Therapeutics of Seizures

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Author:
alvo2234
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215300
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Therapeutics of Seizures
Updated:
2013-04-23 11:40:11
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Brian Mitchell
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Description:
PT II Exam III
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  1. which agents are not used in monotherapy
    • zonisamide
    • levetiracetam
  2. which agent is used to treat lennox-gastaut
    rufinamide
  3. agents not approved for children
    • zonisamide
    • pregablin
    • lacosamide
  4. what are the advantages of using newer anticonvulsant agents
    • better side effect profile
    • cleaner PK profile
    • less teratenogenicity
  5. approach tx if combination therapy is needed
    choose a 2nd agent that targets the type of seizure and has different MOA
  6. improper titration can lead to
    ADE and pt non adherence
  7. what factors favor a successful withdrawal
    • seizure free for 2-4 yrs
    • complete seizure control within 1 yr of onset
    • onset > 2 years < 35 yrs
    • only 1 type of seizure disorder
    • normal EEG
  8. how long should withdrawals be done over
    6 mths or longer
  9. if withdrawing and seizures occur
    restart antiepileptic
  10. therapeutic levels of Dilantin
    • 10 - 20 mcg/ml
    • 1 - 2 mcg/ml   (free)
  11. phenytoin AE
    • neurotoxic
    • cognition impairment
    • idiosyncratic - rashes, increased LFTs
    • osteopenia
  12. phenytoin unique AE
    • gingival hyperplasia
    • hirsutism
    • folate deficiency
    • acne
    • hypothyroidism
  13. Phenytoin Drug Interactions
    • Hepatic inducer and substrate
    • displaces highly protein bound drugs
    • decreases efficacy of oral contraceptives
    • folate increases clearance of phenytoin
  14. usual starting dose for phenytoin
    100 mg TID
  15. usual dosing range of phenytoin
    300 - 600 mg/day
  16. dose adjustments for phenytoin
    • level <7: increase by 100mg/day
    • level 7 - 12: increase by 50mg/day
    • level > 12: increase by 30mg/day
  17. phenytoin monitoring
    • LFTs
    • thyroid panel
    • CBC and folate
    • serum levels
    • rashes
  18. when should serum levels be checked for phenytoin
    5 - 7 days after dose change or an interacting drug is started
  19. what is screened for when monitoring rashes for a pt taking phenytoin
    HLA-B 1502 antigen
  20. tegretol therapeutic levels
    4 - 12 mcg/ml
  21. when do you obtain trough levels for tegretol
    right before taking next dose
  22. Carbamazepine AE
    • neurotoxic
    • idiosyncratic- rashes, hepatotoxicity
    • osteopenia
  23. Carbamazepine unique AE
    • agranulocytosis (black box warning)
    • hyponatremia
  24. when do you D/C carbamezepine
    if WBC is < 2500 and ANC < 1000
  25. carbamazepine DIs
    • autoinducer and hepatic inducer and substrate
    • oral contraceptives
    • valproic acid - inhibits breakdown of metabolite
  26. tegretol initial dosing
    XR 200mg BID
  27. titration of carbamazepine dosing
    increase by 200mg/day every 2 weeks to max 2400mg/day
  28. usual tegretol dosing
    400-1200mg/day
  29. Carbamazepine monitoring
    • LFTs
    • CBC
    • Na levels
    • serum levels
    • screen for HLA-B 1502 antigen in Asian pts
  30. what needs to be counseled to pt taking tegretol XR
    take with food and casings may be excreted in feces
  31. Depakote therapeutic levels
    50 - 120 mcg/ml
  32. Valproic Acid AE
    • Neurotoxic
    • idiosyncratic- rashes, hepatotoxicity, pancreatitis

    osteopenia
  33. unique AE of VPA
    • thrombocytopenia (dose related)
    • GI upset
    • wt gain
    • alopecia
    • increase ammonia
    • PCOS
  34. black box warning for VPA
    pancreatitis
  35. VPA DIs
    • can displace highly protein bound drugs
    • hepatic inhibitor and substrate
  36. VPA initial dosing
    10-15mg/kg/day
  37. VPA titration
    increase by 10-15kg/mg/day every wk to a max of 60mg/kg/day
  38. VPA monitoring
    • LFT
    • CBC
    • serum levels
    • wt
    • ammonia levels
  39. when is it especially important to monitor ammonia levels in pts taking VPA
    if they are experiencing any mental status changes
  40. lamictal AE
    • rash
    • cns folate deficiency
  41. lamictal DIs
    • inducer
    • VPA
    • oral contraceptives
  42. risk factors for severe dermatologic reactions
    • VPA with lamictal
    • initial dose too high
    • titrating lamotrigine dose too quickly
  43. tompamax unique AE
    • myopia
    • glaucoma
    • impaired cognition
    • kidney stones
    • paresthesias
    • wt loss
    • metabolic acidosis
    • hyperthermia
  44. topiramate DIs
    • other anticonvulsants
    • oral contraceptives- decreases efficacy
    • do not use with other carbonic anhydrase inhibitors
  45. topiramate monitoring
    • eye exam
    • weight
    • chem-7
  46. oxcarbazepine unique AE
    hyponatremia
  47. Trileptal DIs
    • inhibits 2C19
    • induces 3A4
    • decreases effect of oral contraceptives
    • hepatic inducers decrease concentrations of active metabolites
  48. levetiracetam unique AE
    psychiatric sx
  49. zonisamide unique AE
    • hyperthermia
    • kidney stones
    • wt loss
    • increased BUN and Scr
  50. Zonegram monitoring
    BUN and Scr
  51. effect of estrogen on seizures
    increase seizure effect (inhibit GABA)
  52. progesterone effect on seizure activity
    protective effect (increase GABA activity)
  53. what may seizure activity do before menstrual flow
    may increase because of increase estrogen
  54. agents which decrease effectiveness of oral contraceptives
    • phenytoin
    • carbamazepine
    • topamax
    • oxcarbazepine
    • phenobarbital
    • lamictal
    • rufinamide
  55. why do you alter doses for pregnant pts during 10 wks pregnancy and 4 wks post partum
    bc there is an increase clearance in antiepileptic agents
  56. which drugs are associated with heart malformations and cleft palate
    phenobarbital and phenytoin- pregnancy D
  57. which drugs are associated with spina bifida and hypospadia
    VPA and carbamazepine- pregnancy D
  58. how can many birth defects be prevented
    starting folate supplementation before conception
  59. which new agent is associated with birth defects
    topamax
  60. older antiepileptic agents are associated with what neonatal disorders? how do you correct this?
    • neonatal hemorrhage disorders
    • give vitamin K 10mg PO daily during last month of pregnancy
  61. what is status epilepticus
    seizure lasting longer than 30 min
  62. 1st line treatment for status epilepticus
    BZDs
  63. DOC for treating status epilepticus
    ativan
  64. 2nd line agents for status epilepticus
    phenytoin and fosphenytoin
  65. what do you mix phenytoin with
    NS (crystallizes with D5W)
  66. advantages of fosphenytoin for status epilepticus
    • phlebitis less common
    • can infuse faster with less risk of hypotension and arrhthmias

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