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Neuropsychopharmacology Lecture and Handout COPY 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
How strongly do haloperisol, fluphenazine, perphenazine, and chlorpromazine each block D2, M1, H1, and alpha1 receptors?
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.
26
What are 4 typical antipsychotics?
Haloperidol (Haldol) Fluphenazine (Proloxin) Perphenazine (Trilafon) Chlorpromazine (Throazine)
27
Which antipsychotics have the highest incidence of EPS?
Typicals: haloperidol, fluphenazine Atypical: Risperidone
28
Which antipsychotics have long-acting forms?
``` Typicals: 1. Haloperidol deconoate 2. Fluphenzaine decanoate Atypicals: 1. Risperidone consta 2. Aripiprazole lauroxil ```
29
Which antipsychotics are most sedating?
Typical: Chlorpromazine (thorazine) Atypical: Quetiapine (seroquel)
30
Which typical antipsychotic(s) has the most anti-cholinergic side effects?
Chlorpromazine (thorazine)
31
What typical antipyschotic(s) has the least EPS?
Chlorpromazine (thorazine) - because of ACH block
32
What are the two hypotheses as to why atypical antipsychotics tend to have fewer EPS and more efficacy for negative symptoms?
Serotonin-dopamine antagonism theory: 5-HT2 receptor blockage "Fast off" theory: rapid dissociation from D2 receptors
33
What receptors are potentially involved in antipsychotic-related weight gain?
H1 and 5-HT2C blockage
34
What did the CATIE trial show about typical vs. atypical antipsychotics?
Perphenazine (Trilafon), the only typical studied, was as efficacious and well-tolerated as the atypicals
35
What atypical antipsychotic(s) is most associated with hyperprolactinemia?
Risperidone (Risperdal)
36
What are symptoms of hyperprolactinemia in women? Men?
Women: amenorrhea, galactorrhea Men: decreased libido (early sign), gynecomastia
37
What atypical antipsychotic(s) is most associated with metabolic syndrome?
Olanzapine (Zyprexa), Clozapine (Clozaril)
38
What atypical antipsychotic(s) is most associated with akathisia?
Aripiprazole (Abilify) | The atypical antipsychotic that is activating rather than sedating
39
What is the only antipsychotic also approved as an adjunct antidepressant?
Aripiprazole (Abilify)
40
Which atypical antipsychotic(s) is more weight neutral?
Aripiprazole (Abilify), Ziprasidone (Geodon)
41
What atypical antipsychotic(s) is more activating rather than sedating?
Aripiprazole (Abilify) | Can activate too much and lead to akathisia
42
What atypical antipsychotic is most associated with orthostatic hypotension?
Quetiapine (Seroquel)
43
What atypical antipsychotic(s) can be useful as a sleep aid?
Quetiapine (Seroquel) | Also approved as a mood stabilizer
44
What atypical antipsychic(s) is approved as a monotherapy mood stabilizer?
Quetiapine (Seroquel) | Also can be used as sleep aid
45
What atypical antipsychotic(s) may be useful in bipolar depression?
Quetiapine (Seroquel) | Also approved as monotherapy mood stabilizer
46
What atypical antipsychotic is by far the worse for QT prolongation?
Ziprasidone (Geodon) | Rarely used for this reason as well as needed to be taken with a meal
47
What atypical antipsychotic(s) is associated with drooling?
Clozapine (Clozaril)
48
What atypical antipsychotic(s) is associated with agranylocytosis?
Clozapine (Clozaril) | Effective but dangerous - also decreases seizure threshold
49
What atypical antipsychotic(s) significantly lowers the seizure threshold?
Clozapine (Clozaril) | Effective but dangerous - also leads to agranulocytosis
50
What monoamines are broken down by MAO-A? MAO-B?
MAO-A: Serotonin, melatonin, Epi, NE, DA. MAO-B: DA, phenylethylamine, trace amines (Note that DA is broken down by both)
51
What MAOI is selective for MAO-B? What is the implication of this?
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.
52
What are 4 common MAOIs?
Phenelzine (Nardil) Tranylcypromine (Parnate) Isocarboxazid (Marplan) Selegiline (MAO-B selective)
53
What are common side effects of MAOIs?
Orthostatic hypotension, sleep disturbence, GI distress, dry mouth, headache
54
What are the dangerous side effects of MAOIs?
``` Serotonin syndrome Hypertensive crisis (tyramine interaction) ```
55
What are symptoms of serotonin syndrome?
Flushing, diaphoresis, myoclonic jerks
56
Other than antidepressants, what are 4 serotonergic drugs that can contribute to serotonin syndrome?
1. Linezolid (antibiotic against resistant gram-positives) 2. Tramadol (opioid painkiller) 3. Miperidime (Demerol, opioid painkiller) 4. Dextromethorphan (cough suppressant opioid)
57
How is hypertensive crisis with MAOI tyramine interaction treated?
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
What type of antidepressant has significant dietary restrictions?
MAOIs (due to tyramine hypertensive crisis) | Tyramine in aged cheese, Chanti, fava beans, liver, cured meats, soy sauce, sauerkraut
59
What is the on-target pharmacologic actions of tricyclic antidepressants? Off-target?
On target: Inhibits NE and 5-HT reuptake | Off-ticked: Histamine, Muscarinic, Alpha-adrenergic blockade
60
What MAOI has amphetamine-like properties?
Tranylcypromine (Parnate)
61
What are common side-effects of TCAs?
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
What are dangerous side-effects of TCAs?
1. Cardiac conduction disruption, leads widened QRS, long QT, and arrhythmia) 2. Lethal in overdose
63
What drug effect is signified by widened QRS on EKG? How is this treated?
TCA overdose (also see long QT). Treatment: Sodium bicarbonate and magnesium
64
What TCA is approved for insomnia treatment?
Doxepin
65
What TCA is least likely to cause orthostatic hypotension?
Nortriptyline (Pamelor)
66
What TCA is least sedating?
Desipramine (Norpramin) | also fewest anticholinergic side effects
67
What TCA has the fewest anti-cholinergic side effects?
Desipramine (Norpramin) | also least sedating
68
What TCA is the most 5-HT specific?
Clomipramine (Anafranil) | Incidentally, also used in treating OCD
69
What TCA is also used in treating OCD?
Clomipramine (Anafranil) | Incidentally, also most 5-HT specific
70
Other than depression, what can TCAs be used to treat?
Chronic pain, headache. | Clomipramine (Anafranil) can be used for OCD as well
71
What are three TCAs?
Nortyrptyline (Pamelor) Desipramine (Norpramin) Clomipramine (Anafranil) Others: Imipramine, Amitryptyline, Doxepin
72
What SSRI has an extremely long half-life and therefore has no need to taper before stopping?
Fluoxetine (Prozac)
73
What SSRI is considered relatively activating?
Fluoxetine (Prozac) | Can worsen anxiety
74
What SSRI is considered relatively sedating?
Paroxetine (Paxil)
75
What is the "dirtiest" SSRI with the most side effects in general?
Fluoxetine (Prozac) | Sexual dysfunction is particularly bad
76
What SSRI is worst for sexual dysfunction?
Fluoxetine (Prozac)
77
What SSRI(s) can worsen anxiety?
Fluoxetine (Prozac) | Relativley activating
78
What SSRI(s) can be used in anxiety disorders?
Paroxetine (Paxil) | Sertraline (Zoloft)
79
What SSRI(s) has a short-life and therefore significant discontinuation syndrome with missed doses?
Paroxetine (Paxil) Sertraline (Zoloft) Fluvocamine (Luvox) - so short it requires BID dosing.
80
Compare and contrast Fluoxetine and Paxil in terms of: 1. Activation/sedation 2. Effect on anxiety 3. Half-life
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
What SSRI(s) have few drug-drug interactions?
Sertraline (Zoloft) Citalopram (Celexa) and Escitalopram (Lexapro) (Newer drugs)
82
What SSRI tends to cause more GI upset when starting?
Sertraline (Zoloft)
83
What SSRI has a very low incidence of common SSRI-related side effects?
Citalopram (Celexa) | Except can prolong QTc
84
What SSRI can lead to QT prolongation?
Citalopram (Celexa) | Otherwise few side effects
85
What are common side effects of SSRIs?
Sexual dysfunction, GI upset, headache.
86
What SSRI is actually not approved for depression? What is is approved for?
Fluvoxamine (Luvox) Approved for OCD and social anxiety disorder.
87
What are 4 SSRIs approved for depression?
Fluoxetine (Prozac) Paroxetine (Paxil) Sertraline (Zoloft) Citalopram (Celexa) / Escitalopram (Lexapro) (Fluvoxamine (Luvox) is not approved for depression, instead for OCD and social anxiety)
88
What are two SNRIs?
Venlafaxine (Effexor) | Duloxetine (Cymbalta)
89
What else can SNRIs potentially help with?
Chronic pain
90
In what patients is the SNRI contraindicated in?
Poorly controlled hypertension
91
What is the mechanism of action of buproprion?
NDRI: NE/DA reuptake inhibitor
92
How do side effects of SNRIs compare to SSRIs, in general?
Similar. May be more activating than most SSRIs.
93
What are the advantages of buproprion?
1. Rarely has sexual side effects 2. Can help stop smoking. 3. Relatively activating (but can worsen anxiety)
94
What are the disadvantages of buproprion?
1. Can worsen anxiety (relatively activating) 2. Lowers seizure threshold, CI in epilepsy 3. CI in eating disorder patients
95
What is the mechanism of action of mirtazapine?
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
What is the side effect profile of buproprion?
Similar to SSRIs, but rarely see sexual side effects
97
What is the side effect profile of mirtazapine?
Appetite stimulation (weight gain) and, at low doses, sedation
98
Why is mirtazapine sedating at low doses but not high doses?
At high doses, blocks alpha2 receptor, leading to increased NE release.
99
In what types of patients is mirtazapine especially useful in?
Patients with poor appetite (stimulates appetite) and, at low doses, difficulty sleeping (sedating at low doses)
100
What antidepressants can be used as adjuncts on top of SSRIs?
Buproprion (NDRI) | Buspirone
101
What are the primary mood stabilizers?
Lithium and Valproate
102
What are the common side effects of lithium?
Polydypsia/polyuria, sedation, tremor
103
What are the dangerous side effects of lithium?
Renal impairment, nephrogenic DI, thyroid dysfunction
104
What are signs of lithium levels being too high?
***Coarse tremor***, N/V/D, ataxia, AMS, renal failure, convulsions, coma
105
What is the therapeutic window for lithium?
0.7 - 1.2
106
What labs need to be followed in patients on lithium?
Lithium levels BUN/Cr (for renal impairment) T4/TSH (for thyroid dysfunction)
107
What types of drugs have interactions with lithium?
Diuretics, NSAIDs
108
What are common side effects of valproate?
Sedation, weight gain, alopecia
109
What are dangerous side effects of valproate?
Thrombocytopenia, pancreatitis, hepatotoxicity | Also many drug interactions
110
What labs need to be followed in patients on valproate?
Valpraote levels Platelets (thrombocytopenia) LFTs (hepatotoxicity, pancreatitis)
111
What are signs of valproate toxicity?
***Nystagmus***, N/V, ataxia, lethargy, coma
112
What psychiatric medication is associated with neural tube defects?
Valproate
113
What are 3 secondary mood stabilizers?
Carbamazepine (Tegretol) / Oxcarbamazepine (Trileptal) Lamotrigine (Lamictal) Topiramate (Topamax)
114
What secondary mood stabilizer has best evidence for use?
Carbamazepine (Tegretol) / Oxcarbamezepine (Trileptal)
115
What are dangerous side effects of carbamazepine?
Bone marrow suppression, SIADH Also many drug interactions
116
In what patients is lithium CI in?
Renal disease
117
What is the role of lamotrigine in bipolar disorder?
Used to prevent episodes, not useful during acute episode
118
What are the dangerous side effects of lamotrigine?
SJS
119
What secondary mood stabilizer does not actually have evidence for efficacy?
Topiramate (Topamax)
120
What are the side effects of topiramate?
"Dopamax" (somnolence, depression, cognitive effects) | Kidney stones
121
What can topiramate be used for?
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
What benzodiazapene has relatively low potential for abuse? What about its kinetics makes it useful for this?
Clonazepam (Klonipin) Less potential for abuse due to slow kinetics
123
What benzodiazapene is often used for alcohol withdrawal? What about its kinetics makes it useful for this?
Chlordiazepoxide (Librium). Very long effective half-life (active metabolize has half life of several days)
124
What benzodiazepene is often used as a sleep aid? What about its kinetics makes it useful for this?
Triazolam (Halcion) Rapid onset, short half-life
125
What benzodiazepene is highly addictive? What about its kinetics contributes to this?
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
What benzodiazepene is often used for panic attacks? What about its kinetics makes it useful for this?
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
What are the kinetics of lorazepam?
Intermediate onset of action and half-life | a.k.a. Ativan
128
What are the kinetics of diazepam?
Fast onset, long half-life | a.k.a. Valium
129
What are the kinetics of alprazolam?
Fast/intermediate onset, short/intermediate half-life | a.k.a. xanax
130
What are the kinetics of clonazepam?
Slow onset, intermediate/long half-life (Slow onset means less abuse potential) (a.k.a. Klonopin)
131
What hypnotic can lead to strange dreams and dissociative symptoms?
Zoldipem (Ambien)
132
What hypnotic becomes less effective after two weeks use?
Zoldipem (Ambien)
133
What hypnotic is very short-acting and may be taken if wake in the middle of the night?
Zapeplon (Sonata) | But can be habit forming as a result
134
What hypnotic can be habit forming?
Zapeplon (Sonata) | Very short acting, may be taken if wake up in the middle of the night
135
What hypnotic is similar to melatonin?
Remalteon (Rozerem) Unlikely to be habit-forming
136
What hypnotic can be taken for longer periods of time than others?
Eszopiclone (Lunesta) | But can lead to withdrawal syndrome
137
What hypnotic can lead to a metallic taste in the mouth?
Eszopiclone (Lunesta)
138
What hypnotic can lead to a withdrawal syndrome?
Eszopiclone (Lunesta) | But can be taken for longer periods than other hypnotics
139
What hypnotic can lead to priapism?
Trazadone (Desyrel) | Relatively benign, commonly used on inpatient unit
140
What hypnotic can lead to grogginess in the morning?
Trazadone (Desyrel) | Relatively benign other than rarely causing priapism, commonly used on inpatient unit

Psychiatry (9 decks)

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