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Pmcol 200 > L13 > Flashcards

L13 Flashcards

1
Q

Psychotic disorders

A

Range of mental disorders that involve symptoms of psychosis

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2
Q

Psychosis

A

Loss of contact with reality

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3
Q

Effect of psychosis

A

Affects ability to think, feel, act

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4
Q

How is Schizophrenia diagnosed

A

Severe psychotic disorder

If person has 2+ symptoms for 6 months from core clusters: positive, negative, cognitive symptoms

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5
Q

Positive symptoms

A

mental phenomena that are absent in healthy individuals

e.g. hallucinations and delusions

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6
Q

Negative symptoms

A

loss or impairment of normal psychological function

e.g. loss of motivation and social withdrawal

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7
Q

Cognitive symptoms

A

poor concentration, disorganized thinking, poor memory,

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8
Q

the risk of schizophrenia is highly

influenced by

A

genes

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9
Q

_____ interact
with a wide range of ____ that can trigger
____ and ____ leading to schizophrenia

A 
predisposing genetic factors interact
with a wide range of environmental
factors that can trigger
neurochemical and structural
changes leading to schizophrenia
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10
Q

Schizophrenia is a _____ brain disease

A

Schizophrenia is a biochemical brain disease

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11
Q

Biochemicals =

A

Neurotransmitters

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12
Q

Biochemical Theories of

Schizophrenia

A
  1. Dopamine Hypothesis
  2. Glutamate Hypothesis
  3. Serotonin (5-HT) Hypothesis
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13
Q

Dopamine Hypothesis

A

Symptoms of schizophrenia are due to the

hyperactivity of the dopamine system

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14
Q

what drugs increase synaptic dopamine and what’s the effects

A

(amphetamine,
cocaine, cannabis)

delusions and hallucinations
at high doses

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15
Q

drugs that block dopamine receptors are

A

effective

antipsychotics (First Generation Antipsychotics)

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16
Q

Dopamine neurons are located in

A

few

discrete brain regions.

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17
Q

The largest population

of dopamine neurons are located in

A

the midbrain (ventral segmental area and substantial nigra).

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18
Q

Mesocortical/mesolimbic system:

A

dopamine
neurons located in the ventral tegmental area
project to the striatum and the prefrontal
cortex

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19
Q

Mesocortical/mesolimbic system mediates

A

mediate memory, learning, affect and

thought organization

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20
Q

hyperactivity in Mesocortical/mesolimbic system

A

psychotic symptoms

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21
Q

blocking dopamine transmission

A

effective at treating the positive symptoms

of schizophrenia

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22
Q

what type of protein receptors are dopamine receptors

A

gpcr

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23
Q

two

classes of dopamine receptors:

A

d1, d2

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24
Q

D1 receptors stimulate adenylate

cyclase via

A

Gs protein

subsequently activate cAMP-

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25
Q

relationship between D1 and antipsychotic drugs

A

a target for
antipsychotic drugs

unlikely to contribute to the therapeutic action of many anti-psychotics

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26
Q

what type of gpcr is D2; mechanism of action

A

Gi, inhibit the activity of adenylate cyclase

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27
Q

D2 and antipsychotic potency relationship

A

blocking D2 receptors is directly

related to clinical anti-psychotic potency

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28
Q

Nigrostriatal system

A

dopamine neurons in
the substantia nigra that project to the
striatum.

29
Q

Nigrostriatal system initiates

A

movement

30
Q

Nigrostriatal system inhibition

A

inhibiting this pathway is involved in the
production of tardive dyskinesias body) after long-term use of some
antipsychotics

31
Q

tardive dyskinesias

A

(involuntary movements of the face and

body)

32
Q

Tuberoinfundibular System

A

dopamine neurons in the arcuate nucleus that control hormone release in the pituitary

33
Q

how does dopamine release affect Tuberoinfundibular System

A

Dopamine released here inhibits the

secretion of prolactin and growth hormone

34
Q

long-term use of some anti-psychotics is

associated with

A

hyperprolactinemia

increased prolactin release

35
Q

Tuberoinfundibular System associated with (3)

A

amenorrhea, decreased

libido, and infertility

36
Q

Glutamate Hypothesis

A

Symptoms of schizophrenia
linked to deficiencies in glutamate signaling,
particularly in the cortex

37
Q

Glutamate Hypothesis support

A

effects of
phencyclidine (PCP/Angel dust) and ketamine
which are NMDA antagonists that produce
hallucinations and paranoid delusions

38
Q

current theory is that schizophrenia
associated with ___ ___ ___ on ___ ___ in the
___ ___.
(glutamate theory)

A

current theory is that schizophrenia associated with hypofunctional NMDA receptors on GABA interneurons in the cerebral cortex.

39
Q

hypofunctional NMDA

receptors leads to

A

overactivation of downstream glutamate

signaling to the ventral tegmental area

40
Q

Serotonin Hypothesis

A

Hypothesis: Symptoms of schizophrenia

due to increased serotonin signaling

41
Q

Serotonin Hypothesis inferential evidence

A

some 5HT agonists are hallucinogenic
(e.g. LSD)

5HT antagonist improves positive
symptoms of schizophrenia

42
Q

activation of 5HT-2A receptors in the ____ ____
cause ___ by ___
excitation of ____ _____
(activating the ____ _____ system)

A

activation of 5HT-2A receptors in the prefrontal cortex cause hallucinations by enhancing excitation of glutamate neurons (activating the mesolimbic dopamine
system)

43
Q

5HT-2A antagonists block __ release in the ___, thus reducing
hallucinations and other ___
symptoms

A

5HT-2A antagonists block glutamate
release in the cortex, thus reducing
hallucinations and other positive
symptoms

44
Q

First generation antipsychotics, aka

A

Typical Antipsychotics

45
Q

First generation antipsychotics target and efficacy

A

targets both classes of dopamine receptors (D1 and D2) efficacy particularly relates to D2 receptor antagonism

46
Q

example of first gen drugs

A

Haloperidol, chlorpromazine

47
Q

Second Generation Antipsychotics aka

A

Atypical Antipsychotics

48
Q

second gen targets

A

antagonists at both 5HT receptors and D2 receptors

49
Q

second gen affinity and result of affinity

A 
bind looser (lower affinity) to dopamine receptors
produce less dopamine related side effects
50
Q

second gen drugs

A

clozapine, risperidone

51
Q

Between ___-___% occupation of D2 receptors
is required to produce an antipsychotic effect
for both typical and atypical antipsychotics

A

60-80%

52
Q

what % of d2 r occupancy results in side effects and what are they

A

80%
Parkinson-like side effects (extra pyramidal symptoms),
elevated prolactin (hyperprolactinemia),
tardive dyskinesia

53
Q

kinetic hypothesis for mesolimbic/nigrostriatal pathway

___ is released into the synaptic cleft, where it binds to receptors on the ___ ____ membrane

A

dopamine is released into the synaptic cleft, where it binds to receptors on the post synaptic membrane

54
Q

binding efficiency of mesolimbic/nigrostriatal pathway and why

A

tight squeeze!

high degree of receptor rebinding

55
Q

kinetic hypothesis for Tuberoinfundibular pathway

A

dopamine secreted
into the blood stream and carried across the blood
brain barrier via the hypophysial portal system to the
pituitary gland

56
Q

binding efficiency of Tuberoinfundibular pathway and why

A

high degree of clearance, less receptor

rebinding

57
Q

Fast on, slow off compounds example

A

haloperidol

58
Q

fast on/slow off rate for compounds like haloperidol and side effects

A

high
receptor binding potential at D2 in the
striatum and pituitary

high extrapyramidal side effects
and increased prolactin release
(hyperprolactinemia)

59
Q

Fast on, fast off compounds eg

A

chlopromazine

60
Q

fast on/FAST OFF rate for compounds like chlopromazine and side effects

A

The fast on rate leads to high extrapyramidal symptoms

fast off rates results in prolactin release
staying normal

61
Q

Slow on, fast off compounds e.g.

A

clozapine

62
Q

slow on rates for compounds like clozapine

A

lower re-
binding potential and low
extrapyramidal symptoms

fast off rates result in prolactin release
staying normal

63
Q

clozapine has unique affinity for ___
receptors
side effect?

A

D4

agranulocytosis (loss of white blood
cells)

64
Q

Antipsychotic medications start to work within ___ or ___ (i.e. dopamine
receptor blockade reaches 65% quickly) but can take ____ to reach their
full effect

A

hours, days

4-6 weeks

65
Q

% of people resistant to schizophrenia treatment

A

30%

66
Q

% of people resistant to antipsychotic medication

A

50%

67
Q

effects of first gen antipsychotic meds

A

extrapyramidal symptoms, dyskinesias, prolactin release

68
Q

effects of second gen antipsychotic meds

A

cardiovascular effects, metabolic syndrome, diabetes,

weight gain

Pmcol 200 (12 decks)

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