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psychopharm > psychotic disorders > Flashcards

psychotic disorders Flashcards

1
Q

dopamine in schizophrenia

A

mesolimbic: elevated dopamine–> positive symptoms (antipsychotics work on this system)
prefrontal cortex (mesocortical): inadequate dopaminergic activity–> negative symptoms
treating with antipsychs blocks dopamine:
–>hyperprolactinemia in tuberoinfundibular pathways
–>EPS in nigrostriatal pathways

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2
Q

other NTs in schizophrenia

A

elevated serotonin
elevated NE
decreased GABA
decreased glutamate (NMDA) receptors (ketamine (NMDA antagonist) causes psychotic symptoms)

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3
Q

the best antipsychotic

A

clozapine (clozaril)- 30% of poor responders will respond to clozapine
start with 25-50 mg, Titrate gradually to reduced maintenance range of 100 to 150 mg/day; maximum 300 mg/day (true max 900mg)
-less likely to cause TD

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4
Q

newer antipsychotic better at treating negative symptoms compared to risperidone (2017)

A

cariprazine (vraylar)

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5
Q

1st generation antipsychs with typical starting dose/dose range daily/max

A

chlorpromazine (thorazine)- 25-200mg/400-600 mg/800 mg
fluphenazine (prolixin)- 2-15 mg/12 mg
haloperidol (haldol) 2-20 mg/30 mg (FDA 100mg)
loxapine (adasuve)- 20-80 mg/100 mg
perphenazine (trilafon)- 8-16mg/12-24 mg/24 mg
pimozide (orap)- 1-2mg/8-10 mg/10 mg
thioridazine (mellaril)- 150mg/200-600 mg/600 mg
thiothixene (navane)- 5-10mg/10-20 mg / 30 mg
trifluroperazine (stelazine)-4-10mg/15-20 mg/40 mg

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6
Q

2nd generation antipsychs with typical starting dose/dose range/max

A

aripiprazole (abilify)- 10-15 mg/30 mg
asenapine (saphris)- 10-20mg/20mg
brexpiprazole (rexulti)- 0.5-1mg/2-4mg/4mg
cariprazine (vraylar)- 1.5-6mg/6mg
clozapine (clozaril)- 25-50mg/150-600mg/900mg
iloperidone (fanapt)- 2mg/12-24mg/24mg
lurasidone (latuda)- 40-80mg/160mg
olanzapine (zyprexa)- 5-10mg/10-20mg/30mg
paliperidone (invega)- 6-12mg/12mg
pimavanserin (nuplazid)- 34mg/34mg
quetiapine (seroquel)- 50mg/150-750mg/750mg (IR), 400-800mg/800mg (ER)
risperidone (risperdal)-1-2mg/2-6mg/8mg
ziprasidone (geodon)-40-80mg/40-160mg/200mg

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7
Q

Resolution of psychotic symptoms with medication generally occurs over ?

A

several days and may take as long as 4-6 mg weeks
(most patients who will improve on an antipsychotic show the most rapid improvement in the first 2 weeks) *PORT trial 2-6wks
The dose of most antipsychotics should be titrated from an initial dose to the therapeutic range as quickly as tolerated EXCEPT
quetiapine, clozapine, and iloperidone need to be increased gradually before reaching a therapeutic dose

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8
Q

initial negative SEs to antipsychs

A

sedation, restlessness, or postural hypotension

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9
Q

Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) showed?

A

patients who gained weight during the first phase of antipsychotic treatment frequently lost weight when they were changed to ziprasidone (geodon)

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10
Q

toleration of antipsych discontinuation

A

generally well tolerated, except for clozapine, for which both cholinergic rebound and withdrawal-emergent movement disorders have been reported A slow taper of clozapine over one to two weeks is recommended. Chlorpromazine and thioridazine can also cause cholinergic rebound and should be reduced over a week or more

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11
Q

treatment-resistant schizophrenia

A

respond inadequately to an initial antipsychotic, dose adjustments, or a change in antipsychotics

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12
Q

antipsych for persistant suicidality

A

clozapine

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13
Q

EPS/akathisia treatment

A

benzos; eg, lorazepam (ativan) can be started at 0.5 mg orally twice daily and incrementally increased to a maximum of 6 to 10 mg/day
anticholinergics (benztropine (cogentin), diphenhydramine), B-blockers, amantadine (symmetrel)
-5% risk of developing TD per year treated with antipsych

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14
Q

Up to half of individuals with schizophrenia have a comorbid ?

A

substance use disorder

Use of stimulants such as PCP, meth, and cocaine can cause agitation, as can withdrawal from alcohol or benzos

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15
Q

B52

A

A combination of haloperidol 5 mg, lorazepam 2 mg, and benztropine 1 mg given intramuscularly can be effective to treat severe agitation in schizophrenia

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16
Q

sedating antipsychotics for agitated patients

A

Risperidone 1 to 2 mg or olanzapine 5 to 10 mg

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17
Q

Oral rapidly dissolving formulations are available for

A

risperidone, olanzapine, asenapine, and aripiprazole

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18
Q

receptors blocked by 1st generation antipsychotics

A

Dopamine D2

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19
Q

receptors blocked by 2nd generation antipsychotics

A

Dopamine D4 > D2, Serotonin 5-HT2A

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20
Q

The Schizophrenia Patient Outcomes Research Team (PORT) recommended NOT treating first episodes with ?

A

clozapine or olanzapine

both of these medications are associated with more weight gain, insulin resistance and dyslipidemia

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21
Q

younger patients and first episode patients have a greater vulnerability to side effects such as

A

weight gain and EPS

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22
Q

The Schizophrenia PORT recommended that first-episode patients receive lower antipsychotic doses

A

in the lower half of the recommended dose range
i.e. 1-3 mg of risperidone or 10 mg of aripiprazole daily
EXCEPT quetiapine, which may require titration to 500-600 mg daily

23
Q

For patients with schizophrenia who have recovered from an acute psychotic episode, we (Schizophrenia PORT) suggest that antipsychotic medication should be continued ?

A

indefinitely, even for patients who have achieved remission from a first psychotic episode

24
Q

Results of seven-year follow-up assessment of patients randomly assigned to either a dose reduction strategy or to maintenance antipsychotic treatment

A

dose reduction strategy had a higher rate of relapse in 2 years
BUT dose reduction strategy experienced a higher rate of recovery at 7 years

25
Q

LAI (long-acting injectable) antipsychotics

A

Aripiprazole ER- Aripiprazole lauroxil (maintena)
Fluphenazine decanoate-1.25 mg every 3 weeks
Haloperidol decanoate
Olanzapine pamoate
Paliperidone palmitate- 4 wk (invega sustenna)
Paliperidone palmitate- 12 wk (invega sustenna)
Risperidone microspheres (consta)

26
Q

LAI antipsychotic indications

A
  • symptomatic with behaviors leading to highly adverse consequences (eg, arrests, assaults, self harm, loss of employment or housing).
  • medication nonadherence, possible the oral ingestion process did not build a high enough blood and subsequent brain drug level
  • dose dependent side effects (eg, EPS or sexual dysfunction), LAI may provide consistent blood level without higher daily peaks
27
Q

LAI contraindications

A

hypersensitivity to the meds, CNS depression, coma
Parkinson’s disease for haloperidol-LAI and subcortical brain damage, blood dyscrasias, and hepatic disease for fluphenazine-LAI

28
Q

initial dose of haloperidol-LAI

A

10 to 20 times the previous daily dose of oral haloperidol, given in four-week intervals, should not exceed 100 mg, if necessary break up into 2 doses (day 1 and day 3-7)

29
Q

post-injection delirium sedation syndrome (PDSS)

A

rare (less than one percent) but serious adverse even in patients receiving olanzapine-LAI
confusion, disorientation, anxiety, dizziness, excessive sedation, and EPS

30
Q

antipsychotics improving cognitive benefits?

other meds?

A

improve early on, less benefit in chronic schizophrenia
other meds: NMDA glutamatergic receptor agonists, glycine, D-serine, ampakine CX516, D-cycloserine, donepezil, rivastigmine, and galantine have failed to show significant benefit

31
Q

Patients treated with an antipsychotic for schizophrenia should be assessed prior to treatment if possible and at regular intervals for:

A
  • EPS, tardive dyskinesia
  • Symptoms of metabolic syndrome including measurements of BMI, waist circumference, HbA1c, serum lipids, and BP
  • ECG for patients with a history of cardiac disease or when starting an antipsychotic that prolongs the QT interval
32
Q

Changing to another antipsychotic

A

has been shown to be an effective strategy for addressing side effect problems but is not clearly associated with improved efficacy, with the exception of clozapine

33
Q

Adding a second antipsychotic medication

A

has not been proven efficacious in randomized trials. For patients with psychotic symptoms that do not respond to two trials of antipsychotic monotherapy, a trial of clozapine is strongly recommended before combining two antipsychotics

34
Q

low potency typical antipsychs risks and SEs

A 
chlorpromazine (thorazine)
thioridazine (mellaril)
-higher HAM SEs, less EPS/NMS
-more lethal in OD due to OTc prolongation, heart block, vtach
-higher seizure risks
35
Q

chlorpromazine

SEs

A

(thorazine)
SEs: orthostatic hypotension, skin discoloration, photosensitivity
can be used to treat N/V, intractable hiccups

36
Q

midpotency typical antipsychs

A

loxapine (loxitane)-metabolite is antidepressant, risk of seizure
thiothixene (navane)
molindone (moban)
perphenazine (rilafon

37
Q

highpotency typical antipsychs

A

haloperidol (haldol)
fluphenazine (prolixin)
trifluoperazine (stelazine) (approved for non psychotic anxiety)
pimozide (orap) (^risk QTc prolongation, vtach)
-higher affinity for dopamine receptors, lower dose needed
-less HAM SEs (sedation, hypotension, anticholinergic effects)
-greater risk EPS/TD

38
Q

anti-HAM SEs of antipsychotics

A

antihistaminic: sedation, weight gain
anti-a1 adrenergic: othrostatic hypotension, cardiac abnormalities, sexual dysfunction
antimuscarinic: dry mouth, tachycardia, urinary retention, blurry vision, constipation, narrow angle glaucoma

39
Q

NMS occurs most frequently in ?

A

young males early in treatment with high potency anti psychs (haldol)
-20% mortality if untreated

40
Q

NMS symptoms

A 
FALTERED
Fever
Autonomic instability (tachy, HTN
Leukocytosis
Tremor
Elevated CPK
Rigidity
Excessive sweating
Delirium (AMS)
41
Q

NMS treatment

A

stop med, supportive measures
may use dantrolene, bromocriptine, amantadine
-may restart med once resolved, yet higher risk for second episode

42
Q

other anti psych SEs

A

retinal pigmentation, lens/cornea deposits, rashes, photosensitivity
lowered seizure threshold
elevated LFTs, jaundice

43
Q

onset of antipsychotic SEs

A

NMS: anytime (typically early)
acute dystonia: hours-days
parkinsonism/akathisia: days-weeks
TD: months-years

44
Q

scale used to quantify and monitor for TD

A

AIMS

Abnomal Involuntary Movement Scale

45
Q

atypical antipsychotics are less likely to cause ?

also used for ?

A

EPS, TD, NMS

bipolar, acute mania, depression, borderline, PTSD, tic disorders

46
Q

clozapine SEs

A 
tachycardia, hypersalivation
most anticholinergic SEs
myocarditis
1% incidence agranulocytosis (stop if ANC drops below 1500/microliter)
4% incidence seizures
47
Q

Risperidone SEs

A

Risperdal, Consta (LAI)

^prolactin, orthostatic hypotension, reflex tachy

48
Q

Quetiapine SEs

A

Seroquel
sedation, orthostatic hypotension
less likely to cause EPS

49
Q

Olanzapine SEs

A

Zyprexa

weight gain, sedation

50
Q

Ziprasidone

A

Geodon
QTc prolongation
less likely to cause weight gain
TAKE WITH FOOD to promote absorption

51
Q

Aripiprazole

A

Abilify
partial D2 agonism
more activating (akathesia), less sedating
less potential for weight gain

52
Q

newer, expensive atypicals

A

paliperidone (Invega, Sustenna (LAI)
asenapine (Saphris)
iloperidone (Fanapt)
lurasidone (Latuda): take with food, used in Bipolar depression

53
Q

general atypical SEs

A

metabolic syndrome: weight gain, hyperlipidemia, hyperglycemia
anti-HAM
elevated LFTs
QTc prolongation

psychopharm (4 decks)

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