Epilepsy

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Author:
capnhue
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128272
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Epilepsy
Updated:
2012-02-11 18:44:36
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Regis University
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Epilepsy
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  1. Simple Partial Seizures
    • consciousness NOT impaired
    • motor, somatosensory, autonomic, psychic symptoms
    • Duration - 90 secs
    • Postictal symptoms - transient weakness or loss of sensation
    • unilateral
  2. Complex Partial Seizures
    • consciousness impaired
    • may have aura
    • motor, somatosensory, autonomic, psychic symptoms
    • automatisms (abnormal behavior where pt has no recollection; lip smacking, picking at clothes, fumbling, confusion)
    • Duration - 1-2 mins
    • Postictal symptoms - amnesia during seziure, confusion, sleepy
    • unilateral
  3. Secondarily Generalized Seizure
    simple or complex onset evolving to generalized tonic-clonic
  4. Generalized Tonic - Clonic Seizure
    • loss of consciousness w/o warning or preceded by myclonic jerks
    • cry
    • fall
    • tonicity
    • clonicity
    • cyanosis (blue/purple skin)
    • Duration - 1-2 mins
    • Postictal - amnesia during seziure, confusion, sleepy
    • bilateral
  5. Generalized Absence Seizure
    • rapid seizure onset, period of unresposiveness, rapid recovery
    • stare
    • eyes fluttering
    • automatisms (abnormal behavior w/ no recollection)prolonged
    • Duration - 2-15 secs
    • Postictal - amnesia during seizure, NO confusion, promptly resumes activity
  6. Lennox-Gastaut Syndrome
    • childhood epileptic encephalopathy
    • occurs in childs first 7 years of life
    • have many seizures/day including drop attacks (atonic seizures)
  7. Mycolonic jerks
    rapid brief muscle contractions or jerks occurring to bilateral face, trunk, or extremities
  8. Atonic seizures (drop attacks)
    • sudden loss of muscle tone can result in head drop or dropping of limbs, collapse or loss of posture, or slumping to ground
    • can occur without warning
  9. Epileptic spasms
    • occur in neonats and infants
    • also known as infantile spasms
  10. AED Adverse Effects
    • impaired cognition (late)
    • seizure aggravation (late)
    • depression (late)
    • aplastic anemia (late)
    • leukopenia (late)
    • megaloblastic anemia (late)
    • thrombocyopenia (late)
    • rash (early)
    • Gi discomfort (early)
    • liver failure (early)
    • pancreatitis (early)
    • hyyponatremia
    • weight gain/loss
  11. carbamazepine (CBZ) highest risk
    leukopenia (late)
  12. ethosuximide (ETS) highest risk
    Gi discomfort (early)
  13. felbamate (FBM) highest risk
    aplastic anemia (late) - bone marrow does not produce sufficient RBC
  14. oxcarbazepine (OXC) highest risk
    hyponatremia
  15. pregabalin (PGN, PGB) highest risk
    weight gain
  16. phenobarbital (PHB) highest risk
    impaired cognition (late)
  17. valporic acid (VPA) highest risk
    thrombocytopenia (late)
  18. neuropharmacologic mechanisms which AED drugs decrease seizure activity
    • enhancement of inhibitory neurotransmission (GABAergic)
    • inhibition of excitatory neurotransmission (usually counteracting the effects of glutamate)
    • modification of ion conduction involved in neuron action potential generation (usually affecting voltage gated sodium or calcium channels)
  19. Newer AED benefits compared to older AEDs
    • improved adverse effect profile
    • little to no need for theraputic drug moitoring (TDM)
    • less risk for pharmacokinetic drug-drug interactions
  20. most common adverse effects of AEDs
    • somnolence and difficulty concentrating occurring after initial dose and gradually improves over weeks
    • dose-related ataxia (lack of muscle coordination), diplopia (double vision), and dizziness
    • hypersensitivity (may lead to Stevens Johnson syndrome/toxic epidermal necrolysis); begins as rash then leads into hypersensitivity
  21. Valporic Acid (VPA) mechanisms of action
    • prolongs the fast-inactivated state of sodium channels, delaying repolarization of VGSCs
    • reduces T-type calcium currents, providing a reason for its efficacy in management of absence seizures
    • has a GABAergic effect, suggesting VPA enhances synthesis of GABA and inhibit the breakdown of GABA that is catalyzed by GABA-transaminase
  22. Common causes of seizures
  23. Phenytoin adverse effects
    • gingival hyperplasia
    • hirsutism (unusual hair growth for women)
    • nystagmus (involuntary eye movement)
    • blood conc > 20: ataxia, nystagmus, diplopia, vertigo
    • blood conc >30: cardiovascular collapse and death
    • teratogenic (pregnancy category D)
  24. Blocks VGSCs in fast inactivated state (delaying repolarization of VGSC)
    CBZ, LTG, OXC, PHT, TPM, VPA, ZNS
  25. Inhibits low threshold Ca currents, characterisitc of absence seizure
    ETS, LTG, VPA, ZNS
  26. Enhances GABA activity
    FBM, PHB (diminishes glutamate activity), VPA
  27. Blockade of GABA reuptake
    TGB
  28. Enahnces postsynaptic GABAA receptor currents
    TPM
  29. Rufinamide (RFM)
    • adjunctive treatment for LGS
    • MOA: not really known, maybe prlong inactivated VGSC
  30. Ethosuximide (ETS)
    • ONLY effective for absence seizures
    • MOA: reduces low-threshold T-type calcium currents in thalamus
  31. Zonisamide (ZNS)
    • adjunctive therapy for refractory partial seizures
    • contains a sulfonamide: black box warning for allergy to sulfa
    • MOA: prolongs inactivated state by blocking VGSC, and reduces threshold of T-type calcium currents
  32. Lacosamide (LCM)
    • adjunctive therapy for refractory seizures
    • MOA: Enhances transition from fact-activated to slow-activated state of the VGSC
  33. Topiramate (TPM)
    • First line treatment for newly diagonsed and refractory partial, and generalized tonic-clonic
    • MOA: 1) prolongs fast-inactivated VGSC, 2) enahnces postsynaptic GABA receptor currents, 3) limits activation of glutamate receptors
  34. Felbamate (FBM)
    • last line of therapy
    • MOA: enhances GABA activity and inhibits glutamate activity (both uknownmechanisms)
  35. Levetiracetam (LEV)
    • adjunctive therapy for refractory partial seizures
    • MOA: modifies synaptic release of GABA and/or glutamate interaction with SV2A
  36. Gabapentin (GBP), Pregabalin (PGB?PGN)
    • adjunctive therapy for partial seizures
    • MOA: mostly unkown, may increase brain GABA and inhibit glutamate activity
  37. Corrected Phenytoin Equation
    • normalized PHT levels = Measured PHT levels / (X *Albumin) + 0.1
    • X =
    • 0.1 for severe renal impairment CrCl ≤10 mL/min with hypoalbuminemi
    • 0.2 for hypoalbuminemia
    • 0.25 for elderly nursing home patients or critically ill trauma patients with hypoalbuminemia
  38. Partial Seizure (simple, complex, secondary generalized) therapy
    • First line: CBZ, OXC, GBP, PGN (PGB), TPM, VPA, LTG
    • Second line: LTG, OXC, TPM
  39. Generalized Absence Seizure therapy
    • First line: LTG, ETS, VPA
    • Second line: LTG
  40. Generalized Tonic-Clonic therapy
    • First line: TPM, VPA
    • Second line: LTG, TPM
  41. Juvenile Myoclonic Epilepsy therapy
    • First line: VPA
    • Second line: LEV, TPM, ZNS
  42. Lennox-Gastuat Syndrome (LGS) therapy
    • First line: LTG, TPM, VPA
    • Second line: FBM, RFM
  43. Children w/epilepsy
    • 2-3yrs of age: have decresed renal elminiation and heaptic activity therefore should get lower dose
    • 3yrs or older: should increse dose due to incresed hepatic activity
    • febrile seizures: treat with rectal diazepam
  44. Pregnancy
    • Oral contraceptives: Inducing AEDs (CBZ, PHB, PHT) causing less effective birth control
    • Congenital malformation: VPA, CPZ, PHB, LTG (LTG lowest risk but highest in cleft defects)
  45. Depression
    Avoid these drugs b/c they can contribute to depression: PHT, PHB
  46. Nonpharmco therapy
    • Keotgenic diet: an intial fasting state followed by high fat and low carb used to treat LGS patients
    • Surgery: temporal lobectomy
    • Vagal nerve stimulation: pacemaker-device disperses energy to wide areas of the brain
  47. Status Epilectus
    • seizure lasting more than 5 mins or recurrent seizures without regaining consciousness
    • occurs to pts <1 or >60yrs
    • causes: febrile seizures, viral or CNS infection, pyridoxine defiency, acute encephalopathy, metabolic disorders
  48. Status Epilepticus treatments
    • IV route only
    • First line: Lorazepam perferred (diazepam or midazolam) and Phenytoin or fosphenytoin (hydantoins)
    • IV lorazepam 4mg for adulta
    • IV phenytoin 20-30mg/kg for 50mg/min for adults

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