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SPP2 neuro/psych > schizophrenia/psychotic disorders > Flashcards

schizophrenia/psychotic disorders Flashcards

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1
Q

gene-environment interaction in developing schizophrenia

A

CMOT-marijuana

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2
Q

schizophrenia symptoms

A

positive: respond well to drug therapy; ex: hallucinations, delusions, bizarre behavior, thought disorders
negative: little response to drug therapy, newer agents are better; ex: blunted emotion, poor self care, social withdrawal, poverty in speech
cognitive: decrease in cognitive fxn, involves D1 receptors and glutamate receptors

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3
Q

receptors involved in schizophrenia

A

serotonin, dopamine, glutatamte

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4
Q

presynaptic agonists ___ NT concentration

A

decrease synthesis and release

cell tells itself that it’s releasing too much

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5
Q

presynaptic antagonists ___ NT conc

A

increase synthesis and release

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6
Q

dopamine antagonist use in schizophrenia

A

block presynaptic receptors - increase synthesis and release - also bock post synaptic receptors - dopamine cannot be used
dopamine originally increases, but basal levels change and the conc returns to normal

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7
Q

actions of D2 antagonists in CNS

A

basal ganglia: motor effects, extrapyramidal symptoms (EPS)
mesolimbic (best): therapeutic and decrease in cognition
mesocortical: hypofunction in schizophrenia, antagonists may exacerbate cognitive deficits
hypothalamus and endocrine systems: D2 receptor blockade in endocrine system
medulla: chemoreceptor trigger zone; D2 antagonists are anti-emetics

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8
Q

when we occupy __% of the dopamine receptors, we occupy __% of ___

A 
50;10
90;50
histamine receptors
sedation and weight gain
we need 70% occupancy to see therapeutic efficacy
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9
Q

EPS Sx and drug therapy

A

dystonia, pseudoparkinsonism, tremor, akathisia
benztropine, trihexyphenidyl, akineton - anticholenergic
diphenhydramine - antihistamine
amantadine - dopamine releasing agent

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10
Q

tardive dyskinesia

A

SE of antipsychotics
occur late, IRREVERSIBLE
Sxs: rhyhmic involuntary movements of the mouth, choreiform (irregular purposelessness), athetoid (worm-like), axial hyperkinesias (to and fro movements)
unkown MOA
monitor with AIMS q6mo
treatment: prevention, use least risky agent at lowest dose possibe and monitor (reduce dose, change to a different drug, eliminate anticholinergic drugs)

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11
Q

neuroleptic malignant syndrome (NMS)

A

serious and rapid; 10% fatality

symptoms: EPS symptoms with fever, impaired cognition
treatment: restore dopamine balance; d/c drug, DA agonists, diazepam or dantrolene

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12
Q

antipsychotic AEs

A

autonomic: loss of accomidation, dry mouth, difficulty urinating, constipation
CNS: parkinsons, akathisia, dystonia, tadrive dyskinesia, toxic confusional state, sedation
endocrine: amenorrhea-galactorrhea, infertility, impotence
other: weight gain

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13
Q

antipsychotic precautions and CIS

A

CV: increased QT prolongation
parkinsons
epilepsy (clozapine lowers seizure threshold)
diabetes (newer agents)

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14
Q

high D/5HT2a ratio leads to

A

EPS

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15
Q

aliphatic phenothiazines

A

1st generation antipsychotic
chlorpromazine, promezine, triflupromazine
used for H1 antagonist properties: promethazine, trimeprazine

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16
Q

piperidine phenothiazines

A

1st generation antipsychotic
mesoridazine, thioridazine (sedation, hypotension, anticholinergic, many SE)
fluphenazine, trifluoperazine, prochlorperazine, triethylperazine, perphenazine

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17
Q

thioxanthines

A

1st generation antipsychotic

thiothixene (modest EPS), chlorprothixene

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18
Q

butyrophenones

A

1st generation antipsychotic

haloperidol (EPS), droperidol (sedative), droperidol with fentayl

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19
Q

misc 1st generation antipsychotics

A

molindone - moderate EPS

pimozide

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20
Q

atypical/second generation antipsychotics

A

reduced EPS, efficacy for negative symptoms, similar or enhanced 5HT2A receptor antagonism vs D2
more metabolic problems - diabetes
affect multiple receptors, potency at D2 and 5HT2A, affinity at 2A is responsible for dec EPS

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21
Q

clozapine

A

atypical/second generation antipsychotics
most effective
2nd or 3rd line be it causes *agranolocytosis
SE: anticholinergic, antihistamine
decreased movement disorders, risk of diabetes

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22
Q

olanzapine

A

atypical/second generation antipsychotics

weight gain, less like to cause NV and movement disorders, risk of diabetes

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23
Q

loxapine

A

atypical/second generation antipsychotics
older agent
antidepressant

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24
Q

quetapine

A

atypical/second generation antipsychotics
antidepressant activity
low EPS, hypotension, sedation, risk of diabetes

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25
Q

risperidone

A

5HT2A and D2 antagonist
low EPS at 8 mg/day
weight gain/sedation

26
Q

ziprasidone

A

atypical/second generation antipsychotics

prolongs QT interval

27
Q

lurasidone

A

atypical/second generation antipsychotics
less weight gain and metabolic effects
fast onset
low doses similar effectiveness to high doses

28
Q

aripiprazole

A

atypical/second generation antipsychotics/ “third generation”
high affinity for 5HT2A and D2, D2 actions are dopamingeric-state dependent and/or it is functionally selective

29
Q

brexpiprazole

A

D2/D3 partial agonist
*less akathisia than aripiprazole
used for schizophrenia and as an adjunct to antidepressants for major depression

30
Q

cariprazine

A

**Once daily dosing (long t1/2 – 48 – 96 hours; active metabolite 1 – 3 weeks); moderate risk of weight gain; high risk of akathisia; high receptor binding affinity; P450 3A4 substrate (minimal 2D6, 20% renal elimination); not recommended in severe hepatic impairment or CrCl under 30 mL/min; max dose = 6 mg once daily – higher doses not more effective, but greater risk of akathisia. (brand only

31
Q

key features of psychotic disorders

A

delusions, hallucinations, disorganized thinking (speech), disorganized or abnormal motor behavior, negative symptoms

32
Q

most effective antipsychotic

A

clozapine - issue: granulocytosis

33
Q

consideration when choosing an antipsychotic

A

doses per day
side effects - tolerance, other disease states, risk factors?
previous drug therapy - success or failure? family members? what did they take?
cost of therapy - payer source? PO or IM?
concomitant therapy
monitoring - labs? weight? EKG?
smoker? more than 7 cigarettes/day will wipe out anything metabolized by 1A2

34
Q

Fluphenazine

A

injection: q2weeks, 10 mg PO = 12.5 mg IM, NO OVERLAP, oil-based (z-track)

35
Q

haloperidol

A

injection: q4weeks,
load: 20 times oral dose, maintenance: 10 times oral dose
oil-based, need to z-track

36
Q

Loxapine

A

Adasuve®
dosage form: capsule or Oral inhalation powder: 10mg/dose
dosing: Oral inhalation powder:
10mg dose per 24 hour
period
“Atypical Typical”
Adasuve® oral inhalation powder has a REMS – must be given in hospital setting with access to emergency services, contraindicated with history of lung disease; monitor closely for bronchospasm

37
Q

perphenazine

A

Increased use in recent years

due to CATIE study

38
Q

pimozide

A

3A4 substrate

QTc prolongation limits use; usual clinical use limited to Tourette’s disorder

39
Q

Thioridazine

A

**Significant QTc prolongation limits use; not generally initiated as new therapy; informed consent necessary

40
Q

Thiothixene

A

1A2 substrate

41
Q

aripiprazole

A

**Once daily dosing (long t1/2 – 72 – 96 hours); akathisia/anxiety side effects prominent; low risk of weight gain or metabolic syndrome; high receptor binding affinity; P450 2D6 and 3A4 substrate; LAIs (Abilify Maintena and Aristada) have dosing adjustments when using with strong 2D6 or 3A4 inhibitors or 3A4 inducers; LAI must have 2 (Abilify Maintena) or 3 (Aristada) week oral overlap

42
Q

asenapine

A

**Sublingual only; poor oral bioavailability; moderate weight gain; metabolic syndrome; QTc prolongation warning; P450 **1A2 substrate (brand only so expensive); nonadherence a problem due to metallic taste and unit-dose packaging that patients have trouble with; smoking decreases concentration; caffeine can increase; ? Efficacy for negative symptoms – some positive evidence

43
Q

brexpiprazole

A

**Once daily dosing (long t1/2 - ~ 91 hours with multiple doses), moderate risk of weight gain (more
than aripiprazole); akathisia (less than aripiprazole); high receptor binding affinity; P450 2D6 and 3A4
substrate – dosing adjustments with strong 2D6/3A4 inhibitors and 3A4 inducers; max dose reduction
to 3 mg daily (usual max 4 mg daily) with moderate to severe hepatic dysfunction or CrCl under 60
mL/min) (brand only – expensive)

44
Q

clozapine

A

**MOST EFFECTIVE; significant side effects requiring slow dose titration – agranulocytosis
(required REMS monitoring), *cardiomyopathy, hypersalivation, hypotension, metabolic syndrome,
*dose-related seizures; QTc prolongation, constipation, sedation; P450 1A2 substrate (3A4 minor);
REMS – must monitor ANC weekly x 6 months, biweekly x 6 months, then every 4 weeks

45
Q

iloperidone

A

**Boxed warning for QTc prolongation; orthostatic hypotension requiring slow dose titration with necessary twice daily dosing; moderate weight gain; metabolic syndrome; P450 2D6 and 3A4 substrate; (brand only – expensive)

46
Q

lurasidone

A

**Once daily dosing (t1/2 – 18 hours); MUST take with food (meal) to improve bioavailability; prominent akathisia; low risk of weight gain/metabolic syndrome; P450 3A4 substrate; Usual max dose = 160 mg; moderate hepatic impairment or CrCl under 50 mL/min – max dose = 80 mg; severe hepatic impairment – max dose = 40 mg

47
Q

olanzapine

A

**Once or twice daily dosing; if daily, give at bedtime (high risk of sedation); significant weight gain,
hyperglycemia, hyperlipidemia, metabolic syndrome risk; anticholinergic at higher doses (> 15
mg/day); P450 1A2 substrate; LAI – Zyprexa Relprevv – REMS requiring patient consent to
treatment and monitoring after dose

48
Q

paliperidone

A

**9-OH metabolite of risperidone; once daily dosing (t1/2 - 23 hours); ER dosage form – ghost tablet; renal elimination – dose adjustment in renal impairment; higher risk of EPS and hyperprolactinemia;
moderate weight gain/metabolic syndrome; QTc prolongation warning; LAIs – Invega Sustenna – given IM every 4 weeks; Invega Trinza – given IM every 12 weeks

49
Q

quetiapine

A

**Broad dose range (300 – 800 mg daily); short t1/2 but still give once daily if possible; significant sedation; **QTc prolongation boxed warning; moderate risk of weight gain/metabolic syndrome; P450 **3A4 substrate; abuse potential – used to “come down” from stimulants/cocaine; can be abused for its own effects – similar to benzodiazepines; (XR dosage form - brand)

50
Q

risperidone

A

**Often seen as first-line treatment; once daily dosing usual; **higher risk of EPS and hyperprolactinemia; moderate risk of weight gain/metabolic syndrome; P450 **2D6 substrate (produces paliperidone); LAI – Risperdal Consta – given 25 mg IM every 2 weeks; must supplement with oral risperidone/antipsychotic for first few weeks

51
Q

ziprasidone

A

**Twice daily (but can be given once daily); MUST be taken with food (meal) to improve
bioavailability; *lower risk of weight gain/metabolic syndrome; low risk of akathisia; no significant
P450 metabolism; QTc prolongation warning; *DRESS warning from post-marketing surveillance

52
Q

invega sustenna

A

234mg loading dose on day 1; 156mg booster on day 8; 117mg 5 weeks after loading dose (then every 4 weeks); this strategy followed = no oral overlap required

53
Q

zyprexa relprevv injection

A

side effects similar to oral olanzapine
**PDSS (post-dose delirium sedation syndrome): significant sedation, patient may not pick up dose; patient must stay in clinic and have side effect monitoring for 3 hours; must have accompanied ride home
May required oral overlap indefinitely

54
Q

immediate release antipsychotics

A

haloperidol*, chlorpromazine, fluphenazide all w lorazepam
ziprasidone, aripiprazole can be given with lorazepam
olanzipine CANNOT be given with lorazepam

55
Q

EPS etiology and treatments

A

acute dystonia: young, black, male, treat w IM anticholinergic NOW (benztropine, diphenhydramine)
drug-induced parkinsons: oral anticholinergic (benztopine, diphenhydramine, trihexyphenidyl), amandatine
akathisia: restlessness, inc suicidal thoughts/behaviors, betablocker (**propranolol 20 mg BID), benzodiazepine (lorazepam), oral anticholinergic, lower dose of antipsychotic
tardive dyskinesia - lower dose of antipsychotic or switch

56
Q

neuroleptic malignant syndrome

A

Life-threatening = medical emergency
Caused by effects of antipsychotics on dopamine blockade
Hyperpyrexia, tachycardia, labile blood pressure
Treatment: supportive, discontinue antipsychotics, consider dopamine agonists

57
Q

metabolic adverse effects

A

hyperglycemia, hyperlipidemia, hypertension, weight gain
Most: clozapine and olanzapine
Moderate: quetiapine, risperidone, paliperidone, asenapine, iloperidone
Low to No Risk: ziprasidone, lurasidone, aripiprazole
Must monitor: weight, waist circumference, **fasting blood glucose, A1C, fasting lipids

58
Q

metabolic monitoring

A

personal/family hx - baseline and yearly
weight - baseline, q4 weeks, q 3 mo
waist circumference - baseline and yearly
BP - baseline, 12 weeks, yearly
FPG/A1c - baseline, 12 weeks, yearly
fasting lipids - baseline, 12 weeks, every 5 years

59
Q

disease course

A

*men: late teens, early 20s
*women: late 20s, early 30s
aging patients: less psychosis, more negative and cognitive Sxs

60
Q

“typical” antipsychotic pearls

A

Haloperidol used most often- PRN and maintenance
More EPS with higher potency typical
Often used after failure of aytpicals

61
Q

polypharmacy

A

Must have failed 2 courses of monotherapy and clozapine (unless reason not to take it) before polypharmacy
Common in clinical practice, some patients may require it

62
Q

other drug related info

A
  • *Aripiprazole: FDA-approved for major depressive disorder in combination with anti-depressant
  • *Clozapine: WBC/ANC must be monitored weekly x 6 weeks, every 2 weeks x 6 weeks, then every 4 weeks to maintain ANC >2000
  • *Quetiapine: recent boxed warning for QTc prolongation

SPP2 neuro/psych (5 decks)

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