neuro quiz 3-schizo

  1. nigrostiatal function
    extrapyramidal system, movement
  2. nigrostiatal DA antagonist effect
    movement disorders
  3. mesolimbi fxn
    extra dopa can inc pos sx, arousal, memory, stimulus, processsing, motivational behavior
  4. mesolimbic DA antagonist effect
    relief of psychosis (pos sx)
  5. mesocortical fxn
    cognition, communication, social fxn, response to stress
  6. mesocortical DA antagonist effect
    relief of psychosis, akathesia? worsening of neg symptoms
  7. tuberoinfundibular fxn
    regulates prolactin release
  8. tuberoinfundibular DA antag effects
    increased prolactin concentration
  9. amt of desired dopa blockage and amt assoc with abnormal movements
    60-65%, >77%
  10. in addition FGAs block DA (via D2 receptors) and:
    alpha1, H1 and cholinergic
  11. high potency FGAs, ex and side effects
    haloperidol, fluphenazine, higher D2 receptor binding affinity, greater potentialfor causing EPS side effects and prolactin elevation
  12. low potency FGAs- ex and side effects
    chlorpromazine, lower D2 receptor binding affinity (but greater affinity for H1, M1, and alpha1, greater potential for causing antihistaminic and anticholinergic side effects as well as orthostatic hypotension vs. high potency agents
  13. SGAs reverse dopamine blockade by
    5-HT blockade, reverses in mesocortical, nigrostriatal and tuberoinfundibular pathways
  14. QT prolongation, other EKG changes
    thioridazine=highest risk, SGAs thought to have lower risk than FGAs but recent studies have shown similar with SGAs
  15. anticholinergic SEs, FGAs & SGAs
    • FGA: low potency agents > than high potency
    • SGA: varies
  16. DA blockade in tuberoinfundibular pathway leads to:
    prolactin elevation, gynecomastia, galactorrhea, sexual dysfxn, amenorrhea, SGAs have LOWER risk than FGAs
  17. EPS
    due to imbalance of DA and ACh in nigrostriatal pathway, are dose related, SGAs tend to have lower risk than FGAs (higher potency FGAs>than lower potency FGAs)
  18. acute dystonia
    spasmodic or sustained muscle spasm and abnormal posture (often painful), usually neck up, tx with ACh (benztropine, diphen, etc and can use prophylactically, +- IM benzo
  19. akathisia
    severe motor restlessness and anxiety (feeling of need to move, restless legs, rocking, agitation), occurs in 20-0%, onset is days to weeks, tx with BB-propran, low dose, ACh drug, benzo, BB have best evidence
  20. pseudoparkinsonism
    bradykinesia or akinesia, tremor, cogwheel rididity, postural/gait abnormality, onset 1 wk to 3 months, disappears in 48 hours, tx with ACh (1st line), amantadine, can also use these prophylactically
  21. tardive dyskinesia
    late abnormal movement, extremely rare with SGAs, more common with FGAs, worse with stress and disappear with sleep, 6mo-several years, can be irreversible if not caught early, tx usually minimally effective
  22. AIMS screening
    abnormal involuntary movements scale, necessary for ALL APs, baseline and every 3 mo
  23. treatment of neuroleptic malignant syndrome
    d/c AP and +- bromocriptine (dopa agonist) and +- dantrolene (muscle relaxant), can re-challenge after 2 weeks, SGA only
  24. lowest potency FGA
    chlorpromazine (Thorazine)
  25. high potency FGA
  26. clozapine-chart
    high ACh SE, dose-limiting SE, lots of sedation ++++, HOTN and Wt gain
  27. olanzapine-chart
    middle sedation, btwn clozapine and quetiapine, lots of wt gain, more robust action
  28. aripiprazole
    least sedating of SGAs but may not be better efficacy
  29. FGAs and EPS risk
    as potency increases, EPS increases
  30. FGAs and ACh SE
    as potency decreases, SEs increase
  31. Clozapine SE
    ACh, drooling, myocarditis(Black box warning), weight gain 60%, metabolic SEs, seizure risk 600-900 mg/d, agranulocytosis, hold if WBC <3000 or ANC<1500 until >3500 and >2000, d/c and do not rechallenge if WBC<2000 or ANC <1000, monitor weekly x 6 mo, then biweekly x 6mo, every 4 weeks thereafter
  32. risperidone optimal dose
    6mg, lower for 1st episode and early, above 6mg-higher risk of EPS equal to FGA, adjust in renal and hepatic impairment (max of 3 mg is suggested(, xr-Paliperidone ER (or Invega-brand) may not have much adv because risperdal is usually dosed qd hs anyways, may be good in liver dysfxn and may increase prolactemia, EPS significantly increased >9mg/d or an inx with carbamaz
  33. risperdal SE
    prolactin elevation, esp with increasing dose, akathesia, agitation, anxiety, insomnia EPS with 10mg/d is significantly>placebo
  34. olanzapine SE
    more efficacy vs. seroquel, faster onset and big kick, metabolic SE(hypergly and wt gain MORE than other SGAs), fluvoxamine increases olanza, more sedating good for aggression
  35. quetiapine-appropriate dose
    >=600mg to 900 mg used in clinical practice
  36. quetiapine SE
    sedation, lower risk of EPS (similr to clozapine), better with diabetes(wt gain, lipid and gluc abnorm lower than olanz and cloz), orthostatic hypotension, XR take on empty stomach, EPS=to placebo , no prolactin increase, seroquel=risperdal for met abnorm
  37. ziprasidone abs and SEs
    Geodon, 1/2 absorbed in fasted state, tk with food, EPS, weight neutral, QT prolongation but not significantly diff than other atypicals, quinolongest-QT prolongation and other drugs that cause arrythmias-amid, procain, thioridizaine, no CYP
  38. aripiprazole MOA
    partial ag of D2 and 5-HT1A; antagonist at 5-HT2A, dopamine and sero system stabilizer
  39. aripirazole SE
    weight neutral, sedation mild, EPS risk is moderate (lower than risperidone but still present), can be used for augmentation of depression, increased levels with fluoxetine
  40. asenapine, formulation and SEs
    Saphris, SL admin, somnolence, mod wt gain, EPS,hyperprolactinemia greater than placebo
  41. Iloperidone
    Fanapt, BID oral dosing, titrate over 4-7 days to reduce risk of orthostatic hypotension, prolactinemia, wt gain, lipid elevations and QT prolongation significantlly greater than placebo
  42. olanzapine contra in
    diabetics, greater metabolic
  43. Risperdal Consta
    IM inj q 2 weeks, continue oral AP for at least 3 weeks after 1st inj, then taper, depot is not active initially, 25 mg IM q 2 weeks, then titrate to 37.5 then 50 mg, dose adjustments no more freq than q 4 weeks
  44. Invega sustenna
    paliperidone palmitate, drug detectable in serum 1 day after injection, no need to continue PO formulation
  45. Zyprexa relprevv
    olanzapine pamoate, not to be confused with rapid acting IM formulation for tx of acute agitaiton, dosing based on previous PO olanzapine dose, PO supplementation not necessary after first dose, rare post-injection delirium/sedation syndrome, labeling requires pts to be observed in a healthcare setting for 3 hours after each inj
  46. haloperidol decanoate
    IM inj q 4 weeks, 15-20 times the previous oral dose initially then 10-15 times the previous oral dose, usually requires PO supplementation initially, pk conc in 6 days, ss in 3-4 months
  47. fluphenazine decanoate
    IM injections q 2-6 weeks, 12.5 mg flu dec. IM q 3 weeks=10mg flu PO daily, overlap of PO and IM needed
  48. Monitoring
    PANSS, SE(sedation, AIMS for involuntary movements/EPS, laboratory-extra(CBC and ANC for clozapine)
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neuro quiz 3-schizo
quiz 3