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Pharmacology Test #6 > Antipsychotics > Flashcards

Antipsychotics Flashcards

1
Q

Late onset schizophrenia affects

A

post-menopausal women

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2
Q

Positive symptoms of schizophrenia (psychosis)

A

auditory/visual hallucinations, delusions

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3
Q

Negative symptoms of schizophrenia

A

withdrawal, reduced speech, interest, drive, attention, and pleasure

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4
Q

cognitive deficits with schizophrenia

A

attention, memory, executive function

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5
Q

Onset of schizophrenia

A

late adolescence (males earlier than females)

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6
Q

Core symptom of schizophrenia

A

cognitive dysfunction

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7
Q

Etiology of schizophrenia

A

complex interactions between genetic predisposition and environmental risk

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8
Q

Specific genes associated with schizophrenia

A 
COMT - catecholine metabolism;
DISCI - cell morphology, migration;
DTNBPI - axon stability;
GABRB2 - GABA system;
NRGI - cell growth and differentiation
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9
Q

Environmental risks for schizophrenia

A
  1. obstetrical complications (hemorrhage, pre-term, nutrtion, maternal stress)
  2. infections and/or inflammation (more schizo for winter pregnancies and flu epidemics)
  3. cannabis (COMT mutations
  4. immigration (stress?)
    5 smoking rates
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10
Q

What percentage of schizophrenics are smokers?

A

75-90%

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11
Q

Dopamine hypothesis of schizophrenia

A

psychosis or psychotic symptoms are due to a hyperactive DA system/signaling

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12
Q

5 pieces of evidence for the DA hypothesis

A
  1. Correlation between clinical effectiveness and affinity at D2
  2. PRO-DA agents in Parkinson’s can produce psychosis
  3. Increased D2 density in schizophrenia
  4. Increased DA release in schizophrenia and increased DA receptor occupancy
  5. Odd changes in DA metabolism following administration of D2-directed antipsychotics
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13
Q

Evidence against the dopamine hypothesis

A
  1. D2 antagonists are not universally effective
  2. Atypicals - lower D2 affinity and added serotonin pharmacology
  3. Blocking NMDA receptors produces psychosis
  4. Widespread anatomical abnormalities
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14
Q

What does smoking alter?

A

Smoking alters DA transmission

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15
Q

First antipsychotic that worked well

A

Chlorpromazine

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16
Q

First atypical antipsychotic

A

Clozapine

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17
Q

General progression from typicals to atypicals reflects

A
  1. Better affinity at D2 receptors
  2. Addition of activity at 5HT2A and others
  3. Better control over negative and cognitive Sx
  4. Fewer EPS
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18
Q

Selectivity of Chlorpromazine

A

hits multiple targets that are not desirable

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19
Q

Haldol selectivity

A

more selective blocker for D2 than chlorpromazine

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20
Q

Difference between D1-like and D2-like receptors

A

D1-like (D1 and D5) are Gs-coupled (increased cAMP) whereas D2-like (D2, D3, and D4) receptors are Gi-coupled

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21
Q

Dopamine system comprises

A

dopamine-producing cells in the VTA and substantia nigra pars compacta

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22
Q

DA circuits involved in the therapeutic and cognitive activities of D2 antagonists

A

the mesocortical and mesolimbic pathways

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23
Q

Basal ganglia pathway important for motor control

A

nigrostriatal DA pathway from SNc to dorsal striatum

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24
Q

Circuit that extrapyramidal symptoms arise from

A

the nigrostriatal DA pathway from SNC to the dorsal striatum

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25
Q

Manipulation of the dopamine pathway in the hypothalamus causes

A

hyperprolactinemia

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26
Q

Manipulation of the dopamine pathway in the medulla is involved in

A

the anti-emetic properties of some antipsychotics

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27
Q

Efficacy of drugs is likely a combination of

A

direct antagonism and some long term adaptive changes

28
Q

Adaptive changes known to occur with dopamine antagonists

A

upregulation of D2 receptors

29
Q

1st generation antipsychotics

A

Phenothiazines and haloperidol

30
Q

Features of 1st generation antipsychotics

A
  1. Strong D2 antagonism
  2. Variable off-target effects
  3. Long half life
  4. Only (+) symptom control
31
Q

Features of Atypical 2nd generation antipsychotics

A
  1. Acquisition of 5HT pharmacology
  2. variable on/off kinetics at D2 receptor (vs. 1st gen)
  3. better mangement of cognitive Sx
  4. Occupation of other receptors
  5. Lower risk of EPS
32
Q

What kind of agonist is Aripirazole?

A

D2 partial agonist with potent 5HT2 inverse agonism

33
Q

What kind of antagonist is Haloperidol?

A

D2 antagonist

34
Q

Is complete D2 blockage necessary for antipsychotic efficacy?

A

No, partial agonism/antagonism may, with 5HT2 effects, be desirable clinically

35
Q

Classical and Early Atypical drugs

A

Clorpromazine
Haloperidol
Thioridazine
Sulpiride

36
Q

Novel Atypical drugs (Acquisition of 5HT pharm)

A 
Clozapine
Risperidone
Olanzapine
Ziprasidone
Quetiapine
Aripiprazole
37
Q

How do you manage schizophrenia in the first few days?

A

control initial/acute agitation with haldol injections

38
Q

How do you manage schizophrenia within days 7-14?

A

begin to address the positive symptoms, begin to transition from injection to po route of administration

39
Q

How do you manage schizophrenia long-term?

A

address the negative symptoms, maintain compliance, prevent relapse

40
Q

Overall treatment goals of schizophrenia

A
  1. control positive symptoms
  2. prevent relapse once stabilized
  3. reduce severe depression
  4. address cognitive dysfunction
41
Q

Other uses of atypical antipsychotics

A
  1. Refractory depression
  2. Bipolar depression
  3. Tourette’s syndrome
  4. OCD
  5. PTSD
  6. Personality disorder
  7. Autism
  8. Agitation in dementia
42
Q

Atypical antipsychotics for bipolar depression

A

Quetiapine and olanzapine

43
Q

Atypical antipsychotics NOT for bipolar depression

A

Aripiprazole and ziprasodone have no benefit

44
Q

Atypical antipsychotics for Tourette’s syndrome

A

Fluphenazine

45
Q

Atypical antipsychotic NOT for Tourette’s

A

Haloperidol not preferred

46
Q

Dystonia

A

muscle spasms of neck and eyes

47
Q

Akathesia

A

motor restlessness

48
Q

Parkinsonism

A

rigidity, shuffling gait, decreased facial expression

49
Q

Tardive dyskinesia

A

delayed, severe, embarrassing, irreversible uncontrolled movements

50
Q

Neuroleptic Malignant syndrome

A

EPS, fever, cognitive impairment

51
Q

What is Neuroleptic malignant syndrome treated with

A

direct DA agonists and muscle relaxants

52
Q

Why do atypicals show lower incidence of inducing EPS?

A

They have faster OFF kinetics at D2 receptors compared to typicals

53
Q

Describe how parkinsonism develops with antipsychotics

A

Strongly blocking D2 receptors causes reduced dopamine from SNc and therefore overactivity of indirect pathway striatal neurons, reduced activity of GPe, and overactivity of the STN. This overexcites the Gpi and SNr, which then over-inhibits the thalamus, which then causes reduced activation of the cortex

54
Q

Neuroleptic side effects of antipsychotics

A

Emotional: apathy and dysphoria
Cognitive: impaired thinking

55
Q

Endocrine side effects of antipsychotics

A

prolactin mediated (increased prolactin secretion, galactorrhea, sexual dysfunction, amenorrhea)

56
Q

Metabolic side effects of antipsychotics

A

weight gain, diabetes

57
Q

Hematologic side effects of antipsychotics

A

Agranulocytosis (early atypicals)

58
Q

Anticholinergic side effects of antipsychotics

A

dry mouth, urinary retention, constipation, blurred vision, sinus tachycardia, confusion, memory impairment

59
Q

Antihistamine side effects of antipsychotics

A

sedation and confusion

60
Q

Antiserotonin side effects of antipsychotics

A

weight gain

61
Q

Alpha1-adrenergic antagonism effects of antipsychotics

A

orthostatic hypotension, reflex tachycardia

62
Q

Notable side effects of Haloperidol

A

severe EPS

63
Q

Notable side effects of Olanzapine

A

weight gain

64
Q

Notable side effects of Clozapine

A

weight gain, sedation, anticholinergic Sx, adrenergic Sx

65
Q

Ideal Antipsychotic drug

A

Decrease positive symptoms; no EPS effects; no tardive dyskinesia; decrease in negative symptoms; improve cognitive deficits

66
Q

what kind of drugs are the current standard of care for schizophrenia

A

Atypicals (but are usually not better than typicals for positive Sx and they’re more expensive)

Pharmacology Test #6 (12 decks)

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