neuro quiz 3-schizo

extrapyramidal system, movement

movement disorders

extra dopa can inc pos sx, arousal, memory, stimulus, processsing, motivational behavior

relief of psychosis (pos sx)

cognition, communication, social fxn, response to stress

relief of psychosis, akathesia? worsening of neg symptoms

regulates prolactin release

increased prolactin concentration

60-65%, >77%

alpha1, H1 and cholinergic

haloperidol, fluphenazine, higher D2 receptor binding affinity, greater potentialfor causing EPS side effects and prolactin elevation

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

5-HT blockade, reverses in mesocortical, nigrostriatal and tuberoinfundibular pathways

thioridazine=highest risk, SGAs thought to have lower risk than FGAs but recent studies have shown similar with SGAs

• FGA: low potency agents > than high potency
• SGA: varies

prolactin elevation, gynecomastia, galactorrhea, sexual dysfxn, amenorrhea, SGAs have LOWER risk than FGAs

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)

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

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

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

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

abnormal involuntary movements scale, necessary for ALL APs, baseline and every 3 mo

d/c AP and +- bromocriptine (dopa agonist) and +- dantrolene (muscle relaxant), can re-challenge after 2 weeks, SGA only

chlorpromazine (Thorazine)

haloperidol

high ACh SE, dose-limiting SE, lots of sedation ++++, HOTN and Wt gain

middle sedation, btwn clozapine and quetiapine, lots of wt gain, more robust action

least sedating of SGAs but may not be better efficacy

as potency increases, EPS increases

as potency decreases, SEs increase

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

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

prolactin elevation, esp with increasing dose, akathesia, agitation, anxiety, insomnia EPS with 10mg/d is significantly>placebo

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

>=600mg to 900 mg used in clinical practice

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

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

partial ag of D2 and 5-HT1A; antagonist at 5-HT2A, dopamine and sero system stabilizer

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

Saphris, SL admin, somnolence, mod wt gain, EPS,hyperprolactinemia greater than placebo

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

diabetics, greater metabolic

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

paliperidone palmitate, drug detectable in serum 1 day after injection, no need to continue PO formulation

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

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

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

PANSS, SE(sedation, AIMS for involuntary movements/EPS, laboratory-extra(CBC and ANC for clozapine)