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Pharmacology II Exam 1 > Antipsychotics > Flashcards

Antipsychotics Flashcards

1
Q

What is the dopamine hypothesis of schizophrenia that underlies positive symptoms?

A

Excess of mesolimbic dopamine activity (evidence: increased dopamine aggravates schizophrenia & most neuroleptics block D2 receptors or deplete dopamine)

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2
Q

What is the dopamine hypothesis of schizophrenia that underlies negative symptoms and cognitive dysfunction?

A

What is the dopamine hypothesis of schizophrenia that underlies negative symptoms and cognitive dysfunction?

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3
Q 
Which dopaminergic pathway is involved with eating behavior? Its blockade produces anti-emetic effects.
A. Tuberoinfundibular
B. Nigrostriatal
C. Mesolimbic-mesocortical
D. Medullary-periventricular
A

d

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4
Q 
Which dopaminergic pathway is involved with coordination of movement? Its blockade produces parkinsonian side effects.
A. Tuberoinfundibular
B. Nigrostriatal
C. Mesolimbic-mesocortical
D. Medullary-periventricular
A

b

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5
Q 
Which dopaminergic pathway is involved with prolactin secretion? Its blockade causes hyperprolactinemia & sexual side effects.
A. Tuberoinfundibular
B. Nigrostriatal
C. Mesolimbic-mesocortical
D. Medullary-periventricular
A

a

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6
Q 
Which dopaminergic pathway is involved with emotional and cognitive circuitry? Its blockade produces antipsychotic efficacy.
A. Tuberoinfundibular
B. Nigrostriatal
C. Mesolimbic-mesocortical
D. Medullary-periventricular
A

c

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7
Q

All antipsychotic drugs, with the exception of _____, all are considered equally efficacious in the treatment of schizophrenia.

A

Clozapine (atypical)

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8
Q

T/F: Typical and atypical antipsychotics both treat positive symptoms of schizophrenia, but atypical drugs generally have better efficacy and tolerability.

A

False- both groups are effective but atypical drugs generally have better side effect profiles

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9
Q

Side effect profile of typical antipsychotics (vs. atypical)

A

Extrapyramidal side effects and tardive dyskinesia (vs. lower risk of EPSE/TD and higher risk of weight gain & metabolic effects)

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10
Q

Side effect profile of atypical antipsychotics (vs. typical)

A

Lower risk of EPSE/TD but higher risk of weight gain and metabolic effects

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11
Q

Which class is more effective for treatment of negative symptoms and cognitive dysfunction?
A. Typical
B. Atypical
C. Neither treat negative symptoms with much efficacy
D. Both groups are effective

A

b

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12
Q

What is the MOA of antipsychotics?

A

Dopamine D2 receptor antagonists

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13
Q

D2 binding affinity of typical drugs is highly correlated with clinical potency. What % of receptor occupancy is required to exert antipsychotic effects?

A

60%

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14
Q

What unique MOA of atypical antipsychotics underlies their negative symptoms efficacy and accounts for their lower risk for EPSE?

A

Inverse agonist activity at 5-HT2A receptors and affinity 5-HT2A > D2

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15
Q

How long does therapy take to achieve full benefit in acute/chronic psychotic disorders and mania?

A

4-6 weeks

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16
Q

In what percentage of patients is antipsychotic treatment effective?

A

70%

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17
Q

What are the 2 non-psychotic uses of antipsychotics?

A

Antiemetic, sedative

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18
Q

T/F: Psychiatric use of typical drugs has expanded to major depression, anxiety, OCD, PTSD, and delusional parasitosis.

A

False- atypical drugs have

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19
Q

Which of the following is NOT true regarding antipsychotic PK?
A. Highly hydrophilic with small Vd
B. Effective with once daily dosing
C. Onset is rapid (hours), but it may take weeks to achieve maximal drug response
D. Long half-lives (20-40 hour

A

A (highly lipophilic and large Vd - cross the BBB duh!)

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20
Q

T/F: Antipsychotics can be given orally or parenterally, including a depot IM preparation.

A

True (oral dissolving too!)

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21
Q 
Antipsychotics are metabolized by which of the following CYP enzymes?
A. 3A4, 2C19
B. Phase 2 conjugation only
C. 2C9, 2D6
D. 2D6, 3A4
A

d

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22
Q

Boxed warning for antipsychotics

A

Increased mortality in elderly with dementia-related psychosis

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23
Q

What are the adverse metabolic effects (most commonly seen with 2nd generation drugs)?

A

Dyslipidemia, diabetes

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24
Q

What potentially fatal cardiac side effect occurs with antipsychotics?

A

QT interval prolongation

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25
Q 
EPSE is an adverse effect of antipsychotics, especially with increased doses (>80% D2 receptor occupancy). Which symptom is the most common & is described as restlessness?
A. Tardive dyskinesia 
B. Akathesia
C. Dystonias
D. Parkinsonism
A

b

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26
Q 
EPSE is an adverse effect of antipsychotics, especially with increased doses (>80% D2 receptor occupancy). Which symptom includes tremor, rigidity, shuffling gait, & slow movements?
A. Tardive dyskinesia 
B. Akathesia
C. Dystonias
D. Parkinsonism
A

d

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27
Q 
EPSE is an adverse effect of antipsychotics, especially with increased doses (>80% D2 receptor occupancy). Which symptom features acute muscle spasms of neck, back, & eyeballs?
A. Tardive dyskinesia 
B. Akathesia
C. Dystonias
D. Parkinsonism
A

c

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28
Q 
EPSE is an adverse effect of antipsychotics, especially with increased doses (>80% D2 receptor occupancy). Which symptom occurs after chronic use of > 6 months, may be irreversible, and includes oral-facial dystonias & chorioathetosis?
A. Tardive dyskinesia 
B. Akathesia
C. Dystonias
D. Parkinsonism
29
Q 
Which EPSE symptom is treated with anticholinergics or anti-parkinsonian agents? Select all that apply.
A. Tardive dyskinesia 
B. Akathesia
C. Dystonias
D. Parkinsonism
E. None of these
30
Q 
Which EPSE symptom is treated with dose reduction, BZD, or a beta blocker?
A. Tardive dyskinesia 
B. Akathesia
C. Dystonias
D. Parkinsonism
31
Q 
Which EPSE symptom cannot be treated- only prevented?
A. Tardive dyskinesia 
B. Akathesia
C. Dystonias
D. Parkinsonism
32
Q

3 autonomic side effects

A

Anticholinergic (dry mouth, constipation), anti-adrenergic (a1- orthostatic hypotension), anti-histaminergic (H1- sedation & weight gain)

33
Q

What effect explains the sexual side effects of antipsychotics? What are 4 examples of these side effects?

A

Hyperprolactinemia; hypogonadism, infertility, gynecomastia, amenorrhea

34
Q

T/F: Neuroleptic malignant syndrome is most common with atypical drugs, but occurs with typical drugs as well.

A

False- most common with typical

35
Q

What is the tetrad of neuroleptic malignant syndrome?

A 
Mental status change (confusion)
Hyperthemia (> 40C = 104F)
Extreme muscle rigidity (increased CK)
Autonomic dysfunction (tachycardia, sweating, HTN)
36
Q

If neuroleptic malignant syndrome occurs, what is the treatment?

A

Drug withdrawal and supportive care

37
Q

If neuroleptic malignant syndrome occurs, can the patient re-start an antipsychotic again?

A

Yes, can restart cautiously (not the same drug tho)

38
Q

What are the 2 subclasses within the first generation drugs?

A

High potency and low potency (for D2 receptor blocking)

39
Q

What is the difference between high potency and low potency drugs? Is this sub-division in typicals or atypicals?

A

Higher potency= higher risk of EPSE but less sedating (lower potency= lower risk EPSE, more sedating); typicals (1st generation)

40
Q

Classify- haloperidol (Haldol)
Typical or atypical?
Sub-division?

A

Typical, high potency

41
Q 
Which of the following is NOT a use of haloperidol?
A. Intractable hiccups
B. Schizophrenia
C. Tics/vocalizations in Tourette's
D. OCD
A

A (use for chlorpromazine - typical, low potency)

42
Q

Which of the following is a use of haloperidol (high potency) AND chlorpromazine (low potency)?
A. ICU for delirium
B. Severe behavioral problems in children
C. Huntington’s chorea
D. Tourette’s disorder

A

B (A= halo, C= chlor, D= halo)

43
Q

T/F: Haloperidol & chlorpromazine can be used for nausea/vomiting.

A

True (high potency & low potency typical drugs)

44
Q

Used off label to control behavior in elderly with dementia

A

Chlorpromazine (low potency -more sedating- typical)

45
Q

Classify- clozapine
Typical or atypical?
Sub-class?

A

Atypical (no sub-class)

46
Q

Unique use for clozapine

A

Recalcitrant schizophrenia and suicidal behavior in patients with schizoaffective disorder (mental disorder with features of schizophrenia and a mood disorder like major depression or bipolar)

47
Q

How long does it take to full respond to clozapine?

A

6 months or more

48
Q

What is the significant advantage of clozapine?

A

Nearly absent risk of EPSD/TD (but reserved for cases where other antipsychotics have failed due to side effects)

49
Q

5 boxed warnings of clozapine

A

Agranulocytosis, CVE, seizures, hypersalivation

50
Q

Aripiprazole MOA

A

Partial agonism (25%) of D2 receptors blocks full agonist effect of dopamine, also blocks 5-HT2A (like other atypicals)

51
Q 
Which of the following has expanded therapeutic use to bipolar disorder and major depression disorder?
A. Clozapine
B. Haloperidol
C. Chlorpromazine
D. Aripiprazole
A

D (atypical, partial D2 agonist + blocks 5-HT2A)

52
Q 
Which of the following would have more metabolic disorders associated with it? Select all that apply.
A. Chlorpromazine
B. Clozapine
C. Haloperidol
D. Aripiprazole
A

B, D (2nd generation= more metabolic ADEs)

53
Q 
Which of the following would have the HIGHEST risk of EPSE/TD?
A. Chlorpromazine
B. Olanzapine
C. Quetiapine
D. Haloperidol
A

D (typical high potency > typical low potency > atypical)

54
Q

T/F: There is no convincing data to suggest superior efficacy of any one agent so choice is based on patient tolerability, prior response, and physician preference.

55
Q 
Which drug would most likely be selected for a monotherapy trial of 4-6 weeks?
A. Clozapine
B. Haloperidol
C. Aripiprazole
D. Chlorpromazine
A

C (the atypical we have to know but also quetiapine, risperidone, & ziprasidone)

56
Q

Why would typical agents be preferred over atypical agents?

A

Patients with prior treatment response with no EPSE, cost, availability

57
Q

What defines refractory schizophrenia?

A

Failure of at least 2 monotherapy trials

58
Q

What, if anything, can treat refractory schizophrenia?

A

Clozapine (effective in 30-60% of patients)

59
Q

Though commonly used, antidepressants for the treatment of ____ are controversial due to lack of benefit and potential harm.

A

Bipolar disorder (might cause rapid mood switching)

60
Q

4 drug classes to treat mania:

A
  • Lithium
  • anti-seizure drugs (valproate, carbamazepine), second generation antipsychotics
  • benzodiazepines as add-on (for agitation
  • insomnia, anxiety)
61
Q 
Which of the following could you use to treat severe acute mania? Select all that apply.
A. Valproate or benzodiazepine
B. Benzodiazepine + lithium
C. Valproate + 2nd gen. Antipsychotic
D. Lithium + 2nd gen. Antipsychotic
62
Q

Which of the following could you use to treat mild-moderate mania (hypomania)? Choose the best/first-line answer.
A. Monotherapy with atypical antipsychotic
B. Lithium
C. Valproate + atypical antipsychotic
D. Better not to treat- watchful waiting

63
Q

MOA: Inhibits neuronal signaling pathways via inositol phosphate 3 (IP3), thus reduces GPCR synaptic transmission
Inhibits glycogen synthase kinase-3 activity

A

Lithium (mood stabilizer)

64
Q 
Which of the following describes lithium effect?
A. Causes mania in normal individuals
B. Reduces mania in bipolar patients
C. Reduces hypomania in bipolar patients
D. All are correct
A

B (no effect on normal individuals)

65
Q

T/F: Lithium is NOT eliminated renally.

A

False- dosed according to CrCl

66
Q

Lithium is monitored to prevent toxicity, as it has a narrow therapeutic index (target: 0.8-1.2 mEq/L). Which of the following is NOT an acute adverse effect seen at therapeutic doses?
A. Hypercalcemia & hyperparathyroidism
B. Nausea, diarrhea
C. Weight gain
D. Tremor
E. All of these are acute adverse effects @ therapeutic doses

A

A (long-term effect @ therapeutic dose)

67
Q

Lithium is monitored to prevent toxicity, as it has a narrow therapeutic index (target: 0.8-1.2 mEq/L). Which of the following is NOT an acute adverse effect seen at therapeutic doses?
A. Nausea, diarrhea
B. Thyroid dysfunction
C. Mild cognitive impairment
D. Polyurea & polydipsia
E. All of these are acute adverse effects @ therapeutic doses

A

B (long-term effect @ therapeutic doses)

68
Q

Lithium is monitored to prevent toxicity, as it has a narrow therapeutic index (target: 0.8-1.2 mEq/L). Which of the following is NOT a long-term adverse effect seen at therapeutic doses?
A. Hypercalcemia & hyperparathyroidism
B. Nephrogenic diabetes insipidus
C. Mild cognitive impairment
D. Arrhythmias in patients with preexisting CV disease
E. All of these are long-term adverse effects @ therapeutic doses

69
Q

Lithium levels > 2 mEq/L can result in toxic overdose. Risk increases with 1) renal impairment 2) dehydration 3) sodium depletion. How does this present? (3)

A

Nausea/vomiting/diarrhea, arrhythmias, neurologic (lethargy, ataxia, confusion, seizures)

Pharmacology II Exam 1 (9 decks)

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