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Psych Exam 1 > Antipsychotics (Linger) - SRS > Flashcards

Antipsychotics (Linger) - SRS Flashcards

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1
Q

What are the atypical (second generation) antipsychotics?

11 with 8 bold. Good times

A
  1. Aripiprazole (Abilify)
  2. Brexpiprazole (Rexulti)
  3. Cariprazine (Vraylar)
  4. Lurasidone (Latuda)
  5. Olanzapine (Zyprexa)
  6. Quetiapine (Seroquel)
  7. Risperidone (Risperdal)
  8. Ziprasidone (Geodon)
  9. Asenapine (Saphris)
  10. Iloperidone (Fanapt)
  11. Paliperidone (Invega)
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2
Q

What is the one (bold) special use atypical antipsychotic?

A
  1. Clozapine (Clozaril)
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3
Q

What are the two typical (first-generation) low potency agents? one bold

A
  1. Chlorpromazine (Thorazine)
  2. Thioridazine (Mellaril)
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4
Q

What are the typical (first-generation) high-potency agents?

A
  1. Haloperidol (Haldol)
    1. Haldol decanoate (depot)
  2. Fluphenazine (Prolixin)
    1. Fluphenazine decanoate (depot)
  3. Loxapine (Loxitane)
  4. Perphenazine
  5. Pimozide (Orap)
  6. Thiothixene (Navane)
  7. Trifluoperazine
  8. Molindone (Moban)
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5
Q

Why are the atypical antipsychotics referred to as such?

A

d/t the dramatic reduction in EPS at clinically effective doses

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6
Q

What are the three hypotheses for the biological basis of schizophrenia?

A
  1. Dopamine hypothesis
  2. serotonin hypothesis
  3. Glutamate hypothesis
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7
Q

What are the major chemical classes used for antipsychosis?

A
  1. Phenothiazine derivatives
  2. thioxanthene derivatives
  3. butyrophenone derivatives
  4. miscellaneous
  5. atypical antipsychotics
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8
Q

For the most part discontinuation of antipsychotics is well tolerated. With what three noteable exceptions?

How do these exceptions manifest their withdrawal symptoms?

A

Clozapine

  • cholinergic rebound
  • withdrawal-emergent movement disorders

Chlopromazine

  • cholinergic rebound

Thioridazine

  • cholinergic rebound
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9
Q

Time to relapse in stable schizophrenics who discontinue meds is highly variable with an average of what time to relapse?

What is an exception to this generalization?

A

6 months

Clozapine

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10
Q

What enzyme is responsible for the degredation of most antipsychotics?

A

CYP450

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11
Q

Efficacy of the typical antipsychotics is primarily driven by?

A

D2 receptor blockade

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12
Q

What are the two pathways and one system that are impacted by antipsychotics?

A
  1. Mesolimbic-mesocortical pathway
  2. nigrostriatal pathway
  3. tuberoinfundibular system
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13
Q

What is the mesolimbic-mesocortical pathway involved in?

A

involved in behavior and cognitive function

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14
Q

What structures are involved in the mesolimbic-mesocortical pathway?

A

Cell bodies in the ventral tegmentum send projections to the limbic system and neocortex

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15
Q

What the hell does the tuberoinfundibular system do?

A

regulates prolactin release via the arcuate nucleus and periventricular neurons that project to the hypothalamus and posterior pituitary.

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16
Q

Given that the tuberoinfundibular system is impacted by antipsychotics, what would you expect to be a possible ADR associated with the older antipsychotics to be?

A

Hyperprolactinemia

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17
Q

What are the dopamine receptor subtypes that have been cloned and studied to date?

A

D1, D2, D3, D4, D5

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18
Q

Describe the mechanisms of action for the various dopamine receptors.

A

D1 and D5 - Gs

increase camp via activation of Gs coupled adenylyl cyclase

D2, D3, D4 - Gi

decrease camp via inhibition of Calcium channels, opening potassium channels.

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19
Q

Where are the D1 and D5 receptors primarily found?

A
  1. nucleus accumbens
  2. putamen
  3. olfactory tubercle
  4. cortex
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20
Q

Where are the D2,3,4 receptors mostly found?

A

both pre and post synaptically in the

  1. caudate-putamen
  2. nucleus accumbens
  3. olfactory tubercle
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21
Q

What are the only dopamine receptors shown to play a role in the action of antipsychotics?

A

D2

(D1,3,4 have been extensively tested with zero evidence of efficacy in treatment of psychosis)

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22
Q

D2 binding is very strongly associated with antipsychotic potency and what type of toxicity?

A

extrapyramidal

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23
Q

What percent of D2 receptors must be bound before antipsychotic efficacy can be achieved?

When EPS produced?

A
  • 60%
  • at 80% or greater for EPS
24
Q

At what receptor occcupancy level do the atypical antipsychotic drugs produce efficacy?

A

At 30-50%

25
Q

What drug exhibits high D2 occupancy without EPS?

Why?

A

Aripiprazole - is a partial agonist at D2 and also is a 5-ht2a antagonist and 5-ht1A partial agonism

26
Q

What drugs are best used to manage catatonic forms of schizophrenia?

A

IV benzodiazepines

27
Q

What are the antipsychotics primarily used to treat?

A

schizophrenia (acute control and maintenance)

28
Q

What are some other conditions treatable with antipsychotics?

A
  1. psychotic depression
  2. acute mania
  3. bipolar disorder
  4. schozoaffective disorders
  5. behavioral disturbances in dementia
  6. behavioral disturbances in children and teens
  7. Tourette’s
  8. AD
  9. drug-induced psychosis
  10. refractory depression
29
Q

What drug has been shown in random trials to reduce suicide attempts in patients with schizoaffective disorder who are at high risk for attempts?

A

Clozapine

30
Q

What are some non-psychiatric indications for antipsychotic drugs?

A
  1. antiemesis - e.g. metaclopramide and others
  2. neuroleptanesthesia - droperidol (a butyrophenone D2 blocker) + fentanyl + nitrous oxide)
31
Q

Atypical antipsychotics are now considered first-line tx for schozophrenia and other mental disorders with psychotic features. What are two exceptions to this?

A

Clozapine

olanzapine

32
Q

What is the major advantage of the atypical antipsychotics?

A

less likely to cause extrapyramidal symptoms and tardive dyskenisia

33
Q

What formulation is the best dosing strategy for both acute and long term controll of uncooperative patients?

A

Intramuscular

34
Q

Generally is the therapeutic index wide or narrow for the antipsychotics?

A

Wide

35
Q

If a patient fails on one antipsychotic, will they likely fail on other drugs?

A

No, high degree of variable responses to different drugs.

36
Q
  1. Broadly, all the antipsychotics, except clozapine and olanzapine, are considered equally effective for reducing psychosis; 30-50% of patients refractory to standard doses of other antipsychotics respond to what options?
A
  1. clozapine
  2. high-dose olanzapine
37
Q

Why is it that clozapine is generally reserved for use with patients who have become refractory to high doses of other agents or who have attempted suicide?

A

Serious ADRs including agranulocytosis and myocarditis

38
Q

How rapidly can psychotic symptoms improve?

How long is generally required before full effect?

How long may maintenance therapy continue?

A
  • 1 week
  • 16-20 weeks
  • a lifetime
39
Q

What is generally the best approach to treating psychotic disorders, monotherapy or poly?

A

Polypharmacy - difficult to control all symptoms with one medication alone.

40
Q

What are the behavioral ADRs associated with the older antipsychotics?

A
  • anhedonia
  • akinesia
  • toxic-confusional states
  • sedation
41
Q

Antipsychotics have both early and late motor effects. What are the early ones?

A
  1. pseudo-Parkinsonism
  2. akathisia (uncotrollable restlessness)
  3. acute dystonic reactions
  4. EPS
42
Q

What can be used to treat the EPS and dystonic reactions?

A

anticholinergic such as benztropine

or

antihistamine that also hits muscarine receptors

43
Q

What drug should never be used to control the motor effects of antipsychotics?

A

Levodopa

44
Q

What are the late motor effects of the antipsychotics?

A

Tardive diskenesia

45
Q

What is the rate of tardive dyskenisia in the older, typical antipsychotics?

A

20-40%

46
Q

If a patient begins exhibiting signs of tardive diskenesia, what should be done?

A

Switch them to either quetiapine or clozapine - drugs with the lowest risk of tardive dyskinesia.

47
Q

Apart from the early and late motor ADRs, what is another neurological ADR associated with the antipsychotic drugs?

A

decreased seizure threshold

48
Q

Can most antipsychotics be used in epileptics?

A

Yes.

49
Q

What ANS ADRs are seen in the older antipsychotics?

A

Anticholinergic effects: dry mouth, loss of accomodation, urinary retention, constipation, impotence

Alpha-adrenergic effects: orthostatic hypotension, dissiness, sedation, failure to ejaculate.

50
Q

What are the metabolic and endocrine ADRs associated with antipsychotics?

A
  1. Weight gain
  2. hyperprolactinemia
51
Q

Antipsychotics can be characterized as being high risk, intermediate risk, low risk and lowest risk for causing weight gain.

What are the drugs associated with each risk level?

A
  • Highest risk for weight gain: Clozapine, Olanzapine
  • Intermediate risk: Iloperidone, Paliperidone, Quetiapine, Risperidone
  • Low risk: Asenapine
  • Lowest risk: Aripiprazole, Lurasidone, Ziprasidone
52
Q

What lab testing must be done every week for the first 6 months of tx and every 3 weeks after when using clozapine?

A

Blood counts - to check for agranulocytosis

53
Q

What cardiac ADRs are associated with the antipsychotics?

A

Long QT with increased risk of Sudden death

54
Q

During pregnancy should the typicals or atypicals be used to treat the patient?

A

Atypicals are best and considered relatively safe. Most are category C

55
Q

Neuroleptic Malignant syndrome occurs in patients who are extremely sensitive to EPS. What are the components of this?

6

A

Rare but life threatening and include…

  1. acute severe parkinsonism
  2. muscle rigidity
  3. autonomic instability
  4. hypertension
  5. hyperthermia
  6. stress leukocytosis
56
Q

Overdosing on antipsychotics is rarely fatal, with what exception?

A

Thioridazine - causes arrhythmias

Psych Exam 1 (6 decks)

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