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PHRM 845 > (3.11) Pharmacotherapy of seizure disorders > Flashcards

(3.11) Pharmacotherapy of seizure disorders Flashcards

1
Q

What are risk factors for seizure reccurrence?

A
  • <2 yrs seizure free
  • Onset of seizure after age 12
  • Hx of atypical febrile seizures
  • 2-6 yrs before good seizure control in tx
  • > 30 seizures before controlled
  • Partial seizures (most common)
  • Abnormal EEG
  • Organic neurological disorder
  • Withdrawal of phenytoin or valproate
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2
Q

What is drug resistant epilepsy?

A

Failure of at least 2 trials of antiseizure meds of adequate dose and duration

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3
Q

What are possible reasons for tx failure in drug resistant epilepsy?

A
  • Failure to reach CNS target
  • Alteration of drug targets in CNS
  • Drugs missing the real target
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4
Q

What are management strategies of drug resistant epilepsy?

A
  • Rule out pseudo-resistance (wrong drug or diagnosis)
  • Combination therapy
  • Electrical/surgical intervention
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5
Q

What is status epilepticus?

A

Continuous seizure activity lasting 5 minutes or more, or two or more discrete seizures w incomplete recovery between seizures

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6
Q

What dosage form is most commonly used for status epilepticus?

A

IV

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7
Q

What is the most common drug class used for status epilepticus?

A

Benzodiazepines, most commonly lorazepam or midazolam

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8
Q

When is fosphenytoin used?

A

In the second or third treatment phase of status epilepticus

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9
Q

What is an issue with phenytoin?

A

Contains propylene glycol - can cause hypotension and this limits infusion rate

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10
Q

What is fosphenytoin?

A

Prodrug of phenytoin, better IV tolerance of dosing

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11
Q

What is the loading dose of fosphenytoin?

A
  • 20 mg PE (phenytoin equivalents)/kg IV, may give additional dose 10 minutes after load
  • Up to 150 mg PE/min IV infusion
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12
Q

What is the monitoring parameter with phenytoin/fosphenytoin?

A

Cardiac monitoring required, may also cause local rxn called “purple glove syndrome”

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13
Q

What must be obtained in the same blood draw (oral phenytoin dosing considerations)?

A

MUST obtain both phenytoin serum conc and serum albumin

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14
Q

What is the equation for adjusted conc (oral phenytoin dosing considerations)?

A
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15
Q

What is the therapeutic serum conc range (oral phenytoin dosing considerations)?

A

10-20 mcg/ml

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16
Q

What does it mean if there the unadjusted conc falls within the therapeutic range?

A

There is unbound phenytoin within the therapeutic range of 1-2 mcg/ml

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17
Q

What is the IV to PO conversion of valproate?

A

1:1 mg/mg

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18
Q

What is the desired serum concentration of valproate?

A

80 mcg/ml (range 50-125 mcg/ml)

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19
Q

Which drugs are 1A2 inducers?

A
  • Carbamazepine
  • Phenobarbital
  • Phenytoin
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20
Q

Which drugs are 2C9 inducers?

A
  • Cabamazepine
  • Phenobarbital
  • Phenytoin
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21
Q

Which drugs are 3A4 inducers?

A
  • Carbamazepine
  • Lamotrigine
  • Oxcarbazepine
  • Phenobarbital
  • Phenytoin
  • Topiramate
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22
Q

Which drug is a UGT inhibitor?

A

Valproate

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23
Q

What is the dosing of lamotrigine?

A
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24
Q

What is the black box warning prior to initiating carbamazepine or derivatives?

A

Genetic screen for HLA-B*1502 allele due to anticonvulsant hypersensitivity syndrome

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25
Q

Can HLA-B*1502 allele positive pts be treated with carbamazepines or derivatives?

A

NO unless benefit clearly outweigh the risk

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26
Q

There is a strong correlation for positive HLA-B*1502 allele and anticonvulsant hypersensitivity syndrome in ppl of what descent?

A

Asian descent

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27
Q

What other allele may confer similar risk to HLA-B*1502 and anticonvulsant hypersensitivity syndrome?

A

Positive HLA-A*3101 in those of Northern European and Asian descent

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28
Q

What is the outlook and mortality rate of DRESS syndrome?

A

Potentially life threatening - estimated mortality rate of 10%

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29
Q

When does DRESS syndrome occur?

A

Generally, occurs 2-6 wks after initiation of drug therapy

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30
Q

What drugs are associated w DRESS syndrome?

A

Carbamazepine, cenobamate, lamotrigine, phenobarbital, phenytoin, valproate, zonisamide

31
Q

Which pts have an increased risk for DRESS syndrome?

A

Pts who are positive for HLA-A*3101 allele

32
Q

What can cause antiseizure drug withdrawal syndrome?

A

Associated w abrupt d/c of antiseizure med therapy

33
Q

What can antiseizure drug withdrawal syndrome cause?

A

Recurrence of seizures, doses of antiseizure me should always be tapered for d/c

34
Q

Drug serum concentrations may be altered in pregnancy due to what?

A

Volume of distribution

35
Q

Which common antiseizure drugs are known teratogenic risks?

A

Carbamazepine, clonazepam, fosphenytoin, phenobarbital, phenytoin, primidone, topiramate

36
Q

What should pt counseling consist for ppl of child bearing age?

A

Education about these teratogenic risks in antiseizure meds and contraceptive use

37
Q

Which drug is not recommended in pregnancy no matter what and why?

A
  • Valproate
  • Due to neural tube defects and is associated w a decreased IQ in offspring
38
Q

Which supplement should be considered during pregnancy?

A

Folic acid 5 mg daily

39
Q

What should infants receive at birth to decrease risk of hemorrhagic disease?

A

Vitamin K 1 mg IM

40
Q

What are contraceptive drug interactions mediated by?

A

P450 3A4 induction - 3A4 inducer antiseizure meds will lower serum conc of estrogen contraceptives

41
Q

How can contraceptive drug interaction be minimized?

A

By using higher-dose estrogen contraceptives but warning for increased thromboembolism

42
Q

What contraceptives can be used to minimize contraceptive drug interaction?

A

Can use progestin only contraceptives:
- Depot formulation
- IUDs also recommended

43
Q

What is an interaction between estrogen and lamotrigine?

A

Estrogen can decrease lamotrigine serum conc by 50% and lamotrigine decreases estrogen conc

44
Q

What is a CV risk with lamotrigine?

A

Arrhythmia

45
Q

What are CV risks w lacosamide and pregabalin?

A

PR interval changes

46
Q

What is a CV risk w lacosamide?

A

Heart block

47
Q

What is a CV risk w phenytoin/fosphenytoin?

A

Arrhythmia

48
Q

What is a CV risk w fenfluramine?

A

Valvular heart disease

49
Q

What can carbamazepine, eslicarbazepine, oxcarbazepine cause?

A

Hyponatremia (most caused by oxcarbazepine), syndrome of inappropriate antidiuretic hormone (SIADH)

50
Q

What can phenytoin cause?

A

Altered vitamin D metabolism and decreased calcium conc leading to osteoporosis w long term use

51
Q

What can topiramate and zonisamide cause?

A
  • Decreased serum bicarb leading to metabolic acidosis
  • Nephrolithiasis so monitor serum bicarb
  • Also associated w decreased sweating, heat intolerance, oligohydrosis
52
Q

What are the psychiatric SEs of levetiracetam?

A

Psychosis, suicidal thoughts/behaviors, unusual mood changes, worsening depression

53
Q

What are the psychiatric SEs of perampanel?

A

Boxed warning: dose related serious and/or life threatening neuropsychiatric events

54
Q

What are the psychiatric SEs of valproate?

A

Acute mental status changes related to hyperammonemia; differentiate from sedation SE

55
Q

What are the psychiatric SEs of topiramate?

A

Associated w cognitive dysfunction if dose is increased too rapidly, use a slow dose titration

56
Q

What are visual risks w topiramate?

A

Post marketing warning for vision loss, myopia, retinal detachment

57
Q

What are visual risks w vigabatrin?

A

CI in pts who have other risk factors for irreversible vision loss

58
Q

What is main evaluation points of gabapentin and pregabalin?

A

Risk for respiratory depression in pts who are taking other CNS depressants, has pulmonary disease, or is elderly

59
Q

What can valproate cause?

A
  • Thrombocytopenia - monitor CBC/platelets
  • PCOS, weight gain, sedation
60
Q

When is phenytoin absorption decreased and how can this be avoided?

A
  • Decreased when given w enteral feedings
  • Hold feedings 1-2 hours before and after administration
61
Q

What are the main SEs of phenytoin?

A

Gingival hyperplasia and hirsutism

62
Q

When is zonisamide CI?

A

CI if there is a sulfa allergy

63
Q

How are gabapentin and pregabalin eliminated?

A

Renally eliminated, decrease dose in w renal impairment

64
Q

What is Lennox-Gastaut Syndrome?

A

Multiple seizure types that develop in childhood, usually accompanied by intellectual disability, sometimes responsive to combination of some AEDs

65
Q

What is Dravet Syndrome?

A

Rare genetic epileptic encephalopathy w normal childhood development until seizures begin in 1st year of life leading to multiple seizure types and developmental disability

66
Q

What is Epidiolex?

A

Cannabidiol oral solution

67
Q

What is Epidiolex used for?

A

Indicated for Dravet syndrome and lennox gastaut syndrome

68
Q

What is the keto diet?

A

3:1 or 4:1 fats:carbs/proteins

69
Q

What are SEs of keto diet?

A

Hyperlipidemia (reversible upon diet d/c), weight loss, constipation, kidney stones, decreased bone mass/growth

70
Q

How do keto diet affect adults and children?

A
  • Adults seem to respond only while on diet
  • Children may continue to see effects after diet is d/c
71
Q

What is a warning that all AEDs carry?

A

A warning for increased risk of suicidal thinking and/or behaviors during tx

72
Q

What warning does antidepressants carry?

A

Increased risk of suicidal thinking and behaviors during tx in pts <24 yo

73
Q

What is an absolute CI of bupropion?

A

Use of bupropion should be avoided in pts w uncontrolled seizure disorders, as it can increase risk of seizures and frequency

PHRM 845 (48 decks)

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