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.Pharmacology > Chapter 15: Schizophrenia and Bipolar Affective Disorder > Flashcards

Chapter 15: Schizophrenia and Bipolar Affective Disorder Flashcards

1
Q

what are the 2 categories of antipsychotics?

A

typical / 1st generation antipsychotics and atypical / second generation antipsychotics

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2
Q

mania or a manic episode is characterized by:

A

enhanced mood, increased activity, grandiosity (increased self-esteem), racing thoughts and decreased need for sleep

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3
Q

as mania persists, it may develop into ___ as the person loses sleep and mood may dip

A

psychosis

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4
Q

patients with bipolar affective disorder experience periods of ___ and periods of ___

A

mania and depression

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5
Q

what is psychosis?

A

altered state of mind with the inability to distinguish real from delusions or hallucinations and disorganized or paranoid thoughts may also be present

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6
Q

___ is the most common clinical presentation of psychosis?

A

schizophrenia

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7
Q

how does psychosis present in schizophrenia?

A

duration and severity may vary, but usually psychosis is not continuous and patients may have long periods w/o symptoms and lead normal lives

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8
Q

there is a strong ___ link in schizophrenia and most patients w/ the disease also have a ___ who has the disease

A

genetic; relative

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9
Q

schizophrenia occurs in ~__% of the population

A

1

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10
Q

___ psychosis can occur in response to severe illness or drug use

A

acute

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11
Q

___ drugs are used to treat conditions where psychosis occurs

A

antipsychotic

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12
Q

the 2 important NT involved in schizophrenia are __ and __

A

DA and 5-HT

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13
Q

the DA hypothesis of schizophrenia proposes:

A

excess DA in certain brain regions causes the development of positive symptoms of schizophrenia

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14
Q

the serotonin hypothesis of schizophrenia proposes:

A

positive and negative symptoms of schizophrenia is caused by increased signalling by the 5-HT receptors which modulate levels of DA in many brain regions

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15
Q

the glutamate hypothesis of schizophrenia proposes:

A

modified glutamate signalling contributes to dystregualtion of neuronal circuits

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16
Q

what is the general consensus around the hypotheses of schizophrenia?

A

that serotonin and DA are imbalanced (not linked significantly to glutamate)

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17
Q

what are 2 important pathways to consider the roles of 5-HT and DA in schizophrenia?

A
  1. mesolimbic

2. mesocortical

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18
Q

in schizophrenia, in the mesocortical pathway, ___DA is released, causing the symptoms of: ______ (which are the ____(+/-) symptoms of schizophrenia

A

less; apathy, social withdrawal, reduced interest and motivation. Negative symptoms

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19
Q

in schizophrenia, in the mesolimbic pathway, ___DA is released into the nucleus accumbens and activates ___ receptors. This causes the ____(+/-) symptoms of schizophrenia

A

increases; D2; +

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20
Q

what are the + symptoms of schizophrenia that are caused by excess DA release into the nuclei accumbens?

A

delusions and hallucinations

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21
Q

in the mesolimbic pathway, excess DA is released into the ___ (brain region)

A

nucleus accumbens

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22
Q

the mesocortical pathways can ___(directly/indirectly) influence mesolimbic pathways

A

indirectly

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23
Q

reduced DA input into mesocortical neurons can result in ___ of the mesolimbic circuits

A

disinhibition

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24
Q

what brain region is commonly associated with the positive symptoms of schizophrenia?

A

nucleus accumbens

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25
Q

the ____ is the site of dopaminergic synapses from the mesolimbic pathway

A

nucleus accumbens

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26
Q

what DA type receptor is highly found in the nucleus accumbens?

A

D2

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27
Q

blocking ___receptors is the primary MOA of typical antipsychotics

A

D2

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28
Q

D2 receptors are expressed in brain regions other than the nucleus accumbens, what is the issue with this interns of antipsychotic use?

A

attempted to lower DA signalling in the mesolimbic pathway may also affect other pathways

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29
Q

the nigrostriatal pathway goes from the ___ to the ___

A

substance nigra to the striatum

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30
Q

antipsychotics acting on the D2 receptors along the nigrostriatal pathway leads to what types of ADR?

A

Parkinson’s-like movements

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31
Q

the tuberoinfundibulnar pathway goes from the ___ to the ___

A

hypothalamus to pituitary

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32
Q

the tuberinfundibular pathway is involved in regulation of ___hormones

A

endocrine

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33
Q

blocking D2 receptors in the pituitary can lead to increase in ___hormone which can cause ____effects

A

prolactin; low libido, infertility, enlargement of breast tissue

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34
Q

most ___ antipsychotics also act in the striatum, causing Parkinson’s like effects, often called ___ symptoms

A

typical; extrapyramidal

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35
Q

the ADR of typical antipsychotics are often results in ___to medication regimens

A

poor adherence

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36
Q

the first antipsychotic to be used clinically was ___ in the 1950’s

A

chlorpromazine

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37
Q

chlorpromazine has significant ____effects when administered to agitated patients, which lead to its wide-spread institutional use in the ‘50’s and ‘60’s

A

calming

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38
Q

chlorpromazine was the first ___ antipsychotic agent in use

A

typical

39
Q

what happened that made the DA theory of schizophrenia really take off?

A

it was found that chlorpromazine blocked DA receptor s

40
Q

the ability of an agent to block ___receptor and produce ___effecst are the primary characteristic of a typical antipsychotic

A

DA; psychosis

41
Q

the primary action of typical antipsychotics is to block ___

A

DA recepts

42
Q

how does blocking the DA receptors in the nucleus accumbens help schizophrenia?

A

reduces DA signalling, which alleviates hallucinations and delusions

43
Q

Haloperidol is an example of a ___ type drug

A

typical antipsychotic

44
Q

Haloperidol is typically used bc of its ability in ___ (what is the formulation?)

A

long-acting depot formulation (IM injections)

45
Q

why is an IM injection of Haloperidol beneficial?

A

makes admin easier for patients who forget or are non-aderhent with medications

46
Q

which has a higher potency as a D2 receptor antagonist, Haloperidol or chlorpromazine?

A

Haloperidol

47
Q

how often is an IM injection of Haloperidol given?

A

monthly

48
Q

typical antipsychotics are unique in that their clinical potency is directly proportional to their ____

A

binding affinity at the D2 receptor

49
Q

the potency of an antipsychotic used to treat schizophrenia is measured by its ability to __

A

resolve the positive symptoms of schizophrenia

50
Q

the potency is measured by what phamacokinetics term?

A

ED50

51
Q

affinity is measured by what pharmacokinetics term?

A

K

52
Q

on a graph of D2 R affinity vs Potency, chlorpromazine and haloperidol both land very close to the line on the graph, meaning ___

A

their potency is directly related to their binding affinity

53
Q

in typical antipsychotics, drugs with a higher D2 receptor affinity will have a ____potency

A

higher (lower ED50)

54
Q

do atypical agents such as clozapine follow the same affinity/potency relationship as typical antipsychotics?

A

no

55
Q

Clozapine’s (an atypical antipsychotic) potency is much higher than would be expected based on its affinity for the D2 receptor, what does this mean in terms of hypotheses for schizophrenia?

A

it means dopamine is not the only contributor

56
Q

the serotonin hypothesis if schizophrenia suggests that blocking ___ receptors will increase ___ release in the cortex which is beneficial for the negative symptoms of schizophrenia a

A

5-HT; DA

57
Q

the serotonin hypothesis involves blocking 5HT receptors in what part of the brain?

A

mesocortical pathway

58
Q

atypical antipsychotics have more activity at ___ receptor that __ receptors

A

5HT; DA

59
Q

t/f the atypical antipsychotics do still have some D2 blocking which helps alleviate the positive symptoms of schizophrenia

A

t

60
Q

atypical antipsychotics restore ___ inputs into the mesolimbic pathway

A

inhibitory

61
Q

clozapine and Olanzapine are examples of ____antipsychotics that block both __ and ___ receptors

A

atypical; 5HT and DA

62
Q

the use of the clozapine and olanzapine results in management of both ___ and ___

A

+ and - symptoms of schizophrenia

63
Q

MOA of Aripiprazole

A

atypical antipsychotic which is a 5HT antagonist and D2 partial agonist

64
Q

t/f partial agonists produce some agonist activity, but to a lesser extent

A

t

65
Q

what is the benefit of Aripiprazole being a partial agonist of D2?

A

when the partial agonist binds, the full agonist (DA) cannot bind, so competitive antagonism happens, but some physiologic effect is maintained, This reduces the effects that lead to Parkinson’s like ADR

66
Q

many ADR common to most antipsychotics are related to ___

A

blocking D2 in unintended regions of the brain

67
Q

one of the most common and most treatment-limiting effects of antipsychotics is ____ effects that occur when D2 is blocked in the striatum

A

extrapyramidal (EPS) which cause Parkinson-like effects

68
Q

antipsychotics that have lower ____ to the d2 receptor cause fewer EPS effects and may be better tolerated

A

affinity

69
Q

what branch of antipsychotics has reduced affinity for D2 receptors?

A

atypical

70
Q

aside from EPS effects, what are some ADR associated with activating off-target D2 receptor?

A

sedations, restlessness, elevated prolactin which can lead to sexual dysfunction and infertility

71
Q

off-target effects of antipsychotics can be predicted based on their ____ profiles at off-target receptors

A

binding

72
Q

t/f there do not seems to be patterns between typical and atypical antipsychotics in terms of binding profiles

A

t

73
Q

the most common ADR are ___ and ___ with drugs that also block histamine receptors

A

sedation and weight gain

74
Q

t/f anticholinergic effects are common with several antipsychotics

A

t

75
Q

hypotension may occur when drugs are used that block ___ receptors

A

alpha 1 adrenergic

76
Q

what off-target receptors can chlorpromazine bind to?

A

alpha 1, H1 and muscarinic

77
Q

what off-target receptors can haloperidol bind to?

A

alpha 1

78
Q

what off-target receptors can clozapine bind to?

A

alpha 1, H1, muscarinic

79
Q

what off-target receptors can olanzapine bind to?

A

H1

80
Q

what off-target receptors can aripiprazole bind to?

A

alpha 1, H1

81
Q

lithium has been used for many years as a ___

A

mood stabilizer

82
Q

lithium is used in the management of _____

A

bipolar affective disorder

83
Q

t/f the precise mechanism of how lithium stabilzes mood is unknown

A

t

84
Q

lithium can interact with ion ___ and ___. Why?

A

channels and transporters; bc it is a small monovalent cation like Na and K

85
Q

the proposed therapeutic mechanism of lithium involves the depletion of intracellular ____which influences many neuronal signalling pathway and also inhibiting ___which is involved in energy usage of cells

A

inositol; glycogen synthase kinase

86
Q

lithium is a classic example of a drug with a ___ therapeutic window

A

narrow

87
Q

too much lithium can lead to significant toxicity, including ___

A

life-threatening arrhythmias

88
Q

the neuronal ADRs of lithium are likely extensions of their therapeutic effects; by modifying neuronal function, ___ and ___ can occur

A

tremors and drowsiness

89
Q

at high levels of lithium, ___ can occur and in severe toxicity: ___ and ___ are possible

A

delirium, coma and death

90
Q

some ADR of lithium are related to its structural similarity to ___

A

sodium and potassium

91
Q

lithium’s ability to influence water and electrolyte balance in the kidneys can cause __ and ___

A

water retention and weight gain

92
Q

what are some cardiovascular effects that can occur wit high lithium doses? what is the severity?

A

tachycardia, hypotension, arrhythmias (life-threatening)

93
Q

what is the therapeutic range for lithium (in mEq/L)?

A

0.6-1.4

94
Q

t/f the ADR and need for constant monitoring with lithium use have made other antipsychotics and antidepressants more popular

A

treu

.Pharmacology (55 decks)

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