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itx ii > Antipsychotics/EPS treatment > Flashcards

Antipsychotics/EPS treatment Flashcards

pharmacology/Medicinal Chemistry

1
Q

Butyrophenones

A

-Droperidol
-Haloperidol

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1
Q

First Generation

A

Typical antipsychotics
-Butyrophenones
-Diphenylbutylpiperidine
-Phenothiazines

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2
Q

Diphenylbutylpiperidine

A

-fluspirilene
-penfluridol
-pimozide

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3
Q

Phenothiazines

A

Chlorpromazine
fluphenazine
thioridazine

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4
Q

Second Generation

A

Atypical antipsychotics

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5
Q

Atypical antipsychotics

A

aripiprazole, clozapine, risperidone, brexpiprazole, cariprazine, pimavanserin, latuda

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6
Q

What are the four main properties of second gen. antipsychotics?

A
  1. less/fewer EPS
  2. less prolactinemia
  3. moa involves D2 blockade as well as 5-HT2 blockade
  4. more efficacy for neg. sx
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7
Q

All antipsychotics are antagonists for which receptor?

A

Dopamine D2 receptors

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8
Q

Clozapine blocks which Dopamine receptor?

A

D4

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9
Q

At what percentage occupancy of D2-receptors is needed for therapeutic effect

A

80%

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10
Q

What rare and serious idiosyncratic reaction do some antipsychotics cause?

A

agranulocytosis

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11
Q

What is a common side effect of Clozapine that causes routine monitoring?

A

Leukopenia

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12
Q

D2 receptor blockade causes…

A

EPS and movement disorder, sexual dysfunction, endocrine SE (prolactin elevation)

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13
Q

5-HT1 receptor blockade causes…

A

ejaculatory disturbances

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14
Q

5-HT2 receptor blockade causes…

A

hypotension, wt gain, reduced sexual dysfunction, insomnia

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15
Q

blockade of AcH receptor causes…

A

blurred vision, dry mouth, sinus tachycardia, constipation, urinary retention, memory difficulties, anti-EPS side effects

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16
Q

H1 receptor blockade causes…

A

sedation, wt gain, anti-EPS side effects

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17
Q

alpha-1 adrenergic receptor blockade causes…

A

orthostatic hypotension, dizziness, syncope, reflex tachycardia, sedation, priapism

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18
Q

Chlorpromazine

A
  • dopamine antagonist
    -low potency
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19
Q

Chlorpromazine is used to treat what diagnoses?

A

acute and chronic psychoses including schizophrenia and manic phase of bipolar disorder, amphetamine-induced psychoses

20
Q

chlorpromazine VERY COMMON adverse effects

A

sedation, somnolence eps, wt. gain, orthostatic hypotension, dry mouth, constipation

21
Q

Chlorpromazine COMMON adverse effects

A

ecg changes, contact dermatitis, photosensitivity, urticaria, maculopapular, petechial or edematous reactions, hyperprolactinaemia, impaired thermoregulation, hyperglycemia, etc.

22
Q

Chlorpromazine UNCOMMON adverse effects

A

miosis, urinary retention, nasal congestion, nausea, obstipation, arrhythmias, skin pigmentation, etc.

23
Q

Chlorpromazine RARE adverse effects

A

agranulocytosis, hemolytic anemia, aplastic anemia

24
Q

UNKNOWN FREQUENCY adverse effects of Chlorpromazine

A

leucopenia, eosinophilia, pancytopenia

25
Q

Haloperidol

A
  • an inverse agonist of dopamine
  • high potency antipsychotic
26
Q

Haloperidol can be used to treat what diagnoses?

A
  • treatment of acute psychosis, severe behavior disorders
27
Q

Haloperidol COMMON adverse effects

A

EPS, dystonia, muscle rigidity, akathisia, Parkinsonism, hypotension, constipation, dry mouth, blurred vision and somnolence

28
Q

Haloperidol RARE adverse effects

A

jaundice, hepatitis, cholestasis, acute hepatic failure, hyperglycemia, anaphylactic reaction, hypersensitivity, agranulocytosis, etc.

29
Q

Haloperidol UNKNOWN FREQUENCY adverse effects

A

prolonged Qt interval, orthostatic hypotension, increased respiratory rate, anemia, visual disturbances, HA, etc.

30
Q

Haloperidol Limitations

A

-1/2 pts of schizophrenia fails to respons
-limited efficacy against 1) neg. sx, 2) affective sx, 3) cognitive deficits
-high proportion of patients relapse
-SE and compliance issues
-some safety issues are prominent

31
Q

Atypical antipsychotics

A
  • MARTA
  • SDA
  • Selective D2/D3 antagonists
  • D2/D3 agonists
32
Q

MARTA (multi-acting receptor targeted agents)

A
  • clozapine
  • olanzapine
  • quietiapine
33
Q

SDA (serotonin-dopamine antagonists)

A

risperidone, ziprasidone

34
Q

Selective D2/D2 antagonists

A

aripiprazole

35
Q

D2/D3 partial agonists

A

Brexpiprazole (Rexulti)
Cariprazine (Vraylar)

36
Q

Clozapine

A

selectively blocks D2 receptors
more strongly blocks 5-HT receptors in cortex which then acts to modulate some dopamine active

37
Q

Clozapine adverse effects

A
  • orthostatic hypotension effects, sedation, wt. gain, increased HR
  • increased risk for seizures (2-3%)
  • agranulocytosis in 1%
  • Agranulocytosis risks increase when co-administered with carbamazepine
  • itxns with SSRIs and valproic acid increase clozapine levels and risks
38
Q

Ziprasidone

A
  • 5th atypical antipsychotic
  • antagonist/inverse agonist of 5-HT. dopamine receptor, adrenergic receptor, mACh receptor, and NE transporter
39
Q

Ziprasidone is used to treat what?

A

schizophrenia, acute mania and mixed states associated with bipolar disorder

40
Q

Ziprasidone VERY COMMON adverse effects

A

somnolence, HA

41
Q

Ziprasidone COMMON adverse effects

A

dizziness, dyspepsia, dry mouth, EPS, blurred vision, south, etc.

42
Q

Ziprasidone UNCOMMON adverse effects

A

abnormal gait, thirst, palpitation, hyperprolactinemia, etc.

43
Q

Ziprasidone RARE adverse effects

A

chest pain, feeling hot, pyrexia, sluggishness, gastroesophageal reflux, etc.

44
Q

Brexpiprazole

A

atypical antipsychotic
- partial agonist of D2 dopamine receptor
- Serotonin-dopamine activity modulator (SDAM)

45
Q

Brexpiprazole is used to treat what diagnoses?

A

schizophrenia, depression and major depressive disorder (MDD)

46
Q

Enzyme Inhibition

A

decreased drug clearance –> system accumulation = TOXICITY

47
Q

Enzyme induction

A

increased drug clearance –> decreased systemic drug level = treatment failure

48
Q

what can be filtered by Ro5?

A

particles that fall under:
- molecular wt < 500 Daltons
- Lipophilicty LogP <5
- H-bond donors <5
- H-bond acceptors <10

itx ii (4 decks)

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