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Antipsychotics Flashcards

1
Q

Lithium MOA

(we don’t actually know, but what is the hypothesis)

A

Depletes inositol → stops signal transduction → decreases hyperexcitatory state → decreases mania (will do NOTHING to a healthy person)

(3 strategies: block recycling, stop transporter, increase CREB to increase BDNF & Bcl-2)

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2
Q

Lithium facilitates ______ neurotransmission & inhibits ______ excitatory neurotransmission

A
  • inhibitory (GABA)
  • excitatory (Glu & DA)
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3
Q

Neuromuscular adverse effects of lithium (3)

A
  1. Tremor
  2. Muscle hyperirritability ataxia
  3. Extrapyramidal symptoms
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4
Q

Lithium cardiac adverse effects (3)

A
  1. Arrhythmia
  2. Hypotension
  3. Peripheral circulatory collapse
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5
Q

Lithium effect on chronic kidney disease: symptoms

A

Nephrogenic diabetes insipidus (including polyuria, thirst and polydipsia)

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6
Q

Lithium may cause ________ (metallic or salty taste).

A

dysgeusia/taste distortion

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7
Q

Lithium may cause which thyroid abnormalities?

A
  • Euthyroid goiter and/or hypothyroidism (including myxedema)
  • Lower T3 & T4
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8
Q

______ is used in patients with low leukocyte counts.

A

lithium

(it will always be present during lithium treatment, so it is used off-label for this purpose)

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9
Q

Lithium is primarily excreted by _______.

A

kidneys

(proportionately to serum concentration; 80% reabsorbed via passive diffusion)

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10
Q

Haloperidol and lithium may cause ______

A

Encephalopathic syndrome

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11
Q

Lithium may prolong the effects of _______ agents

A

neuromuscular blocking

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12
Q

Lithium and diuretics or angiotensin-converting enzyme inhibitors may decrease _____

A

clearance of lithium

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13
Q

Atypical antipsychotics may produce more severe ________ (AE) when combined with lithium.

(exeption: Clozapine)

A

extrapyramidal syndrome

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14
Q

Lithium contraindications (3)

A
  1. renal disease
  2. cardiovascular disease
  3. Bradycardia - tachycardia syndrome (“sick sinus”)
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15
Q

Therapeutic overdoses are usually due to the accumulation of lithium. This is usually caused by changes to the patient’s status such as _______ (3).

A
  1. Diminished serum sodium
  2. Use of diuretics
  3. Fluctuating renal function
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16
Q

A value of over of _____ serum concentration is considered lithium toxicity.

A

2 mEq/L

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17
Q

Which type of dialysis is preferred for treating lithium toxicity / overdose?

A

Hemodialysis

(peritoneal dialysis may also be used)

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18
Q

In addition to treating bipolar (mainenance & mania) and cyclic depression, lithium may be used as _______ adjunct therapy.

A

unipolar depression

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19
Q

List 4 mood stabilitzers that treat acute mania and/or bipolar maintenane

A
  1. Lithium
  2. Valproate
  3. Carbamazepine
  4. Lamotrigine
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20
Q

Schizophrenia is typically diagnosed in which age group?

A
  • Females: Early 20s to early 30s
  • Males: Late adolescence to early 20s

(in general, late teens to early thirties : this is the age where ppl start to use their pre-frontal cortex more and symptoms start to appear)

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21
Q

What are the three categories of schizophrenic symptoms?

A
  1. Positive
  2. Negative
  3. Cognitive
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22
Q

Positive symptoms of schizophrenia are psychotic behavior is not seen in _____

A

Healthy people

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23
Q

Schizophrenia: positive symptoms observed in patient

A
  1. Altered perceptions
  2. Abnormal thinking
  3. Odd behaviors
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24
Q

Schizophrenia: positive symptoms the individual experiences

A
  1. Hallucinations
  2. Delusions
  3. Thought disorder (unusual thinking & disorganized speech)
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25
Q

Mesocortical pathway is associated with _______ symptoms of schizophrenia.

A

negative

(DA influences preception, cognition & social behavior)

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26
Q

Altered Perceptions in schizophrenia: they experience changes in _____ (5)

A
  1. Vision
  2. Hearing
  3. Smell
  4. Taste
  5. Touch
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27
Q

Example of delusions experienced by schizophrenic patients (positive symptoms) (2)

A
  1. Paranoia or irrational fears that others are “ out to get you”
  2. Believing that the television, radio or Internet are broadcasting special messages that require your response
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28
Q

Negative symptoms of schizophrenia: (5)

A
  1. Loss of motivation
  2. Disinterest or lack of enjoyment in daily activities
  3. Social withdrawal
  4. Flat affect
  5. Reduced speech
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29
Q

Cognitive symptoms of schizophrenia include problems with _____ (3).

A
  1. Attention
  2. Concentration
  3. Memory
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30
Q

Cognitive symptoms of schizophrenia: patients typically experiences difficulties with ______ (3)

A
  1. Processing information to make decisions
  2. Using information immediately after learning it
  3. Focusing and paying attention
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31
Q

_______ (5) are commonly seen in patients with schizophrenia and can exacerbate the symptoms of their disorder.

A
  1. Anxiety
  2. Depression
  3. Panic
  4. OCD
  5. Substance abuse (EtOH, tobacco, prescription meds)
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32
Q

Schizophrenia: goals of treatment are to decrease dopamine in the _________ pathway and increase DA in the _____pathway, simultaneously.

A
  1. mesolimbic
  2. mesocortical

(we do NOT want to block nigrostriatal or tuberoinfundibular DA pathways)

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33
Q

While treating schizophrenia, the goal is to decrease DA in the mesolimbic & increase DA mesocortical pathways and NOT the _____ (2) pathways.

A
  1. Nigrostriatal
  2. Tuberoinfundibular
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34
Q

First generation antipsychotics are antagonists at which receptors (5)?

(classes are phenothiazines & non-phenothiazines)

A
  1. D2
  2. M1
  3. H1
  4. alpha 1
  5. alpha 2
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35
Q

Second generation antipsychotics are antagonist of which receptors?

A

5-HT2A / D2 antagonist / partial agonist (Inverse agonist)

(examples: Paliperidone, Risperidone, Pimavanserin)

36
Q

Disadvantages of Chlorpromazine

A

many adverse effects (especially autonomic)

(class: phenothiazine)

37
Q

Disadvantages of Olanzapine (2)

A
  1. Weight gain
  2. Dose-related lowering of seizure threshold

(class: Thienobenzodiazepine)

38
Q

Disadvantage of Ziprasidone

A

QT Prolongation

(class: dihydroindolone)

39
Q

What are the excitatory NTs in the brain?

A
  1. Glu
  2. DA

(lithium blocks these and increases GABA)

40
Q

Mesolimbic pathway is associated with _______ (2) symptoms of schizophrenia.

A

delusions and hallucinations

41
Q

Substance abuse disorder is commonly seen in schizophrenic patients. Why?

A

DA receptors are unavailable. They self-medicate to feel good.

(EtOH, smoking, prescription meds)

42
Q

Why is dosage titration important?

A

If you get over 85% receptor-binding, side effects will begin to show up

43
Q

Chlorpromazine Adverse Effects (8)

A
  1. Sedation
  2. Anticholinergic effects
  3. Orthostatic hypotension
  4. QT prolongation
  5. Deposits in cornea & lens of eye
  6. Photosensitivity
  7. Hyperglycemia
  8. Weight gain

(Others: SLE cells, False positive pregnancy tests,Tardive dyskinesia)

44
Q

Adverse effects of fluphenazine (5)

A
  1. Akathisia
  2. Parkinsoniaism
  3. Dystonia
  4. Tardive dyskinesia
  5. Prolactin elevation
45
Q

Haloperidol adverse effects: akathisia, parkinsonism, ______ (5)

A
  1. EPS: Dystonia, Tardive dyskinesia
  2. Hyperprolactinemia
  3. Face edema
  4. QT prolongation
  5. Photosensitivity, hyperhidrosis

(same as Fluphenazine + QT prolongation)

46
Q

Thioridazine adverse effects (5)

A
  1. Sedation
  2. Anticholinergic effects
  3. Orthostatic hypotension
  4. Retinitis pigmentosa (dose-dependent)
  5. Ventricular arrythmias
47
Q

Thiothixene adverse effects (5)

A
  1. EPS: Akathisia, Parkinsonism, Dystonia, Tardive dyskinesia
  2. Elevated prolactin levels

(as fluphenazine and haloperidol)

48
Q

Pimozide adverse effects (4)

A
  1. Akathisia
  2. Parkinsonism
  3. Tardive dyskinesia
  4. Prolactin elevation
49
Q

Blockade of D2 receptors in the mesolimbic pathway helps to reduce positive symptoms of schizophrenia but also shut down the reward pathway leaving patients with the following symptoms (3).

A
  1. Apathy
  2. Anhedonia
  3. Lacking motivation, interest and joy from social interactions

(similar to the negative symptoms of schizophrenia)

50
Q

Neuroleptic - induced deficiency syndrome

A

Blocking D2 receptors in the music cortical pathway can worsen negative and cognitive symptoms (even tho low density of D2 receptors in the cortex)

51
Q

Prolactin elevation from blocking D2 receptors in the tuberoinfundibular may lead to ______ (symptoms).

A
  1. Hyperprolactinemia → galactorrhea and am in area
  2. Fertility issues in women → rapid demineralization of bone in postmenopausal women, sexual dysfunction and weight gain
52
Q

Tardive dyskinesia treatment (2)

A
  1. Valbenazine
  2. Deutetrabenazine
53
Q

Chlormromazine indications (4)

A
  1. schizo, mania, bipolar
  2. childhood schizo & autism
  3. N/V in terminal illness
  4. Intractable hiccup
54
Q

Chlorpromazine is used as an adjunct therapy for _____ (2)

A
  1. short-term management of anxiety psychomotor agitation excitement
  2. violent or dangerously impuslive behavior
55
Q

Pharmacokinetics of ______ are complex; serum levels of unchanged drug and clinical effect do not correlate well.

A

Chlorpromazine

56
Q

Clozapine also causes granulocytopenia or agranulocytosis in approximately 1% of patients requiring _____.

A

regular blood cell count monitoring

57
Q

Clozapine is associated with excess risk of myocarditis and venous thromboembolic events including fatal pulmonary embolism. What are the other adverse affects (7)?

A
  1. sedation
  2. dizziness/vertigo
  3. HA
  4. tremor
  5. hypersalivation, dry mouth
  6. sweating
  7. visual disturbances
58
Q

______ (second gen. antipsychotic) carries the greatest risk of QT prolongation

A

Ziprasidone

59
Q

Quetiapine: prominent adverse effects (2)

A
  1. Sedation
  2. Hyperlipidemia
60
Q

Olanzapine prominent adverse effects: Weight gain, Glucose abnormalities, Hyperlipidemia, Hyperglycemia & diabetes mellitus, _______ (5).

A
  1. NMS
  2. Sedation
  3. Extremity pain
  4. Dry mouth
  5. Orthostatic hypotension
61
Q

In addition to weight gain glucose abnormalities and hyperlipidemia, what are three other prominent adverse effects of Clozapine?

A

Sedation
Orthostatic hypotension

62
Q

Why do a typical antipsychotics help with EPS symptoms?

A

blocks 5HT2A receptor → increases DA release

63
Q

5-HT2A antagonism → increase DA neurotransmission in the Nigrostriatal pathway, reducingEPS. 5-HT1A partial agonism helps increase DA release in ____ and inhibit _____ release.

A
  • PFC
  • glutamate

(Hyperpolarization of cortical pyramidal cells produce anxiolytic effects. Improve negative and cognitive symptoms by increasing dopamine release in the prefrontal cortex)

64
Q

Why do Clozapine and Quetiapine lower the risk of EPS?

A

They bind a more loosely to the D2 receptors

65
Q

Clozapine is a substrate for which enzymes?

A
  • CYP1A2
  • CYP3A4
66
Q

Olanzapine IM agitation is associated with ________ (2).

A
  1. schizophrenia
  2. bipolar I mania
67
Q

Which second generation antipsychotics are D2 & 5HT2A antagonists?

A
  1. Lurasidone
  2. Olanzapine
  3. Clozapine
68
Q

Laruasidone (Latuda) indications

A
  • Schizophrenia
  • Depressive episodes associated with Bipolar I Disorder (bipolar depression) (as monotherapy and as adjunctive therapy with lithium or valproate)
69
Q

Lurasidone (Latuda) metabolism mainly by _____ (enzyme).

A

CYP3A4.

(Grapefruit should be avoided, dose adjustment is needed in renal & hepatic impairment)

70
Q

Cariprazine indications

A
  • Schizophrenia
  • Acute treatment of manic or mixed episodes associated with bipolar I disorder

(same as Lurasidone/Latuda)

71
Q

Cariprazine AE (2)

A
  1. EPS: akathisia
  2. dyspepsia
  3. Pregnancy: EPS and/or withrawal sx in neonates w/3rd trimester exposure
72
Q

Cariprazine is metabolized extensively by ______ (enzyme) and weakly inhibits ______.

A
  • CYP3A4
  • CYP1A2, CYP2C9, CYP2D6, CYP3A4, CYP2C19, CYP2A6, and CYP2E1
73
Q

Cariprazine MOA

A
  • Partial agonist at the D3, D2 and 5-HT1A receptors
  • Antagonist at 5-HT2B and 5-HT2A receptors

(no appreciable affinity for muscarinic receptors)

74
Q

Which second generation antipsychotics are Partial agonist : 5-HT1A and D2 & Antagonist: 5-HT2A receptors

A
  1. Brexpiprazole
  2. Aripiprazole
75
Q

Brexpiprazole AE

A
  1. Suicide (<24 y.o.)
  2. Weight gain
  3. Akathisia
  4. Pathological gambling and other compulsive behaviors
76
Q

Asenapine Indications:

A
  • Schizophrenia
  • Bipolar I disorder (Acute monotherapy of manic or mixed episodes, in adults and pediatric patients 10 to 17 years of age. Maintenance monotherapy treatment in adults)
77
Q

Asenapine MOA

A

D2 and 5-HT2A receptor antagonist

78
Q

Asenapine is metbolized via glucuronidation by _____ and oxidative metabolism by _____.

A
  • UGT1A4
  • CYP1A2

(weak inhibitor of CYP2D6)

79
Q

Asenapine AE (3)

A
  1. Seizure
  2. Cognitive and motor impairment
  3. QT prolongation
80
Q

Aripiprazole (3rd gen. antipsychotic) Indications (6)

A
  1. Schizophrenia
  2. Agitation associated with schizophrenia or bipolar mania (Injection)
  3. Acute treatment of manic and mixed episodes associated with Bipolar I
  4. Adjunctive treatment of MDD
  5. Irritability assoc. w/Autistic disorder
  6. Tourette’s disorder
81
Q

Aripiprazole & Brexpiprazole are BOTH metabolized by ______ & _____.

A

CYP3A4 and CYP2D6

(Dosage adjustments are recommended in patients who are known CYP2D6 poor metabolizers and in patients taking concomitant CYP3A4 inhibitors or CYP2D6 inhibitors or strong CYP3A4 inducers)

82
Q

Aripiprazole AE: Hyperglycemia, Dyslipidemia, DM, Weight gain, ______(4).

A
  1. Seizure
  2. Cognitive & motor impairment
  3. NMS
  4. Tardive dyskinesia
83
Q

Neuroleptic Malignant Syndrome, aka _______, may be caused by almost any antipsychotic or tranquilizer (neuroleptic).

A
  1. Drug-Induced Movement Disorder
  2. Hyperthermia
  3. Neuroleptic-Induced acute dystonia
84
Q

Neuroleptic Malignant syndrom is caused by ______ antagonism

A

D2 receptor

85
Q

Neuroleptic Malignant Syndrome symptoms

A
  1. Fever (102 to 104 degrees F)
  2. Irregular pulse
  3. Tachycardia
  4. Tachypnea
  5. Muscle rigidity
  6. Altered mental status
  7. Autonomic nervous system dysfunction resulting in high or low blood pressure, profuse perspiration
  8. Other symptoms may include liver or kidney failure, hyperkalemia, rhabdomyolysis or blood clots in veins and arteries
86
Q

Neuroleptic Malignant Syndrome Tx (3)

A
  1. Diazepam
  2. Dantrolene
  3. Bromocriptine
87
Q

Why do antipsychotics also work for depression and other disorders

A

it has to do with the affinity for many receptors; at certain dosages it will have different effects (antidepression, sedation, etc)

Behavioral Medicine (35 decks)

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