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Psychopharmacology > Lecture 18: Antipsychotics > Flashcards

Lecture 18: Antipsychotics Flashcards

1
Q

factors behind variance in drug effectiveness (8)

A
  1. liver/GI function
  2. compliance
  3. other drugs
  4. genetics
  5. epigenetics
  6. age
  7. diet
  8. comorbidity
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2
Q

3 positive symptoms of schizophrenia

A

delusions
hallucinations
thought disorders

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3
Q

3 negative symptoms of schiophrenia

A

anhedonia
withdrawal
blunting of emotional expression

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4
Q

3 phases of schizo

A
  1. premorbid
  2. prodromal
  3. full syndrome
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5
Q

premorbid

A

subtle motor, cognitive, or social impairments

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6
Q

prodromal

A

mood symptoms, cog symptoms, social withdrawal, obsessive behaviors

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7
Q

full syndrome

A

substantial functional deterioration in self care, work, and relationships

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8
Q

SP was recently recognized as a ___ disease

A

neurodevelopmental

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9
Q

neurodevelopmental disease

A

significant abnormalities in brain structure and function; highly heritable; misconnection syndrome

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10
Q

diagnostic criteria for schizophrenia (3)

A

for at least 6 months:

  1. prominent psychotic symptoms for at least 1 wk
  2. poor psychosocial function
  3. only brief mood disturbance
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11
Q

onset of SP

A

late adolescence

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12
Q

prevalence of SP

A

1%

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13
Q

lethality of SP

A

10-15% suicide rate

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14
Q

3 theories of NT systems underlying SP

A
  1. DA hypothesis (D2 receptors)
  2. 5HT (5HT2A)
  3. glutamate-NMDAR (NMDAR)
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15
Q

summary of DA theory

A

develops from dysreg of DA brain pathways, resulting in overactivity of DA function

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16
Q

5 pieces of ev for DA theory

A
  1. stimulant drug abuse
  2. APs are DA antagonists
  3. APs have affinity for D2
  4. affinity for D2 is best predictor of dose
  5. psychosis in parkinson’s patients treated with increased DA
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17
Q

why can’t you use a drug with the highest possible D2 affinity?

A

need DA in basal ganglia for normal movement

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18
Q

essential culprit in parkinson’s disease

A

loss of DA neurons in basal ganglia

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19
Q

5 symptoms of parkinson’s

A
  1. bradykinesia
  2. akinesia
  3. altered gait
  4. cogwheel rigidity
  5. micrographia
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20
Q

treatment of PD can cause ___

A

hallucinations

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21
Q

major concern is that APs can cause ___

A

tardive dyskinesia

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22
Q

tardive dyskinesia (6)

A

involuntary, repetitive, purposeless body movements

  1. grimacing
  2. lip pursing
  3. tongue movement
  4. blinking
  5. lip smacking
  6. lip puckering
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23
Q

summary of 5HT theory

A

LSD exerts effects on 5HT2a, so thought that 5HT2 antagonism might be responsible for beneficial effects of neuroleptics

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24
Q

neuroleptic

A

APs, major tranquilizers

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25
Q

believed that serotonin does or does not play a role in SP?

A

does not

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26
Q

5HT2 receptor antagonism plays a role in ___ of newer APs

A

improved neurological side effect profile

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27
Q

glu-NMDAR theory

A

NMDAR hypofunction may be involved; ketamine and PCP have SP-like symptoms

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28
Q

chlorpromazine: brand name type, class

A

thorazine; phenothiazine; 1st gen

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29
Q

chlorpromazine effects (4)

A

reduces amount of anesthetic needed for surgery

  1. sedation
  2. calmness
  3. lack of interest in and detachment from external stimuli
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30
Q

MoA of chlorpromazine

A

DA antagonist

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31
Q

neuroleptic state

A

state of apathy, lack of initiative, and limited range of emotion

32
Q

haloperidol: class, type, and brand name

A

first gen
butyrophenones
haldol

33
Q

2 important 1st gen APs

A

chlorpromazine (thorazine)

haloperidol (haldol)

34
Q

clozapine generation

A

2nd gen

35
Q

clozapine was effect for __% of patients who didn’t respond to standard treatments

A

30%

36
Q

clozapine produced little or no symptoms of ___

A

movement disorders

37
Q

serious side effect of clozapine

A

toxic effect on WBCs

38
Q

3 important 2nd gen APs

A
  1. risperidone (risperidal)
  2. olanzapine (zyprexa)
  3. aripiprazole (abilify)
39
Q

third gen AP

A

abilify

40
Q

did clozapine work better or worse than FGAs?

A

better

41
Q

which SGAs worked better than FGAs?

A
  1. clozapine
  2. olanzapine
  3. risperidone
42
Q

american study on AP effectiveness

A

CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness)

43
Q

CATIE findings on olanzapine

A

more weight gain/metabolic effects

44
Q

CATIE findings on clozapine

A

clozapine more effective than other atypical APs

45
Q

3 findings of CUtLASS

A
  1. SPs did just as well on APs from either category
  2. patients taking FGAs showed trend toward greater improvement on quality of life and symptom scores
  3. patients had no clear preference
46
Q

weakness of CUtLASS

A

excluded clozapine

47
Q

3 conclusions of CATIE and CUtLASS

A
  1. no clear clinical adv of 2nd gen or 1st gen for SP
  2. 2nd gen advantages in relapse prevention, reduced EPS, and use for bipolar depression
  3. SGAs are expensive, cause weight gain, and metabolic problems
48
Q

2 differences between SGAs and FGAs

A

SGAs have lower affinity for D2 and higher affinity for 5HT

49
Q

advantage of lower affinity for D2 and higher for 5HT

A

separation btwn antipsychotic efficacy and induction of movement disorders

50
Q

why does the separation of AP effects and movement disorders exist in 2nd gen?

A
  1. 5HT inhibits DA release in nigrostriatal pathway, but not mesolimbiccortical
    SGAs selectively enhance DA release in striatum, mitigates EPS
    endogenous 5HT blocks DA release in striatum, but not limbic sys and neocortex; 5HT antag pref increases DA in striatum
  2. lower affinity for D2 means easier displacement from receptor by mass action; DA conc higher in striatum than limbic system and frontal cortex
51
Q

1st gen APs necessarily cause ___

A

parkinsonian side fx

52
Q

are FGAs lipid soluble?

A

yes

53
Q

half life of FGAs

A

20-40 hrs

54
Q

how long are metabolites detectable for FGAs?

A

months

55
Q

do FGAs have large or small distribution volume?

A

large

56
Q

FGAs block what 4 receptor types?

A
  1. D2
  2. ACh (muscarinic)
  3. histamine
  4. NE
57
Q

what is responsible for FGA motor disturbances?

A

blocking DA receptors in basal ganglia

58
Q

dystonia

A

involuntary muscle contractions and sustained, abnormal, bizarre postures of limbs, trunk, head, and tongue

59
Q

5 side effects and toxicity for FGAs

A
  1. sedation
  2. posutal hypotension (lowered blood pressure from standing up)
  3. lowered seizure threshold
  4. photosensitivity
  5. anticholinergic side fx
60
Q

4 anticholinergic side fx

A
  1. constipation
  2. dry mouth
  3. blurry vision
  4. memory problems
61
Q

thorazine cholinergic blockade causes what 7 symptoms?

A
  1. dry mouth
  2. pupil dilation
  3. blurred vision
  4. cog impairments
  5. constipation
  6. urinary retention
  7. tachycardia
62
Q

2 symptoms of noradrenergic antagonism

A
  1. hypotension

2. sedation

63
Q

3 symptoms of histaminergic blockade

A
  1. sedation
  2. antiemetic effects
  3. weight gain
64
Q

side effect of serotonin blockade

A

weight gain

65
Q

what AP causes the most weight gain? 2nd most?

A

clozapine; olanzapine

66
Q

why does clozapine have fewer EPS than FGAs?

A

reduced D2 receptor affinity

67
Q

5 serious side fx of clozapine

A
  1. sedation
  2. extreme weight gain (10 lbs in 10 weeks)
  3. sialorrhea (increased saliva)
  4. agranulosis (WBC decrease)
  5. lowered seizure threshold
68
Q

4 symptoms of metabolic syndrome

A
  1. weight gain
  2. diabetes
  3. elevated lipids
  4. cardiac abnormalities (torsades de pointes)
69
Q

abilify is a partial agonist at (3)

A
  1. D2
  2. 5HT1a
  3. 5HT2
70
Q

how is abilify a stabilizer?

A

when DA levels are low, it produces an agonist action, but when DA levels are high, it competes but has less effect (lower affinity than endogenous DA)

71
Q

what is responsible anxiolytic/antidepressant effects of abilify?

A

5HT1a agonism

72
Q

which newer antipsychotic is not approved for bipolar?

A

clozapine

73
Q

5HT antagonism removes ___

A

endogenous 5HT inhibition of DA release in striatum

74
Q

important phenothiazine

A

chlorpromazine

75
Q

important butyrophenone

A

haloperidol

Psychopharmacology (22 decks)

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