Pharmacology Exam 4

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Rx2013
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49379
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Pharmacology Exam 4
Updated:
2010-11-14 02:09:59
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Seizure Epilepsy
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Seizure and Epilepsy
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  1. a transient alteration of behavior due to the disordered, synchronous and rhythmic firing of population of brain neurons
    Seizure
  2. A disorder of brain function characterized by the periodic and unpredictable occurrence of seizures
    epilepsy
  3. non-epileptic seizures
    occurred in a normal brain by treatments
  4. epileptic seizures
    evoked without evident provocation
  5. repeated epileptic seizures persist for a long period of occur so frequently that there is no recovery between attacks
    status epilepticus
  6. proposed mechanism for antiepileptic drugs
    • blocking the ability of neuronal cells to fire at high frequency
    • act on sodium or calcium channels
  7. antiepileptics acting on sodium channels
    • phenytoin
    • carbamazepine
    • valproate
  8. antiepileptics acting on calcium channels
    • low threshold (T-type) current reduction
    • ethosuximide
    • valproate
    • diazepam
    • barbiturates
  9. mechanisms to enhance inhibitory pathways
    • activation of GABAa receptor
    • inhibition of GABA transaminase (degrades GABA)
    • inhibition of GABA transporter GAT-1 to reduce neuronal and glial uptake of GABA
  10. activation of GABA
    BDZs and Barbiturates
  11. inhibition of GABA transaminase
    vigabatrin
  12. inhibition of GABA transporter GAT 1
    tiagabine
  13. block NMDA receptor
    valproate
  14. pharmacological effects of phenytoin
    • inhibits repetitive action potentials by alternating Na, K and Ca conductance
    • decrease glutamate release
    • enhances GABA release
    • no CNS depression
    • no elevation of seizure threshold
  15. Drug metabolism of phenytoin
    • good GI absorption
    • highly protein bound
    • metabolized by CYP
  16. side effects and toxicity of phenytoin
    • gingival hyperplasia
    • gi disturbance
    • cardiac arrhythmias
    • hirsutism
    • osteomalacia (abnormal vitamin D metabolism)
  17. isoniazid and cimetidine
    inhibit phenytoin metabolism
  18. phenobarbiturate
    increases phenytoin metabolism
  19. Diphenylhydantion. phenytoin (dilantin) uses
    • effective against partial seizures and generalized tonic-clonic seizures (grand mal)
    • alternative for status epilepticus
  20. Phenobarbital
    oldest anti-epileptic drug
  21. pharmacological effects of phenobarb
    • anticonvulsant effects at doses below hypnosis
    • suppress spread of seizure activity, but raise seizure threshold
  22. Phenytoin pharmacological effects
    glutamate release and AMPA receptor blockate
  23. metabolism of phenobarbital
    • oral absorption is slow
    • bound to plasma protein
  24. side effects and toxicity of phenobarbital
    • sedation
    • tolerance/dependance
    • hepatic toxicity
    • osteomalacia
    • drug interactions
  25. phenobarb used for these types of seizures
    • tonic-clonic
    • myoclonic
    • NOT petit mal
    • used in neonates, infants and children
    • not recommended in pregnancy
    • used in status epilepticus as an alternative
  26. Primidone
    • metabolized to phenobarbital
    • similar action as phenytoin
    • toxicity limits use
    • used as monotherapy for grand mal patients who fail to respond to phenytoin or phenobarb
  27. Carbamazepine
    • tricyclic structure
    • similar mechanism as phenytoin (block Na channels and inhibits high frequency repetitive firing)
    • acts presynaptically
    • complete metabolism
    • induction of CYP enzymes
  28. common side effects of carbamazepine
    • diplopia
    • ataxia
    • GI upset
  29. clinical uses for carbamazepine
    • monotherapy for grand mal and partial seizures
    • primary drug for trigeminal neuralgia
    • bipolar depression when lithium is not effective
  30. Ethosuximide
    • raises threshold for seizures
    • reduces low threshold Ca2+ currents (T Currents) in neurons
    • GI disturbances
    • Stevens-johnosn syndrome
  31. Clinical uses of ethosuximide
    • monotherapy drug of choice for absence seizures (petit mal)
    • highly effective and safe
    • polytherapy with carbamazepine or phenytoin for mixed seizures
  32. Valproic acid or valproate
    • blocks high frequency firing
    • decreases Na current
    • blocks NMDA mediated excitation
    • GAT1 inhibition
    • GAD facilitation
    • inhibits GABA transaminase
  33. Drug interactions with valproic acid or valproate
    • displaces phenytoin
    • inhibits metabolism of phenytoin, carbamazepine and phenobarb
    • decreases lamotrigine clearance
  34. Side effects with valproic acid and valproate
    • n/v & gi distress
    • weight gain
    • alopecia
  35. anticonvulsant uses of valproic acid and valproate
    • very effective for absence seizures
    • generalized absence, tonic-clonic and myoclonic seizures
    • monotherapy for mixed seizure
    • used for bipolar depression if Li does not work
    • migrane prophylaxis
  36. clonazepam used for these seizure types
    • petit mal
    • myoclonic
    • one of the most potent antiseizure agents known
  37. diazepam used for these
    • status epilepticus (iv)
    • prophylaxis of febrile seizures
  38. lorazepam used for these
    status epilepticus
  39. chlorazepate used for
    • acute alcohol withdrawl
    • adjunctive therapy for complex partial seizures
  40. Acetazolamide
    • diuretic and carbonic anhydrase inhibitor
    • all types of seizures, limited monotherapy use
  41. Gabapentin
    • GABA analog but does not stimulate GABA receptors
    • promotes release, reuptake and metabolism of endogenous GABA
  42. uses of Gabapentin
    • ajunct for poly therapy of partial seizures and generalized tonic-clonic seizures
    • neuropathic pain
    • excreted in unchanged form in urine
  43. Lamotrigine
    • blocks Na channels
    • decreases glutamate release
    • adjung therapy for partial seizures or bipolar
    • life-threatening dermatitis
  44. Vigabatrin
    • irreversibel GABA aminotransferase inhibitor
    • partial seizures and infantile spasms
    • irreversible visual field defect
  45. Tiagabine
    • inhibits GABA transporter (reuptake)
    • used as adjunct for partial seizures in adults
  46. Topiramate
    • blocks NA channels
    • potentiates inhibitory effects of GABA
    • inhibits excitatory action of kainate on AMPA
    • used for partial and primary generalized tonic-clonic adjunct
    • teratogenic in animals
  47. Zonisamide
    • sulfonamide derivative
    • inhibits NA channels and T-type Ca++ channels
    • adjucnt for partial seizures
  48. simple partial seizures
    • carbamazepine
    • phenytoin
    • valproate
  49. complex partial seizures
    • carbamazepine
    • phenytoin
    • valproate
  50. Partial seizures with secondary generalized
    • carbamazepine
    • phenobarbital
    • phenytoin
    • primidone
    • valproate
  51. Absence seizures (petit mal)
    • ethosuximide
    • valproate
    • clonazepam
  52. Myoclonic seizures
    • valprotate
    • clonazepam
  53. tonic-clonic seiszures (grand mal)
    • carbamazepine
    • phenobarb
    • phenytoin
    • primidone
    • valproate

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