EXAM I Epilepsy and Antiseizure Drugs Flashcards Preview

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

Flashcards in EXAM I Epilepsy and Antiseizure Drugs Deck (74):
1

when was the last forcible sterilization in the US?

1981 in oregon

(legalized from 1934-1981)

2

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

1.2%

3

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

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

4

what is the economic burder ($) of epilepsy?

>$15.5 billion annually

5

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

yes

6

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

seizure

7

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

epilepsy

8

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

epileptogenesis

9

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

status epilepticus (SE)

10

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

5 minutes

11

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

26

12

seizures affect ___% of the population

10%

13

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

  • 1% (= 1/26 people)
  • 150,000

14

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

pediatric

adult

elderly

elderly > pediatric > adult

15

what are the 4 causes of epilepsy in pediatric patients?

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

16

what are the 3 causes of epilepsy in adults?

  • trauma
  • neonatal GEFS+
  • CNS infection/fever

17

what are the 4 causes of epilepsy in elderly patients?

  • neoplasms
  • stroke
  • neurodegenerative disorders
  • trauma

18

what are 10 common seizure precipitants?

  • 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

19

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

simple partial seizure

20

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?

complex partial seizure

21

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?

secondarily generalized seizure

22

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

generalized seizures

23

what are 3 types of generalized seizures?

  • tonic-clonic (stiffening and spasms)
  • absence
  • atonic

24

what type of seizure has the shortest duration?

simple partial seizures

usually <90 seconds

25

what is the phenotype of simple partial seizures?

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

26

focus/foci of simple partial seizures are confirmed via ___

EEG

27

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

  • bilaterally
  • limbic

28

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

secondarily generalized seizure

29

the clinical manifestations of complex partial seizures varies with ___

site of origin and degree of spread

30

what is the duration of complex partial seizures?

slightly longer than simple partial seizures

usually <2 minutes

31

secondarily generalized seizures may begin as either ___ or ___ seizures

simple or complex partial seizures

32

T or F:

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

false

symmetry, intensity, and duration are variable

33

what is the duration of secondarily generalized seizures?

usually < 4 minutes

34

what is the postictal phase of secondarily generalized seizures?

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

35

absence seizures probably represent abnormal interactions between ___ and ___ transmissions

cortical and thalamic

36

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

2-15 seconds

37

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

  • symptomatic
  • refractory

38

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

  • 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

___ 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

therapeutic index

40

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

reaching toxic or sub-therapeutic plasma levels

41

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

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

42

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

carbamazepine (tegretol)

43

what are the indications of carbamazepine (tegretol)?

  • partial
    • simple and complex
  • generalized tonic-clonic

44

what are side effects of carbamazepine (tegretol)?

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

45

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

absence, because it may aggravate spike-wave seizures

46

the following is the mechanisms of action of what ASD?

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

carbamazepine (tegretol)

47

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

stevens-johnson syndrome

48

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

stevens-johnson syndrome

49

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

patients on sodium channel blocker ASDs

50

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

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

51

what is the indication for ethosuximide (zarontin)?

uncomplicated absence seizures only

52

what are common side effects of ethosuximide (zarontin)?

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

53

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

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

54

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

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

55

what are the indications for phenytoin (dilantin)?

  • partial seizures
    • simple and complex
  • generalized tonic-clonic seizures

56

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

gingival hyperplasia

57

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

zero

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

58

what are contraindications for phenygoin (dilantin)?

  • absence seizures - aggravates absence spike-wave seizures

59

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

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

60

what are the indications for topiramate (topamax)?

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

61

what are common side effects of topiramate (topamax)?

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

62

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

topiramate (topamax)

63

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

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

64

what is the indications for valproic acid (depakote)?

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

65

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

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

66

what are the contraindications for valproic acid (depakote)?

patients with hepatic disease or significant hepatic dysfunction

67

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

valproic acid (depakote)

68

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

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

69

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

pregnancy

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

**valproate = valproic acid

70

which ASDs are indicated for partial seizures?

  • carbamazepine
  • phenytoin
  • topiramate (if secondarily generalized)

71

which ASDs are indicated for generalized onset tonic clonic seizures?

  • valproate
  • topiramate

72

which ASDs are indicated for absence seizures?

  • ethosuximide (uncomplicated)
  • valproate (complicated)

73

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

EEG

74

in ASD treatment, ___ should be tried first 

monotherapy (aka one drug)