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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
believed that serotonin does or does not play a role in SP?
does not
26
5HT2 receptor antagonism plays a role in ___ of newer APs
improved neurological side effect profile
27
glu-NMDAR theory
NMDAR hypofunction may be involved; ketamine and PCP have SP-like symptoms
28
chlorpromazine: brand name type, class
thorazine; phenothiazine; 1st gen
29
chlorpromazine effects (4)
reduces amount of anesthetic needed for surgery 1. sedation 2. calmness 3. lack of interest in and detachment from external stimuli
30
MoA of chlorpromazine
DA antagonist
31
neuroleptic state
state of apathy, lack of initiative, and limited range of emotion
32
haloperidol: class, type, and brand name
first gen butyrophenones haldol
33
2 important 1st gen APs
chlorpromazine (thorazine) | haloperidol (haldol)
34
clozapine generation
2nd gen
35
clozapine was effect for __% of patients who didn't respond to standard treatments
30%
36
clozapine produced little or no symptoms of ___
movement disorders
37
serious side effect of clozapine
toxic effect on WBCs
38
3 important 2nd gen APs
1. risperidone (risperidal) 2. olanzapine (zyprexa) 3. aripiprazole (abilify)
39
third gen AP
abilify
40
did clozapine work better or worse than FGAs?
better
41
which SGAs worked better than FGAs?
1. clozapine 2. olanzapine 3. risperidone
42
american study on AP effectiveness
CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness)
43
CATIE findings on olanzapine
more weight gain/metabolic effects
44
CATIE findings on clozapine
clozapine more effective than other atypical APs
45
3 findings of CUtLASS
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
weakness of CUtLASS
excluded clozapine
47
3 conclusions of CATIE and CUtLASS
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
2 differences between SGAs and FGAs
SGAs have lower affinity for D2 and higher affinity for 5HT
49
advantage of lower affinity for D2 and higher for 5HT
separation btwn antipsychotic efficacy and induction of movement disorders
50
why does the separation of AP effects and movement disorders exist in 2nd gen?
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
1st gen APs necessarily cause ___
parkinsonian side fx
52
are FGAs lipid soluble?
yes
53
half life of FGAs
20-40 hrs
54
how long are metabolites detectable for FGAs?
months
55
do FGAs have large or small distribution volume?
large
56
FGAs block what 4 receptor types?
1. D2 2. ACh (muscarinic) 3. histamine 4. NE
57
what is responsible for FGA motor disturbances?
blocking DA receptors in basal ganglia
58
dystonia
involuntary muscle contractions and sustained, abnormal, bizarre postures of limbs, trunk, head, and tongue
59
5 side effects and toxicity for FGAs
1. sedation 2. posutal hypotension (lowered blood pressure from standing up) 3. lowered seizure threshold 4. photosensitivity 5. anticholinergic side fx
60
4 anticholinergic side fx
1. constipation 2. dry mouth 3. blurry vision 4. memory problems
61
thorazine cholinergic blockade causes what 7 symptoms?
1. dry mouth 2. pupil dilation 3. blurred vision 4. cog impairments 5. constipation 6. urinary retention 7. tachycardia
62
2 symptoms of noradrenergic antagonism
1. hypotension | 2. sedation
63
3 symptoms of histaminergic blockade
1. sedation 2. antiemetic effects 3. weight gain
64
side effect of serotonin blockade
weight gain
65
what AP causes the most weight gain? 2nd most?
clozapine; olanzapine
66
why does clozapine have fewer EPS than FGAs?
reduced D2 receptor affinity
67
5 serious side fx of clozapine
1. sedation 2. extreme weight gain (10 lbs in 10 weeks) 3. sialorrhea (increased saliva) 4. agranulosis (WBC decrease) 5. lowered seizure threshold
68
4 symptoms of metabolic syndrome
1. weight gain 2. diabetes 3. elevated lipids 4. cardiac abnormalities (torsades de pointes)
69
abilify is a partial agonist at (3)
1. D2 3. 5HT1a 3. 5HT2
70
how is abilify a stabilizer?
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
what is responsible anxiolytic/antidepressant effects of abilify?
5HT1a agonism
72
which newer antipsychotic is not approved for bipolar?
clozapine
73
5HT antagonism removes ___
endogenous 5HT inhibition of DA release in striatum
74
important phenothiazine
chlorpromazine
75
important butyrophenone
haloperidol

Psychopharmacology (22 decks)

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