Neuro-Epilepsy II

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Author:
seyang
ID:
201736
Filename:
Neuro-Epilepsy II
Updated:
2013-02-20 20:59:40
Tags:
pharmacy
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Description:
Drugs for seizures
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  1. What are the different mechanism of action of AED?
    • - affects Na, K, Ca ions
    • -augmentation in inhibitory neurotrasmission by increasing CNS concentrations of GABA
    • -Decrease excitatory neurotransmission by decreasing glutamate and aspartate neurotransmission
  2. What are some adverse effects of AED?
    • Acute effects can be dose/serum concentration related or idiosyncratic
    • Concentration dependent effects are common but not life threatening
    • Neurotoxic ADE common
    • Idiosyncratic SDE
    • ADE can occur despite being within therapeutic range
  3. What are examples of Neurotoxic ADE?
    sedation, dizziness, blurred vision, difficulty with concentration, ataxia
  4. What are examples of Idiosyncratic SDE?
    • Idiosyncratic SDE can range from allergic rxn or they can be more severe hypersensitivity reactions
    • If acute organ failure occurs, it will occur within first 6 months of tx
  5. What are first line agents for Focal Seizures?
    • Carbamazepine
    • Phenytoin
    • Lamotrigine
    • Valproic Acid
    • Oxcarbazepine
  6. What are first line agents for absence seizures?
    Valproic acid, ethosuximide
  7. What are first line agents for myoclonic seizures?
    Valproic acid, clonazepam
  8. What are first line agents for tonic-clonic seizures?
    Phenytoin, carbamazepine, valproic acid
  9. What is carbamazepine first line agent for?
    partial and tonic-clonic seizures
  10. What is the MOA of carbamazepine?
    Inhibition of voltage gated sodium channels
  11. Where is carbamazepine metabolized?
    • Metabolized primarily by CYP3A4 in the liver
    • active metabolite is carbamazepine-10, 11-epoxide
    • has anticonvulsant activity
  12. Which AED is an autoinducer?
    Carbamazepine is an autoinducer (induces its own metabolism)
  13. What is special about carbamazepine being an autoinducer?
    • decreased half-life after chronic tx
    • begin 3 to 5 days of the initiation of tx
    • takes 21 to 28 days to complete
  14. What is the therapeutic range for carbamazepine?
    6 to 12 mcg/mL
  15. What may occur if there is the presence of the HLA-B*1502 allele?
    • Increased risk for serious skin reactions (stevens johnson syndrome and toxic epidermal necrolysis)
    • Seen in Asians
  16. What is the adult dose for carbamazepine?
    • 400-1200 mg/day
    • Critically ill patients need a loading dose
  17. What are some drug interactions with carbamazepine?
    • interact with other meds by inducing their metabolism
    • Valproic acid increases the 10-11epoxide concentrations w/o affecting the carbamazepine concentrations
    • CYP3A4 metabolism
  18. What are some adverse effects of Carbamazepine?
    Hyponatremia (increased in elderly), drowsiness, lethargy, diplopia, blurred vision, HA, ataxia, nystagmus, Stevens-Johnson Syndrome, agranulocytosis, aplastic anemia
  19. What is a potentially fatal blood cell abnormality with Carbamazepine?
    • Leukopenia: most common
    • rare reaction that responds to d/c
    • Discontinue if WBC <2500/mm3 or ANC <1000/mm3
  20. What is the first line treatment for absence seizures?
    Ethosuximide

    Dosing: 500-1000 mg BID (max 1500 mg BID)
  21. What is the therapeutic range of Ethosuximide?
    40-100 mcg/mL
  22. What is the MOA of Ethosuximide?
    inhibition of T-type calcium channels
  23. What type of metabolism can Ethosuximide exhibit?
    May exhibit nonlinear metabolism at high doses
  24. What is the MOA of phenobarbital?
    elevate seizure threshold by decreasing post synaptic excitation by stimulating post synaptic GABA receptors
  25. What is the therapeutic range for Phenobarbital?
    10-40 mcg/mL
  26. What is the dose for Phenobarbital?
    • 1-3 mg/kg/day
    • or 50-100 mg 2-3 times/day
    • dosed once daily before bedtime to minimize sedation
  27. What are some side effects of phenobarbital?
    rash, sedation, ataxia, depression, depenance
  28. What is phenobabital the drug of choice for?
    neonatal seizures
  29. What is phenytoin first line AED for?
    generalized seizures and partial seizures
  30. What is the MOA for phenytoin?
    stabilizes neuronal membranes by decreasing sodium influx/increasing sodium efflux through voltage gated dep. sodium channel blockade
  31. Which CYP enzymes metabolize Phenytoin?
    CYP2D9 and CYP2D19
  32. What type of pharmacokinetics does phenytoin exhibit?
    Michaelis-Menten

    -small dose changes results in large serum concentration changes

    metabolism dec with age
  33. Is phenytoin highly protein bound?
    Yes, >90%

    • competes for albumin sites with other drugs
    • know patient's albumin level with interpreting serum concentrations
    • significant renal dysfunction alters protein binding
  34. What is the therapeutic range for phenytoin?
    • total phenytoin 10-20 mcg/mL
    • Free phenytoin 1-2 mcg/mL
  35. What is the inital phenytoin dose?
    5 mg/kg/day divided 1-3 times/day
  36. What happens if there is the HLA-B*1502 allele present in patients taking phenytoin?
    • increase risk for serious skin rxn
    • steven johnsons syndrom
    • seen in asian descent
  37. Drug interactions with phenytoin?
    • potent CYP inducer
    • other meds can inhibit or induce phenytoin metabolisn
    • FOLIC ACID replacement enhances phenytoin clearance
  38. What are some ADE with phenytoin?
    • vit D def
    • confusion
    • slurred speech
    • ataxia
    • rash
    • nystagmus

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