1- Antipsychotics & Mood Stabilizers/ Bipolar Affective Disorder Flashcards

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1
Q

Schizophrenia is characterized by hallucinations, delusions, disorganized thinking and emotional abnormalities. The positive sx of schizophrenia are due to what?

A

Overactive DA pathways in the limbic system

(negative sxs: affective behavior, apathetic, withdrawn, anti-social, lack of motivation, depressed)

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2
Q

Hallucinations (auditory > visual), catatonic behavior, disorganized speech and thinking are positive or negative sx of schizophrenia?

A

Positive

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3
Q

T or F: Schizophrenia does not lead to cognitive impairments?

A

FALSE! Cognitive impairments include: distracted, disorganized thought, memory loss

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4
Q

What is the mesolimbic DA pathway?

A

VTA to limbic system

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5
Q

What is the mesocortical DA pathway?

A

VTA to frontal cortex (cognition, emotion)

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6
Q

What is the Nigrostriatal DA pathway?

A

SN to striatum (motor control)

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7
Q

What is the tuberoinfundibular DA pathway?

A

Hypothalamus to pituitary (prolactin)

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8
Q

DA D2 receptors predominate in the mesolimbic system resulting in positive or negative sx?

A

Positive sx

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9
Q

DA D4 receptors predominate in the mesocortical regions resulting in positive or negative sx?

A

Negative sx

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10
Q

What is the MOA for typical antipsychotics?

A

Block DA D2 receptors (targets the mesolimbic sx to alleviate positive sx)

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11
Q

What class of drugs is used to decrease aggression, restlessness, and anxiety?

A

Antipsychotics (typical and atypical)

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12
Q

What class of drugs has a delayed onset of action (~6 wks), has sx persisting for weeks after last admin, and is metabolized by CYP450s?

A

Antipsychotics

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13
Q

What is the effect of prochlorperazine if used in low doses?

A

Antiemetic

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14
Q

SE are very common w/ the antipsychotic class. What are they?

A
  1. Decreased seizure threshold
  2. Endocrine- weight gain, increased prolactin
  3. Dental- xerostomia, bruxism (teeth grinding)
  4. Extrapyramidal sx
  5. Tardive dyskinesia
  6. Neuroleptic malignant syndrome
  7. Autonomic- anticholinergic, a-adrenergic, histamine
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15
Q

What is the tx for EPS sx (tremor, slurred speech)?

A

Tx w/ anticholinergics

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16
Q

Are EPS sx more common w/ typical or atypical antipsychotics?

A

Typical

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17
Q

Neuroleptic malignant syndrome is life threatening. What is the tx?

A

TX w/ Dantrolene

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18
Q

Antipsychotics will interact with anticholinergic drugs resulting in what?

A

More SE

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19
Q

Antipsychotics will interact with Sedative-hypnotics resulting in what?

A

Increased sedation

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20
Q

Antipsychotics will interact with TCAs resulting in what?

A

Seizures and cardiac effects

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21
Q

Why will antipsychotics interact unpredictably with antihypertensive meds

A

Due to alpha-blockade

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22
Q

Antipsychotics will interact w/ what meds?

A
  1. Anticholinergics
  2. Sedative-hypnotics
  3. TCAs 4.

Drugs that induce CYP450s

  1. Antihypertensive
  2. Tobacco (induces CYP450s)
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23
Q

What drug class is Chlorpromazine?

A

Typical antipsychotic

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24
Q

What drug class is Fluphenazine?

A

Typical antipsychotic

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25
Q

What drug class is Haloperidol?

A

Typical antipsychotic

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26
Q

When is chlorpromazine used?

A

Psychosis associated w/ mania and drugs of abuse, pre-anesthetic

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27
Q

What are the SEs of chlorpromazine?

A

Decreases seizure threshold, sedation, high anticholinergic effects (blurred vision decreased GI motility, inhibition of ejaculation) → low EPS, retinal deposits (browning of vision), postural hypotension, jaundice

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28
Q

What is the difference b/w Chlorpromazine and Fluphenazine?

A

Fluphenazine has less anticholinergic activity → moderate EPS

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29
Q

When is Haloperidol used?

A

Acute situations (very potent)

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30
Q

What are the pharmacokinetics of Haloperidol?

A

Long half life, IV

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31
Q

Haloperidol has no anticholinergic activity. What does this mean for EPS?

A

Lots of EPS

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32
Q

What is the MOA for atypical antipsychotics?

A

Block 5-HT2A and DA2 & DA4 receptors (alleviate negative and positive sx)

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33
Q

What areas of the brain does atypical antipsychotics target?

A

Targets mesocortical & mesolimbic system (alleviate negative and positive sx)

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34
Q

What area of the brain does typical antipsychotics target?

A

Targets mesolimbic systems (alleviates positive sx)

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35
Q

What is the MOA for Clozapine?

A

Block 5-HT2A and D2/4 receptors

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36
Q

What are the SEs of Clozapine?

A

Decreases seizure threshold, hypersalivation, sedation, dizziness, postural hypotension, tachycardia, weight gain

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37
Q

What atypical antipsychotic is the last DOC due to agranulocytosis?

A

Clozapine (blood must be monitored)

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38
Q

Are EPS and Tardive dyskinesia common or rare in Clozapine?

A

RARE

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39
Q

What will happen if Clozapine is abruptly discontinued?

A

Replase

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40
Q

What is the MOA for Olanzapine (Zyprexa)?

A

Atypical psychotic: Block 5-HT2A and DA2/4 receptors

41
Q

What are the other uses for Olanzapine (Zyprexa)?

A

Bipolar disorder, some anticholinergic activity

42
Q

What are the SEs of Olanzapine (Zyprexa)?

A

Hyperglycemia, T2DM (“Zyprexia DM”)

43
Q

Are EPS and Tardive dyskinesia common or rare in Olanzapine (Zyprexa)?

A

RARE

44
Q

What differentiates Olanzapine (Zyprexa) from Clozapine?

A

Olanzapine (Zyprexa) does not have agranulocytosis

45
Q

What is the MOA for Risperidone?

A

Atypical psychotic: Block 5-HT2A and DA D2/4 receptors

46
Q

What is the first line drug for psychosis?

A

Risperidone

47
Q

What are the SEs of Risperidone?

A

Hypotension

Weight gain

Insomnia

Anxiety

Lengthens QT interval

48
Q

Are EPS common or rare in Risperidone?

A

RARE

49
Q

What is the MOA for Ziprasidone?

A

Atypical psychotic: Block 5-HT2A and DA D2/4 receptors

50
Q

What are the additional used for Ziprasidone?

A

Tourettes syndromes Acute mania Some antidepressant activity

51
Q

How is Ziprasidone metabolized?

A

Metabolized by CYP3A4

52
Q

What are the SE of Ziprasidone?

A

Prolonged QT interval, sedation, impairs cognitive and motor skills

53
Q

In what population is Ziprasidone given w/ caution?

A

In pts w/ hx of seizure or drugs that decrease seizure threshold

54
Q

What is the MOA for Aripiprazole?

A
  1. Atypical psychotic: Partial agonist for DA D2/4 and 5-HT1A, Antagonist for 5-HT2A 2. Dopamine system stabilizer
55
Q

What does it mean that Aripiprazole is a DA system stabilizer?

A
  • Activates DA receptors if Dopaminergic tone is low - Blocks DA receptors if dopaminergic tone is high
56
Q

What is the use for Aripiprazole?

A

Modulates dopamine activity

57
Q

What is Aripiprazole metabolized by?

A

Metabolized by CYP3A4 and 2D6

58
Q

What are the SEs of Aripiprazole?

A

Decreased esophageal motility, hyperglycemia, seizures, sedation, increased glucose, postural hypotension

59
Q

Are EPS high or low in Aripiprazole?

A

LOS

60
Q

What is benefit of Ariprazole vs Ziprasidone and Risperidone?

A

Ariprazole does not lengthen QT interval

61
Q

What drugs do not increase prolactin?

A

Ariprazole & Quetiapine

62
Q

What is MOA for Quetiapine?

A

Atypical psychotic: Block 5-HT2A and DA D2/4 receptors

63
Q

What is the use of Quetiapine?

A

Promotes sleep onset and maintenance

64
Q

What are the SEs of Quetiapine

A

Very sedating, dizziness, constipation, xerostomia, postural hypotension, weight gain

65
Q

Are EPS common or rare w/ Quetiapine?

A

RARE

66
Q

What drugs have do not cause agranulocytosis? (3)

A

Quetiapine, Olanzapine, Lurasidone

67
Q

What is the MOA for Lurasidone?

A
  1. Atypical psychotic: Block 5-HT2A and DA D2/4 receptors 2. partial agonist for 5-HT1A
68
Q

What is the use of Lurasidone?

A

Tx of depression associated w/ bipolar disorder

69
Q

What are the SEs of Lurasidone?

A

Some incidence of agranulocytosis & neutropenia (blood counts should be monitored)

70
Q

What drug has not antihistamine or antimuscarinic effects?

A

Lurasidone

71
Q

In what disease does a pt alternate b/w manic phases to very deep depression?

A

Bipolar disorder

72
Q

Bipolar disorder is due to a lack of what NT activity?

A

GABAergic actvitiy

73
Q

How is Bipolar disorder generally treated?

A

With a combo of meds

74
Q

What is the MOA for lithium?

A

suppress 2nd messengers (IP3)

75
Q

What is DOC for tx of bipolar disease?

A

Lithium

76
Q

Does Lithium have a greater impact on mania or depressed sx?

A

Mania

77
Q

What medication is absorbed by the gut → not metabolized → excreted by kidneys w/ a t ½ = 24 hrs?

A

Lithium

78
Q

Where in the kidney is Lithium reabsorbed?

A

PCT

79
Q

What is the impact of the Lithium being reabsorbed by the PCT?

A

Competes w/ Na reabsorption

80
Q

If Na decreases, Li absorption increases. What effect does this have on Li?

A

Lithium toxicity

81
Q

If Na increases → LI absorption decreased. What effect does this have on Lithium?

A

Increased excretion of Li

82
Q

If Li increased → Na absorption decreases. What effect does this have on Na?

A

Hyponatremia

83
Q

What does does Li interact with?

A
  1. Antidepressants 2. Diuretics 3. NSAIDS 4. Sodium
84
Q

What is the drug interaction b/w Li and antidepressants?

A

Increases mania

85
Q

What is the drug interaction b/w Li and diuretics?

A

Alters salt excretion & Li clearance

86
Q

What is the drug interaction b/w Li and NSAIDs?

A

Increase Li toxicity (decrease clearance, increase Li uptake)

87
Q

What is the drug interaction b/w Li and Na?

A

Reduces Li concentration

88
Q

Why does Li have a high # of SEs?

A

Very small therapeutic window

89
Q

Li can cause what disease states?

A

Hypothyroidism, Diabetes Insipidus (Li inhibits ADH)

90
Q

What is the TX for Li induced DI?

A

Tx w/ amiloride (blocks Li into collecting duct)

91
Q

In what population in Li C/I?

A

Pregnancy

92
Q

What anticonvulsants can be used in the tx of bipolar disorder?

A

Valproic acid, Gabapentin, Carbamazepine, Lamotrigine

93
Q

What is the use of Valproic acid in the tx of bipolar disorder?

A

Rapid cycling manic/depressive phases (4-5 x/yr)

94
Q

What is the benefit of using Valproic acid to tx bipolar disorder?

A

Rapid onset of action (w/ equal or greater efficacy to Li)

95
Q

What is the use of Gabapentin in the tx of bipolar disorder?

A

Rapid cycling manic/depressive phases (4-5 x/yr)

96
Q

What is the use of Carbamazepine for the tx of bipolar disorder?

A

Refractory bipolar disorder (used in combo w/ Li)

97
Q

What is the use of Lamotrigine in the tx of bipolar disorder?

A

Prevention of relapse, depressive state following mania, acute mania

98
Q

Carbamazepine increases the toxicity of what drugs?

A

Increases toxicity of cimetidine, isoniazid, fluoxetine, erythromycin