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  1. What are the indications of carbamazepine?
    • Epilepsy
    • Neuralgias
    • Bipolar disorder and psychotic disorder
  2. What is the MOA of carbamazepine?
    Prevents repetitive firing of actions potentials in depolarized neurons by limiting sodium influx through sodium channels
  3. Discuss the bioavailability of carbamazepine.
    • Imediate release = 85-90%
    • Extendeded release = 90%
  4. What is the time to peak of carbamazepine?
    • Immediate release = 3-8 hours
    • Extended release = 3-12 hours
  5. Discuss the distribution of carbamazepine
    • Lipophilic (needs to pass through the BBB)
    • Vd = 0.8 - 1.9 L/kg
    • 40-90% protein bound
    • Bound to albumin and alpha-1 acid glycoprotein
  6. Discuss the metabolism of carbamazepine
    • Active metabolite = carbamazepine epoxide
    • Auto-induction (induces enzymes that are responsible for its own metabolism)
  7. How does auto-induction affect half-life?
    • shortens half-life over time
    • changes from 25-65 hours to ~12-17 hours after repeated doses over 3-5 weeks
  8. How does old age or liver disease affect elimination of carbamazepine as metabolites in urine?
    Clearance is decrased
  9. How does renal disease/dialysis affect elimination of carbamazepine as metabolites in urine?
    Clearance is not changed
  10. What is normal dosing and schedule of carbamazepine?
    • Start at 100 to 200 mg/day PO
    • Ususal dose is 200 mg PO BID
    • Increase every 3-14 days
    • Maximum dose is 1600 mg/day
  11. What is the therapeutic level of carbamazepine?
    4-12 mcg/L
  12. What are the monitoring recommendations for carbamazepine?
    • Trough levels recommended
    • Give time for auto-inductions to stabilize before adjusting based on a level
  13. What are the AE of carbamazepine?
    • diplopia
    • headache
    • dizziness
    • N/V
    • sedation
    • lethargy
    • leukopenia (without immunodeficiency --> shifts WBC to a tissue compartment)
    • rash
    • aplastic anemia
    • toxic hepatitis
    • antidiuretic effects
  14. What are the drug interactions with carbamazepine?
    • CYP450 inducers of 1A2, 2B6, 2C8, 2C9, 2C19, 3A4, and p-glycoprotein
    • Decreases the concentration of: estrogen contraceptives, dabigatran, fosphenytoin voriconizole, divalproex
  15. 32 yo female on Carbamazepine 400 mg po BID for seizure disorder. She started this dose 1 week ago.

    Trough level = 13 mcg/L, she is not experiencing any side effects. What should you do in regards to her dose/levels?
    Maintain current dose and recheck trough level in 2 weeks since autoinduction may not have started.
  16. What are the indications for Valproic acid?
    • Epilepsy
    • Bipolar disorder
    • Migraines
  17. What is the MOA for valproic acid?
    • Increases GABA function
    • Limits sustained, repetitive firing of sodium channels
    • Glutamate alterations
  18. Discuss ADME of valproic acid
    • A: >90% bioavailability, half-life 9-16 hours
    • D: Vd = 11 L/1.73m2
    • M: UDPGT-catalyzed glucuronidation, beta-oxidation, minor CYP450 metabolism (2A6, 2C9, 2C19, 2B6
    • E: metabolites unchanged in urine
  19. Discuss dosing of valproic acid
    • Initial dose = 15mg/kg PO (ususally 500mg) 1-3 x/day
    • IV loading dose = 15 mg/kg IV over 20 g/min
    • Can increase by 5-10 mg/kg weekly
    • Recommend to dose up to 60mg/kg/day
  20. What is the therapeutic range of valproic acid?
    50-150 mcg/ml
  21. What is the monitoring parameters for valproic acid?
    • Draw trough levels
    • 2-4 days after initiation, change in dose, addition of interacting medications
  22. What are the AE of valproic acid?
    • Dose related: tremor, weight gain, hair loss or thinning, menstrual irregularities
    • N/V, dyspepsia w/ immediate release formulations
    • Idiosyncratic:hepatotoxicity, thromboycytopenia, pancreatitis, polycystic ovary disease
  23. What are the drug-drug interactions with valproic acid?
    • phenytoin
    • carbamazepine
    • ethosuximide

    **will decrease serum concentrations of valproic acid**
  24. What are the indications for phenobarbital/primidone?
    • epilepsy
    • commonly 2nd or 3rd line agent for refractory seizures
  25. What is the MOA for phenobarbital?
    Enhances the effects of GABA which prolongs opening at the chloride channel at GABAA receptor, resulting in neuronal hyperpolarization
  26. What is primidone metabolized to?
  27. What is the ADME of phenobarbital/primidone?
    • A: F=100%, peak= 0.5-4 hours, half-life = 36-125 hours
    • D: Vdphenobarb=0.6-0.7 L/kg, Vdprimidone=0.43-1.1 L/kg; bimodal (first to highly perfused organs, then to all body tissues); protein binding = phenobarb 55%, primidone 80%
    • M: glucurondiation, p-hydroxylation via CYP2C9 & 2C19
    • E: hepatic metabolism, excreted unchanged in urine 20-45%, decreased in hepatic & renal impairment
  28. What is the dosing of phenobarbital?
    • Loading dose: 15-20 mg/kg ONCE
    • Maintenance dose: Adults = 1.5-2 mg/kg/day; Peds = 3-6 mg/kg/day
    • Frequency: given 2-3 x/day
    • Titration should be slow due to long half-life, long periods between dose increase
    • Kinetics are linear therefore dose & concentration should increase/decrease proportionately
  29. What is the dosing for primidone?
    • Start with 100-125mg at bedtime x 3 days
    • Increase by 100-125 mg/day every 3 days until at goal
    • With increasing dose spread to a frequency of 3-4 times/day
    • Maintenance dose: 10-25 mg/kg/day
  30. What is the therapeutic range for phenobarbital?
    15-40 mcg/ml

    Trough level recommended 2-3 weeks after initiation or change in dose
  31. Whis is the therapeutic range for primidone?
    • 5-12 mcg/ml
    • Get both primidone and phenobarbital levels
    • Trough level recommended 2-3 weeks after initiation or change in dose
  32. What are the AE of phenobarbital/primidone?
    • GI upset, ataxia, HA, confusion, folate deficiency, vitamin D deficiency, osteomalacia, megaloblastic anemia, porphyria, and skin rash
    • Adults: sedation, lethargy, cognitive impairment
    • Children & elderly: hyperactivity & agitation; can suppress cognitive development in children
    • Phenobarb concentration >60 mcg/mL = stupor & coma
  33. What are the drug interactions of phenobarbital/primidone?
    it is an enzyme inducer of the CYP 450 system, NADPH-cytochrome reductase UDPGT, and enzymes involved in glucoronic acid synthesis
  34. What drugs are decreased by phenobarbital?
    • contraceptives
    • lamotrigine
    • oxcarbazepine
    • phenytoin
    • zonisamide
  35. What drugs increase phenobarbital concentrations?
    divalproex and felbamate
  36. What supplement(s) should a patient take while on phenobarbital due to a specific deficiency that can occur?
    calcium/vitamin D supplements due to to vitamin D deficiency
  37. What indiciation is ethosuximide used?
    drug of choice for absence seizures
  38. What is the MOA for ethosuximide?
    reduces T-type calcium currents in thalamic neurons
  39. Discuss ADME of ethosuximide
    • A: F=100%; peak 3-7 hours; half-life 60 hours
    • D: NOT lipophilic; Vd= 0.7 L/kg; No protein binding; distributes to CSF and throughout body (except for fat)
    • M: No 1st pass metabolism, hydrolyzed by 3A4 mainly, further metabolite is conjugated
    • E: metabolites eliminated in urine; unchanged in urine (10-20%), clearance reduced in renal and liver disease
  40. What is the dosing for ethosuximide?
    • Maintenance: start at 15-30 mg/kg/day PO
    • Usually 750-1500 mg/day divided PO BID
    • Adjustments should be made slowly due to long half-life
  41. What is the therapeutic range for ethosuximide?
    40-100 mcg/L
  42. What is the monitoring for ethosuximide?
    Trough levels recommended
  43. What are the AE of ethosuximide?
    hiccups, N/V, abdomincal pain, anorexia, headache, dizziness, drowsiness, unsteadiness, rash, and transient leukopenia
  44. T/F: Ethosuximide does not induce or inhibit metabolism of other drugs
  45. Which anti-epileptics have long half-lives that mandate slow titration?
    • phenytoin
    • phenobarbital
    • ethosuximide
  46. Which anti-epileptics are NTI medications?
    • phenytoin
    • carbamazepine
    • ethosuximide
Card Set:
2012-05-02 15:38:11
Antiepileptics II 10

Antiepileptics II
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