Chapter 15: Schizophrenia and Bipolar Affective Disorder

Question 1

what are the 2 categories of antipsychotics?

Answer 1

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

Question 2

mania or a manic episode is characterized by:

Answer 2

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

Question 3

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

Answer 3

psychosis

Question 4

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

Answer 4

mania and depression

Question 5

what is psychosis?

Answer 5

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

Question 6

___ is the most common clinical presentation of psychosis?

Answer 6

schizophrenia

Question 7

how does psychosis present in schizophrenia?

Answer 7

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

Question 8

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

Answer 8

genetic; relative

Question 9

schizophrenia occurs in ~__% of the population

Answer 9

1

Question 10

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

Answer 10

acute

Question 11

___ drugs are used to treat conditions where psychosis occurs

Answer 11

antipsychotic

Question 12

the 2 important NT involved in schizophrenia are __ and __

Answer 12

DA and 5-HT

Question 13

the DA hypothesis of schizophrenia proposes:

Answer 13

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

Question 14

the serotonin hypothesis of schizophrenia proposes:

Answer 14

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

Question 15

the glutamate hypothesis of schizophrenia proposes:

Answer 15

modified glutamate signalling contributes to dystregualtion of neuronal circuits

Question 16

what is the general consensus around the hypotheses of schizophrenia?

Answer 16

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

Question 17

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

Answer 17

1. mesolimbic

2. mesocortical

Question 18

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

Answer 18

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

Question 19

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

Answer 19

increases; D2; +

Question 20

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

Answer 20

delusions and hallucinations

Question 21

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

Answer 21

nucleus accumbens

Question 22

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

Answer 22

indirectly

Question 23

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

Answer 23

disinhibition

Question 24

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

Answer 24

nucleus accumbens

Question 25

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

Answer 25

nucleus accumbens

Question 26

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

Answer 26

D2

Question 27

blocking ___receptors is the primary MOA of typical antipsychotics

Answer 27

D2

Question 28

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

Answer 28

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

Question 29

the nigrostriatal pathway goes from the ___ to the ___

Answer 29

substance nigra to the striatum

Question 30

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

Answer 30

Parkinson's-like movements

Question 31

the tuberoinfundibulnar pathway goes from the ___ to the ___

Answer 31

hypothalamus to pituitary

Question 32

the tuberinfundibular pathway is involved in regulation of ___hormones

Answer 32

endocrine

Question 33

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

Answer 33

prolactin; low libido, infertility, enlargement of breast tissue

Question 34

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

Answer 34

typical; extrapyramidal

Question 35

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

Answer 35

poor adherence

Question 36

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

Answer 36

chlorpromazine

Question 37

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

Answer 37

calming

Question 38

chlorpromazine was the first ___ antipsychotic agent in use

Answer 38

typical

Question 39

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

Answer 39

it was found that chlorpromazine blocked DA receptor s

Question 40

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

Answer 40

DA; psychosis

Question 41

the primary action of typical antipsychotics is to block ___

Answer 41

DA recepts

Question 42

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

Answer 42

reduces DA signalling, which alleviates hallucinations and delusions

Question 43

Haloperidol is an example of a ___ type drug

Answer 43

typical antipsychotic

Question 44

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

Answer 44

long-acting depot formulation (IM injections)

Question 45

why is an IM injection of Haloperidol beneficial?

Answer 45

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

Question 46

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

Answer 46

Haloperidol

Question 47

how often is an IM injection of Haloperidol given?

Answer 47

monthly

Question 48

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

Answer 48

binding affinity at the D2 receptor

Question 49

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

Answer 49

resolve the positive symptoms of schizophrenia

Question 50

the potency is measured by what phamacokinetics term?

Answer 50

ED50

Question 51

affinity is measured by what pharmacokinetics term?

Answer 51

K

Question 52

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

Answer 52

their potency is directly related to their binding affinity

Question 53

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

Answer 53

higher (lower ED50)

Question 54

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

Answer 54

no

Question 55

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?

Answer 55

it means dopamine is not the only contributor

Question 56

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

Answer 56

5-HT; DA

Question 57

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

Answer 57

mesocortical pathway

Question 58

atypical antipsychotics have more activity at ___ receptor that __ receptors

Answer 58

5HT; DA

Question 59

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

Answer 59

t

Question 60

atypical antipsychotics restore ___ inputs into the mesolimbic pathway

Answer 60

inhibitory

Question 61

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

Answer 61

atypical; 5HT and DA

Question 62

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

Answer 62

+ and - symptoms of schizophrenia

Question 63

MOA of Aripiprazole

Answer 63

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

Question 64

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

Answer 64

t

Question 65

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

Answer 65

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

Question 66

many ADR common to most antipsychotics are related to ___

Answer 66

blocking D2 in unintended regions of the brain

Question 67

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

Answer 67

extrapyramidal (EPS) which cause Parkinson-like effects

Question 68

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

Answer 68

affinity

Question 69

what branch of antipsychotics has reduced affinity for D2 receptors?

Answer 69

atypical

Question 70

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

Answer 70

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

Question 71

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

Answer 71

binding

Question 72

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

Answer 72

t

Question 73

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

Answer 73

sedation and weight gain

Question 74

t/f anticholinergic effects are common with several antipsychotics

Answer 74

t

Question 75

hypotension may occur when drugs are used that block ___ receptors

Answer 75

alpha 1 adrenergic

Question 76

what off-target receptors can chlorpromazine bind to?

Answer 76

alpha 1, H1 and muscarinic

Question 77

what off-target receptors can haloperidol bind to?

Answer 77

alpha 1

Question 78

what off-target receptors can clozapine bind to?

Answer 78

alpha 1, H1, muscarinic

Question 79

what off-target receptors can olanzapine bind to?

Answer 79

H1

Question 80

what off-target receptors can aripiprazole bind to?

Answer 80

alpha 1, H1

Question 81

lithium has been used for many years as a ___

Answer 81

mood stabilizer

Question 82

lithium is used in the management of _____

Answer 82

bipolar affective disorder

Question 83

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

Answer 83

t

Question 84

lithium can interact with ion ___ and ___. Why?

Answer 84

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

Question 85

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

Answer 85

inositol; glycogen synthase kinase

Question 86

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

Answer 86

narrow

Question 87

too much lithium can lead to significant toxicity, including ___

Answer 87

life-threatening arrhythmias

Question 88

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

Answer 88

tremors and drowsiness

Question 89

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

Answer 89

delirium, coma and death

Question 90

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

Answer 90

sodium and potassium

Question 91

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

Answer 91

water retention and weight gain

Question 92

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

Answer 92

tachycardia, hypotension, arrhythmias (life-threatening)

Question 93

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

Answer 93

0.6-1.4

Question 94

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

Answer 94

treu