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Psychiatry > Neuropsychopharmacology Lecture and Handout > Flashcards

Neuropsychopharmacology Lecture and Handout Flashcards

1
Q

What are the significant monoamines?

A

Catecholamines: Dopamine, NE, Epi
Trypatmines/indoleamines: 5-HT, melatonin
Histamine

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2
Q

What is the origin of norepinephrinergic neurons in the brain?

A

Locus coeruleus

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3
Q

What is the origin of serotonergic neurons in the brain?

A

Dorsal raphe nucleus

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4
Q

What is the origin of dopaminergic neurons in the brain?

A

Ventral tegmental area and substantia nigra

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5
Q

What is the dopaminergic pathway involved in cognition and executive function?

A

Mesocortical, VTA to dorsolateral prefrontal cortex

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6
Q

What is the dopaminergic pathway involved in emotions and affect?

A

Mesocortical, VTA to ventromedial PFC

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7
Q

What is the dopaminergic pathway involved in motivation, pleasure, and reward?

A

Mesolimbic, VTA to nucleus accumbens (limbic area)

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8
Q

What is the dopaminergic pathway involved in movement?

A

Nigrostriatal: Substantia nigra to basal ganglia and striatum

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9
Q

What is the dopaminergic pathway involved in prolactin regulation?

A

Tuberoinfundibular: hypothalamus to anterior pituitary (inhibits prolactin release)

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10
Q

What are the key dopaminergic pathways in the brain?

A
  1. Mesocortical: VTA to dorsolateral PFC
  2. Mesocortical: CTA to ventromedial PFC
  3. Mesolimbic: VTA to nucleus accumbens (limbic area)
  4. Nigrostriatal: Substantia nigra to basal ganglia and striatum
  5. Tuberoinfundibulur: hypothalamus to anterior pituitary
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11
Q

According to the dopamine hypothesis of schizophrenia, what dysfunction in what area of brain is responsible for positive symptoms? Negative symptoms?

A

Positive: Hyperactivity of mesolimbic pathway (VTA to nucleus accumbens)

Negative: Hypoactivity of mesocortical system (VTA to PFC)

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12
Q

What is the effect of D2 blockage on the mesolimbic pathway in a schizophrenic patient? (According to the dopamine hypthesis)

A

Reduction in positive symptoms

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13
Q

What is the effect of D2 blockage on the mesocortical pathway in a schizophrenic patient? (According to the dopamine hypothesis)

A

No benefit to negative symptoms

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14
Q

What is the effect of D2 blockage on the nigrostriatal pathway in a schizophrenic patient? (According to the dopamine hypothesis)

A

Extrapyrimadial side effects / parkinsonism

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15
Q

What is the effect of D2 blockage on the tuberoinfundibular pathway in a schizophrenic patient( According to the dopamine hypothesis)

A

Can lead to hyperprolactinemia and potentially prolactinoma

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16
Q

What are the types of extrapyramidal side effects?

A
  1. Dystonia
  2. Dyskinesia/akinesia/bradykinesia
  3. Akathisia
  4. Tremor
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17
Q

What can be involved in acute dystonic reaction EPS?

A

All are forms of involuntary increased muscle tone.

  1. Blepharospasm (involuntary eye closure)
  2. Oculogyric crisis (fixed upward or disconjugate gaze)
  3. Torticollis (twisted neck)
  4. Opisthonos (arching back)
  5. Layngospasm
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18
Q

What is the most common part of the body involved in tardive dyskinesia?
Where else can be involved less commonly?

A

Face/mouth most common (75% of cases)

Extremities (50%) and trunk (25%) can also be seen

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19
Q

What types of extremity movements can be seen in tardive dyskinesia?

A
  1. Tremors
  2. Rhythmic movements
  3. Choreoathetoid movements:
    a. Choreiform: jerky, spasmodic, quasi-purposeful
    b. Athetoid: slow, writhing, twisting
    c. Ballismus: violent sudden motions
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20
Q

What types of trunk movements can be seen in tardive dyskinesia?

A

Twisting, rocking, gyrating

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21
Q

What types of facial/oral movements can be seen in tardive dyskinesia?

A

Frowning, grimacing, puckering, lip smacking, chewing, teeth grinding, tongue tremor, tongue protrusion, tongue rolling

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22
Q

What medication can be used for akathisia?

A

Propanolol (one of few lipophilic beta blockers that crosses the blood-brain barrier)

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23
Q

What types of side effects can be seen from antipsychotics in general?

A
  1. Extrapyramidal side effects (some typicals and atypicals)
  2. Metabolic syndrome (atypicals)
  3. Anti-HAM symptoms:
    a. H1 block: sedation, weight gain
    b. Alpha-1 adrenergic block: orthostatic hypotension
    c. Antimuscarinic block: Memory impairment, confusion, cardiac (e.g. tachycardia), blurred vision, dry mouth, constipation.
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24
Q

What secondary target of some antipsychotics leads to reduced EPS?

A

Muscarinic receptors (ACh neurons modulate DA neurons in the nigrostriatal pathway only)

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25
Q

How strongly do haloperisol, fluphenazine, perphenazine, and chlorpromazine each block D2, M1, H1, and alpha1 receptors?

A

Haloperidol: specific high-potency D2 block
Fluphenazine: similar to haloperidol
Perhpenazine: high-potency D2 block, also significant H1 and alpha1 block, but low M1 block
Chlropromazine: moderate potency D2 block, significant block of M1, H1, and alpha1.

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26
Q

What are 4 typical antipsychotics?

A

Haloperidol (Haldol)
Fluphenazine (Proloxin)
Perphenazine (Trilafon)
Chlorpromazine (Throazine)

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27
Q

Which antipsychotics have the highest incidence of EPS?

A

Typicals: haloperidol, fluphenazine
Atypical: Risperidone

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28
Q

Which antipsychotics have long-acting forms?

A 
Typicals:
1. Haloperidol deconoate
2. Fluphenzaine decanoate
Atypicals:
1. Risperidone consta
2. Aripiprazole lauroxil
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29
Q

Which antipsychotics are most sedating?

A

Typical: Chlorpromazine (thorazine)
Atypical: Quetiapine (seroquel)

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30
Q

Which typical antipsychotic(s) has the most anti-cholinergic side effects?

A

Chlorpromazine (thorazine)

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31
Q

What typical antipyschotic(s) has the least EPS?

A

Chlorpromazine (thorazine) - because of ACH block

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32
Q

What are the two hypotheses as to why atypical antipsychotics tend to have fewer EPS and more efficacy for negative symptoms?

A

Serotonin-dopamine antagonism theory: 5-HT2 receptor blockage
“Fast off” theory: rapid dissociation from D2 receptors

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33
Q

What receptors are potentially involved in antipsychotic-related weight gain?

A

H1 and 5-HT2C blockage

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34
Q

What did the CATIE trial show about typical vs. atypical antipsychotics?

A

Perphenazine (Trilafon), the only typical studied, was as efficacious and well-tolerated as the atypicals

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35
Q

What atypical antipsychotic(s) is most associated with hyperprolactinemia?

A

Risperidone (Risperdal)

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36
Q

What are symptoms of hyperprolactinemia in women? Men?

A

Women: amenorrhea, galactorrhea
Men: decreased libido (early sign), gynecomastia

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37
Q

What atypical antipsychotic(s) is most associated with metabolic syndrome?

A

Olanzapine (Zyprexa), Clozapine (Clozaril)

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38
Q

What atypical antipsychotic(s) is most associated with akathisia?

A

Aripiprazole (Abilify)

The atypical antipsychotic that is activating rather than sedating

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39
Q

What is the only antipsychotic also approved as an adjunct antidepressant?

A

Aripiprazole (Abilify)

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40
Q

Which atypical antipsychotic(s) is more weight neutral?

A

Aripiprazole (Abilify), Ziprasidone (Geodon)

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41
Q

What atypical antipsychotic(s) is more activating rather than sedating?

A

Aripiprazole (Abilify)

Can activate too much and lead to akathisia

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42
Q

What atypical antipsychotic is most associated with orthostatic hypotension?

A

Quetiapine (Seroquel)

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43
Q

What atypical antipsychotic(s) can be useful as a sleep aid?

A

Quetiapine (Seroquel)

Also approved as a mood stabilizer

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44
Q

What atypical antipsychic(s) is approved as a monotherapy mood stabilizer?

A

Quetiapine (Seroquel)

Also can be used as sleep aid

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45
Q

What atypical antipsychotic(s) may be useful in bipolar depression?

A

Quetiapine (Seroquel)

Also approved as monotherapy mood stabilizer

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46
Q

What atypical antipsychotic is by far the worse for QT prolongation?

A

Ziprasidone (Geodon)

Rarely used for this reason as well as needed to be taken with a meal

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47
Q

What atypical antipsychotic(s) is associated with drooling?

A

Clozapine (Clozaril)

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48
Q

What atypical antipsychotic(s) is associated with agranylocytosis?

A

Clozapine (Clozaril)

Effective but dangerous - also decreases seizure threshold

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49
Q

What atypical antipsychotic(s) significantly lowers the seizure threshold?

A

Clozapine (Clozaril)

Effective but dangerous - also leads to agranulocytosis

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50
Q

What monoamines are broken down by MAO-A? MAO-B?

A

MAO-A: Serotonin, melatonin, Epi, NE, DA.
MAO-B: DA, phenylethylamine, trace amines

(Note that DA is broken down by both)

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51
Q

What MAOI is selective for MAO-B?

What is the implication of this?

A

Selegiline.

More specific for DA (does not break down 5HT, melatonin, Epi, or NE), so can be used in low dose to augment DA signaling in Parkinson’s with fewer side effects.

At higher doses blockes MAO-A as well, so can still be used as an antidepressant with higher dose.

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52
Q

What are 4 common MAOIs?

A

Phenelzine (Nardil)
Tranylcypromine (Parnate)
Isocarboxazid (Marplan)
Selegiline (MAO-B selective)

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53
Q

What are common side effects of MAOIs?

A

Orthostatic hypotension, sleep disturbence, GI distress, dry mouth, headache

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54
Q

What are the dangerous side effects of MAOIs?

A 
Serotonin syndrome
Hypertensive crisis (tyramine interaction)
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55
Q

What are symptoms of serotonin syndrome?

A

Flushing, diaphoresis, myoclonic jerks

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56
Q

Other than antidepressants, what are 4 serotonergic drugs that can contribute to serotonin syndrome?

A
  1. Linezolid (antibiotic against resistant gram-positives)
  2. Tramadol (opioid painkiller)
  3. Miperidime (Demerol, opioid painkiller)
  4. Dextromethorphan (cough suppressant opioid)
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57
Q

How is hypertensive crisis with MAOI tyramine interaction treated?

A

Phentolamine (alpha blockade)

Do NOT give beta blockers (without giving alpha blockers first), as this would lead to vasoconstriction due to unopposed alpha blockage.

58
Q

What type of antidepressant has significant dietary restrictions?

A

MAOIs (due to tyramine hypertensive crisis)

Tyramine in aged cheese, Chanti, fava beans, liver, cured meats, soy sauce, sauerkraut

59
Q

What is the on-target pharmacologic actions of tricyclic antidepressants?

Off-target?

A

On target: Inhibits NE and 5-HT reuptake

Off-ticked: Histamine, Muscarinic, Alpha-adrenergic blockade

60
Q

What MAOI has amphetamine-like properties?

A

Tranylcypromine (Parnate)

61
Q

What are common side-effects of TCAs?

A

Anti-HAM:

a. H1 block: sedation, weight gain
b. Alpha-1 adrenergic block: orthostatic hypotension
c. Antimuscarinic block: Memory impairment, confusion, cardiac (e.g. tachycardia), blurred vision, dry mouth, constipation.

62
Q

What are dangerous side-effects of TCAs?

A
  1. Cardiac conduction disruption, leads widened QRS, long QT, and arrhythmia)
  2. Lethal in overdose
63
Q

What drug effect is signified by widened QRS on EKG?

How is this treated?

A

TCA overdose (also see long QT).

Treatment: Sodium bicarbonate and magnesium

64
Q

What TCA is approved for insomnia treatment?

A

Doxepin

65
Q

What TCA is least likely to cause orthostatic hypotension?

A

Nortriptyline (Pamelor)

66
Q

What TCA is least sedating?

A

Desipramine (Norpramin)

also fewest anticholinergic side effects

67
Q

What TCA has the fewest anti-cholinergic side effects?

A

Desipramine (Norpramin)

also least sedating

68
Q

What TCA is the most 5-HT specific?

A

Clomipramine (Anafranil)

Incidentally, also used in treating OCD

69
Q

What TCA is also used in treating OCD?

A

Clomipramine (Anafranil)

Incidentally, also most 5-HT specific

70
Q

Other than depression, what can TCAs be used to treat?

A

Chronic pain, headache.

Clomipramine (Anafranil) can be used for OCD as well

71
Q

What are three TCAs?

A

Nortyrptyline (Pamelor)
Desipramine (Norpramin)
Clomipramine (Anafranil)
Others: Imipramine, Amitryptyline, Doxepin

72
Q

What SSRI has an extremely long half-life and therefore has no need to taper before stopping?

A

Fluoxetine (Prozac)

73
Q

What SSRI is considered relatively activating?

A

Fluoxetine (Prozac)

Can worsen anxiety

74
Q

What SSRI is considered relatively sedating?

A

Paroxetine (Paxil)

75
Q

What is the “dirtiest” SSRI with the most side effects in general?

A

Fluoxetine (Prozac)

Sexual dysfunction is particularly bad

76
Q

What SSRI is worst for sexual dysfunction?

A

Fluoxetine (Prozac)

77
Q

What SSRI(s) can worsen anxiety?

A

Fluoxetine (Prozac)

Relativley activating

78
Q

What SSRI(s) can be used in anxiety disorders?

A

Paroxetine (Paxil)

Sertraline (Zoloft)

79
Q

What SSRI(s) has a short-life and therefore significant discontinuation syndrome with missed doses?

A

Paroxetine (Paxil)
Sertraline (Zoloft)
Fluvocamine (Luvox) - so short it requires BID dosing.

80
Q

Compare and contrast Fluoxetine and Paxil in terms of:

  1. Activation/sedation
  2. Effect on anxiety
  3. Half-life
A

Fluoxetine: Activating, can worsen anxiety, long half-life (no need to taper doses before stopping)

Paroxetine: Sedating, can be used in anxiety disorders, short half-life (discontinuation syndrome)

81
Q

What SSRI(s) have few drug-drug interactions?

A

Sertraline (Zoloft)
Citalopram (Celexa) and Escitalopram (Lexapro)
(Newer drugs)

82
Q

What SSRI tends to cause more GI upset when starting?

A

Sertraline (Zoloft)

83
Q

What SSRI has a very low incidence of common SSRI-related side effects?

A

Citalopram (Celexa)

Except can prolong QTc

84
Q

What SSRI can lead to QT prolongation?

A

Citalopram (Celexa)

Otherwise few side effects

85
Q

What are common side effects of SSRIs?

A

Sexual dysfunction, GI upset, headache.

86
Q

What SSRI is actually not approved for depression?

What is is approved for?

A

Fluvoxamine (Luvox)

Approved for OCD and social anxiety disorder.

87
Q

What are 4 SSRIs approved for depression?

A

Fluoxetine (Prozac)
Paroxetine (Paxil)
Sertraline (Zoloft)
Citalopram (Celexa) / Escitalopram (Lexapro)

(Fluvoxamine (Luvox) is not approved for depression, instead for OCD and social anxiety)

88
Q

What are two SNRIs?

A

Venlafaxine (Effexor)

Duloxetine (Cymbalta)

89
Q

What else can SNRIs potentially help with?

A

Chronic pain

90
Q

In what patients is the SNRI contraindicated in?

A

Poorly controlled hypertension

91
Q

What is the mechanism of action of buproprion?

A

NDRI: NE/DA reuptake inhibitor

92
Q

How do side effects of SNRIs compare to SSRIs, in general?

A

Similar. May be more activating than most SSRIs.

93
Q

What are the advantages of buproprion?

A
  1. Rarely has sexual side effects
  2. Can help stop smoking.
  3. Relatively activating (but can worsen anxiety)
94
Q

What are the disadvantages of buproprion?

A
  1. Can worsen anxiety (relatively activating)
  2. Lowers seizure threshold, CI in epilepsy
  3. CI in eating disorder patients
95
Q

What is the mechanism of action of mirtazapine?

A

NaSSA: Noradrenergic and specific serotonin antagonist

Activates 5-HT2, blocks 5-HT3.
Alpha 2 blockage at higher doses (which is why higher doses less sedating)

96
Q

What is the side effect profile of buproprion?

A

Similar to SSRIs, but rarely see sexual side effects

97
Q

What is the side effect profile of mirtazapine?

A

Appetite stimulation (weight gain) and, at low doses, sedation

98
Q

Why is mirtazapine sedating at low doses but not high doses?

A

At high doses, blocks alpha2 receptor, leading to increased NE release.

99
Q

In what types of patients is mirtazapine especially useful in?

A

Patients with poor appetite (stimulates appetite) and, at low doses, difficulty sleeping (sedating at low doses)

100
Q

What antidepressants can be used as adjuncts on top of SSRIs?

A

Buproprion (NDRI)

Buspirone

101
Q

What are the primary mood stabilizers?

A

Lithium and Valproate

102
Q

What are the common side effects of lithium?

A

Polydypsia/polyuria, sedation, tremor

103
Q

What are the dangerous side effects of lithium?

A

Renal impairment, nephrogenic DI, thyroid dysfunction

104
Q

What are signs of lithium levels being too high?

A

Coarse tremor, N/V/D, ataxia, AMS, renal failure, convulsions, coma

105
Q

What is the therapeutic window for lithium?

A

0.7 - 1.2

106
Q

What labs need to be followed in patients on lithium?

A

Lithium levels
BUN/Cr (for renal impairment)
T4/TSH (for thyroid dysfunction)

107
Q

What types of drugs have interactions with lithium?

A

Diuretics, NSAIDs

108
Q

What are common side effects of valproate?

A

Sedation, weight gain, alopecia

109
Q

What are dangerous side effects of valproate?

A

Thrombocytopenia, pancreatitis, hepatotoxicity

Also many drug interactions

110
Q

What labs need to be followed in patients on valproate?

A

Valpraote levels
Platelets (thrombocytopenia)
LFTs (hepatotoxicity, pancreatitis)

111
Q

What are signs of valproate toxicity?

A

Nystagmus, N/V, ataxia, lethargy, coma

112
Q

What psychiatric medication is associated with neural tube defects?

A

Valproate

113
Q

What are 3 secondary mood stabilizers?

A

Carbamazepine (Tegretol) / Oxcarbamazepine (Trileptal)
Lamotrigine (Lamictal)
Topiramate (Topamax)

114
Q

What secondary mood stabilizer has best evidence for use?

A

Carbamazepine (Tegretol) / Oxcarbamezepine (Trileptal)

115
Q

What are dangerous side effects of carbamazepine?

A

Bone marrow suppression, SIADH

Also many drug interactions

116
Q

In what patients is lithium CI in?

A

Renal disease

117
Q

What is the role of lamotrigine in bipolar disorder?

A

Used to prevent episodes, not useful during acute episode

118
Q

What are the dangerous side effects of lamotrigine?

A

SJS

119
Q

What secondary mood stabilizer does not actually have evidence for efficacy?

A

Topiramate (Topamax)

120
Q

What are the side effects of topiramate?

A

“Dopamax” (somnolence, depression, cognitive effects)

Kidney stones

121
Q

What can topiramate be used for?

A
  1. Secondary mood stabilizer (but not evidence for efficacy)
  2. Weight loss
  3. Headaches
  4. Impulse control in borderline PD

And, of course, epilepsy treatment.

122
Q

What benzodiazapene has relatively low potential for abuse?

What about its kinetics makes it useful for this?

A

Clonazepam (Klonipin)

Less potential for abuse due to slow kinetics

123
Q

What benzodiazapene is often used for alcohol withdrawal?

What about its kinetics makes it useful for this?

A

Chlordiazepoxide (Librium).

Very long effective half-life (active metabolize has half life of several days)

124
Q

What benzodiazepene is often used as a sleep aid?

What about its kinetics makes it useful for this?

A

Triazolam (Halcion)

Rapid onset, short half-life

125
Q

What benzodiazepene is highly addictive?

What about its kinetics contributes to this?

A

Alprazolam (Xanax)

Fast/intermediate onset, short/intermediate half-life

(Fastest kinetics other than triazolam, which puts patients to sleep)

(Fast onset also good for panic attacks)

126
Q

What benzodiazepene is often used for panic attacks?

What about its kinetics makes it useful for this?

A

Alprazolam (Xanax)

Fast/intermediate onset, short/intermediate half-life

(Fastest kinetics other than triazolam, which puts patients to sleep)

(Fast onset also makes it HIGHLY ADDICTIVE)

127
Q

What are the kinetics of lorazepam?

A

Intermediate onset of action and half-life

a.k.a. Ativan

128
Q

What are the kinetics of diazepam?

A

Fast onset, long half-life

a.k.a. Valium

129
Q

What are the kinetics of alprazolam?

A

Fast/intermediate onset, short/intermediate half-life

a.k.a. xanax

130
Q

What are the kinetics of clonazepam?

A

Slow onset, intermediate/long half-life

(Slow onset means less abuse potential)

(a.k.a. Klonopin)

131
Q

What hypnotic can lead to strange dreams and dissociative symptoms?

A

Zoldipem (Ambien)

132
Q

What hypnotic becomes less effective after two weeks use?

A

Zoldipem (Ambien)

133
Q

What hypnotic is very short-acting and may be taken if wake in the middle of the night?

A

Zapeplon (Sonata)

But can be habit forming as a result

134
Q

What hypnotic can be habit forming?

A

Zapeplon (Sonata)

Very short acting, may be taken if wake up in the middle of the night

135
Q

What hypnotic is similar to melatonin?

A

Remalteon (Rozerem)

Unlikely to be habit-forming

136
Q

What hypnotic can be taken for longer periods of time than others?

A

Eszopiclone (Lunesta)

But can lead to withdrawal syndrome

137
Q

What hypnotic can lead to a metallic taste in the mouth?

A

Eszopiclone (Lunesta)

138
Q

What hypnotic can lead to a withdrawal syndrome?

A

Eszopiclone (Lunesta)

But can be taken for longer periods than other hypnotics

139
Q

What hypnotic can lead to priapism?

A

Trazadone (Desyrel)

Relatively benign, commonly used on inpatient unit

140
Q

What hypnotic can lead to grogginess in the morning?

A

Trazadone (Desyrel)

Relatively benign other than rarely causing priapism, commonly used on inpatient unit

Psychiatry (9 decks)

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