveness and any memory as seizure then fully generalizes to involve the entire cortex, midbrain, and thalamus?

A

secondarily generalized seizure

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22
Q

what type of seizure involves loss of awareness and lack of responsiveness, generalization from onset?

A

generalized seizures

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23
Q

what are 3 types of generalized seizures?

A
  • tonic-clonic (stiffening and spasms)
  • absence
  • atonic
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24
Q

what type of seizure has the shortest duration?

A

simple partial seizures

usually <90 seconds

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25
Q

what is the phenotype of simple partial seizures?

A

depends on areas of focal cortical involvement:

  • motor cortex produces symptoms
  • somatosensory cortex produces sensory symptoms
  • occipital cortex produces visual disturbances, blurred vision, and hallucinations
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26
Q

focus/foci of simple partial seizures are confirmed via ___

A

EEG

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27
Q

complex partial seizures have a localized onset which often spreads ___ and usually has ___ involvement

A
  • bilaterally
  • limbic
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28
Q

if a complex partial seizure fully generalizes, it is called a ___

A

secondarily generalized seizure

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29
Q

the clinical manifestations of complex partial seizures varies with ___

A

site of origin and degree of spread

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30
Q

what is the duration of complex partial seizures?

A

slightly longer than simple partial seizures

usually <2 minutes

31
Q

secondarily generalized seizures may begin as either ___ or ___ seizures

A

simple or complex partial seizures

32
Q

T or F:

secondarily generalized seizure activity fully generalizes with known symmetry, intensity, and duration before evolving into tonic and/or clonic phases

A

false

symmetry, intensity, and duration are variable

33
Q

what is the duration of secondarily generalized seizures?

A

usually < 4 minutes

34
Q

what is the postictal phase of secondarily generalized seizures?

A

confusion, somnolence, with or without transient focal deficit that can last minutes to hours

35
Q

absence seizures probably represent abnormal interactions between ___ and ___ transmissions

A

cortical and thalamic

36
Q

what is the duration of impaired awareness and responsiveness of typical absence seizures?

A

2-15 seconds

37
Q

despite <40 ASDs being available for the ___ treatment of epilepsy, approx. 1/3 of all pts with epilepsy remain ___ to all pharmacological treatments clinically available

A
  • symptomatic
  • refractory
38
Q

what are some things that an ideal ASD would offer patients?

A
  • effective for their seizure type
  • wide therapeutic index (safe)
  • no organ toxicity
  • no teratogenicity
  • no drug-drug interactions
  • long half life
  • no protein binding
  • water soluble (easily absorbed)
  • no active metabolites
39
Q

___ is the safety margin between the effective and toxic dose calculated as the median toxic dose over the median effective dose at any given time

A

therapeutic index

40
Q

an ASD with a narrow therapeutic range will put the patient at increased risk of reaching ___ or ___ plasma levels

A

reaching toxic or sub-therapeutic plasma levels

41
Q

what are 3 mechanisms of action for the most commonly used ASDs?

A
  • enhancement of GABA-mediated inhibition
  • reduction of excitatory transmission (i.e. glutamate)
  • modification of ionic conductance (i.e. Na2+, Ca2+, K+)
42
Q

___ is a great drug for partial epilepsy, but the potential for drug-drug interactions is high

A

carbamazepine (tegretol)

43
Q

what are the indications of carbamazepine (tegretol)?

A
  • partial
    • simple and complex
  • generalized tonic-clonic
44
Q

what are side effects of carbamazepine (tegretol)?

A
  • common
    • blurred or double vision, cognitive impairment
  • rare
    • stevens-johnson syndrome, aplastic anemia
45
Q

carbamazepine (tegretol) should be avoided in what type of seizure?

A

absence, because it may aggravate spike-wave seizures

46
Q

the following is the mechanisms of action of what ASD?

blocks voltage-gated Na+ channels to inhibit repetitive firing in neurons

A

carbamazepine (tegretol)

47
Q

___ is a milder form of toxic epidermal necrolysis (TEN)

A

stevens-johnson syndrome

48
Q

the following are symptoms of what syndrome?

fever, sore throat, fatigue, painful lesions in the mucous membranes in the mouth and lips, spreads rapidly to face, trunk, arms, legs, and feet

A

stevens-johnson syndrome

49
Q

which patients are most at-risk for stevens-johnson syndrome?

A

patients on sodium channel blocker ASDs

50
Q

___ raises carbamazepine (CBZ) levels in plasma by inhibiting its breakdown by ___

A
  • grapefruit juice
  • CYP3A4
    • grapefruit juice inhibits CYP3A4 enzyme in the gut/liver, decreasing CBZs metabolism and increases its plasma levels
51
Q

what is the indication for ethosuximide (zarontin)?

A

uncomplicated absence seizures only

52
Q

what are common side effects of ethosuximide (zarontin)?

A
  • drowsiness, dizziness, HA, loss of appetite (minor weight loss), and GI upset
  • may worsen partial and tonic-clonic seizures
53
Q

what is the clinical spectrum and half life of ethosuximide (zarontin)?

A
  • narrow clinical spectrum - for absence seizures only
  • very long half life = 40 hours
54
Q

what is the mechanism of action of ethosuximide (zarontin)?

A

reduces t-type calcium channel currents in thalamic pacemaker neurons to quiet rhythmic spike wave discharges

55
Q

what are the indications for phenytoin (dilantin)?

A
  • partial seizures
    • simple and complex
  • generalized tonic-clonic seizures
56
Q

what is a non-dose related side effect of phenytoin (dilantin)?

A

gingival hyperplasia

57
Q

phenytoin (dilantin) has ___-order kinetics at high doses

A

zero

you want to check plasma levels often and titrate dose as needed

58
Q

what are contraindications for phenygoin (dilantin)?

A
  • absence seizures - aggravates absence spike-wave seizures
59
Q

what is the mechanism of action of phenytoin (dilantin)?

A

blocks sustained high frequency firing of APs by blockade of sodium channels during repetitive firing

60
Q

what are the indications for topiramate (topamax)?

A
  • partial seizures
    • simple and complex
  • generalized
    • tonic-clonic seizures
    • lennox-gastaut syndrome
61
Q

what are common side effects of topiramate (topamax)?

A
  • word recall problems
  • weight loss
  • open-angle glaucoma (not common, but serious)
62
Q

what ASD increases metabolism of estrogen so it can reduce oral contraceptive efficacy (must use secondary means of birth control to avoid pregnancy)?

A

topiramate (topamax)

63
Q

what is the mechanism of action of topiramate (topamax)?

A
  • broad spectrum (multiple MOA)
  • blocks repetitive firing of voltage gated sodium channels, inhibits calcium currents, inhibits AMPA/kainate receptors, and potentiates GABA currents
64
Q

what is the indications for valproic acid (depakote)?

A
  • generalized
    • absence, atypical absence, myoclonic, tonic-clonic
  • partial
    • simple and complex
65
Q

what are common side effects of valproic acid (depakote)?

A
  • weight gain
  • toxic doses: reye-like syndrome, hepatic failure
66
Q

what are the contraindications for valproic acid (depakote)?

A

patients with hepatic disease or significant hepatic dysfunction

67
Q

patients taking what ASD are at increased risk of teratogenicity and neural tube defects, such as spina bifida?

A

valproic acid (depakote)

68
Q

what is the mechanism of action of valproic acid (depakote)?

A
  • broad spectrum (multiple MOAs)
  • blocks voltage gated sodium channels (main mechanism), reduces NMDA currents, increases GABA-mediated Cl- currents
69
Q

valproate should be avoided during ___ due to teratogenicity and neural tube defects

A

pregnancy

  • category D risk for defects including spina bifida and other birth defects if taken in the 1st trimester

**valproate = valproic acid

70
Q

which ASDs are indicated for partial seizures?

A
  • carbamazepine
  • phenytoin
  • topiramate (if secondarily generalized)
71
Q

which ASDs are indicated for generalized onset tonic clonic seizures?

A
  • valproate
  • topiramate
72
Q

which ASDs are indicated for absence seizures?

A
  • ethosuximide (uncomplicated)
  • valproate (complicated)
73
Q

appropriate ASDs should be matched to the patients seizure type confirmed by ___

74
Q

in ASD treatment, ___ should be tried first

A

monotherapy (aka one drug)

Human Disease and Therapeutics (5 decks)

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