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Psych Pharm > Antipsychotic Drugs > Flashcards

Antipsychotic Drugs Flashcards

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1
Q

definition of psychosis

A
  • major mental disorder w/ following symptoms
    1. personality is seriously disorganized
    2. contact w/ reality is impaired
    3. ability to think, perceive, and judge is impaired
    4. ability to communicate and relate to others is impaired
    5. can’t cope w/ environment
    6. can’t meet ordinary demands of life
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2
Q

criteria for schizophrenia

A
  • 2 or more, each present for a significant proportion of time for 1 month
    1. delusions
    2. hallucinations
    3. disorganized speech
    4. grossly disorganized or catatonic behavior
    5. negative symptoms
  • social/occupational dysfunction
  • at least 6 months
  • substance abuse and general medical conditions have been ruled out
    • in presence of autism, hallucinations or delusions present for over 1 month
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3
Q

positive symptoms of schizophrenia

A
  • delusions, hallucinations, disorganized speech, disorganized or catatonic behavior
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4
Q

negative symptoms of schizophrenia

A
  • impoverished thoughts
    deficits of attention
    blunt affect
    lack of initiative
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5
Q

dopamine receptors

A
  1. D1 : activated by AC (Gs)

2. D2 : Gi

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6
Q

Typical antipsychotics MOA

A
  • dopamine D2 blockers
  • produces extrapyramidal symptoms (EPS)
  • elevated PRL levels
  • equally effective but differ in potency/side effects
  • largely effective for positive symptoms
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7
Q

Atypical antipsychotics MOA

A
  • share D2 and 5HT2A antagonism in common

- addition of 5HT2A blockade my reduce EPS and improve efficacy for negative symptoms

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8
Q

What are the antipsychotics

A

phenothiazines
thioxanthenes
butyrophenones and diphenylbutylpiperidines

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9
Q

Phenothiazines

A
  • Aliphatic side chain: chlropromazine, low potency

- Piperazine group side chain: fluphenazine, perphenazine. Potent

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10
Q

Butyrophenones

A

Haloperidol - high potency

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11
Q

Clozapine

A

low potency, atypical

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12
Q

Risperidone

A

5HT2/D2 antagonist

  • limited EPS at low doses
  • only approved agent for use in kids and teens
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13
Q

Aripiprazole

A

D2 partial agonist - reduces actions of full agonist

  • 5HT2A antagonists, 5HT1A partial agonists
  • lower incidence of side effects
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14
Q

Ziprasidone

A

5HT2A, 5HT1a, 5HT2C/D2 antagonist

- limited EPS

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15
Q

Lurasidone

A

D2 and 5HT2A antagonist
5HT1A partial agonist
risk of EPS present

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16
Q

Neuroleptic syndrome

A

suppression of spontaneous movements and complex behavior

  • reduced initiative and interest in environment
  • decreased manifestations of emotion or affect
  • psychotic symptoms disappear over time
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17
Q

CNS effects of antipsyhcotics

A
  1. Cerebral cortex - minimal adaptive changes in dopamine system, can lower seizure thresholds
  2. Basal Ganglia - initially increase DA metabolism, synthesis and firing rate. Antipsychotics don’t really occur here
  3. Limbic system - thought to be site of antipsychotic effects, anticholinergics don’t block therapeutic effect
  4. Hypothalamus - increased PRL, little tolerance, avoid in pts w/ established breast carcinoma
  5. Brainstem - little effect on respiration, decreased vasomotor reflexes at low doses
  6. CTZ -
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18
Q

What effect do the following have on Prl secretion?

  1. All typicals
  2. Risperidone
  3. Clozapine
  4. Olanzapine
  5. Ziprasidone
  6. Quetiapine
  7. Aripiprazole
A
  1. increased
  2. increased
  3. little increase
  4. little increase
  5. little increase
  6. no increase
  7. no increase
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19
Q

clinical consequences of sustained hyperPRL

A

sexual dysfunction, amenorrhea, gynecomastia/galactorrhea, hypoestrogenism/osteopnia

20
Q

other organ system effects of antipsychotics

A
  1. ANS - complex and unpredictable
  2. renal system - chlorpromazine may be antidiuretic
  3. Hepatic system - no characteristic effects, may be toxin in pts w/ liver dz
  4. Endocrine system - chlorpromazine (impaired glucose tolerance, decreases insulin release). Clozapine, risperidone, aripiprizole, ziprasidone, olanzepine, and quetiapine all increased risk of type 2 DM
  5. CV system - direct effects on heart and vessels and indirect effects via CNS and ANS. Mild orthostatic hypotension. (more w/ chlorpromazine, thioridazine. less w/ haloperidol, loxapine, risperidone. tolerance develops)
  6. Misc : may increase Ach turnover (basal ganglia), inverse relationship btw antimuscarinic potency and EPS
21
Q

Side effects of antipsychotics

A
  • high TI
  • anticholinergic effects: nasal stuffiness, dry mouth, blurred vision, constipation, CV
  • acute dystonia, akathesia, parkinsonian syndrome, NMS, perioral tremor, tradive dyskinesia
  • jaundice
  • blood dyscrasis
  • skin rxn
  • wt gain
22
Q

what is acute dystonia

A

muscle spasma: facial grimacing, torticollis, oculogyeric crisis
- treat w/ anticholinergic antiparkinsonian agents

23
Q

What is akathesia

A
  • strong subjective feelings of distress or discomfort often referrred to the legs. “ants in pants”
  • treat by decreasing dose, add antiparkinsonian agent, antianxiety agent or propranolol
24
Q

Parkinsonian syndrome

A
  • akinesia, mask facies, decreased arm movement, rigidty, tremor
  • treat w/ anticholinergic antiparkinsonian agent, amantadine
25
Q

NMS

A

rare, fever, severe parkinsonism w/ catatonia

  • fluctuations in coarse tremor intensity
  • autonomic instability
  • elevated creatine kinase
  • myoglobinemia
  • high morality
26
Q

treatment for NMS

A
  • stop antipsyhcotic
  • supportive care
  • dantrolene or bromocriptine
27
Q

Perioral tremor

A

rare, rabbit syndrome

- treat w/ anticholinergic agent, stop neuroleptic

28
Q

Tardive dyskinesia

A

repetitive, quick choeriform movements of face eyelids, mouth, tongue, extremities or trunk

  • no real treatment
  • discontinue antipsychotic
  • symptoms fade w/ time
29
Q

Jaundice side effect

A
  • occurs 2nd-4th week w/ chlorpromazine
  • HSR rxn
  • mild
    change agents
30
Q

Blood dyscrasis side effect

A

mild leukocytosis, leukopenia (may be a sign of impending agranulocytosis), eosinophilia
- especially important when using clozapine

31
Q

Skin rxn side effect

A
  • urticaria or dermatitis
  • 5% of pts on chlorpromazine
  • more common w/ phenothiazines
  • occurs in 1st 8 weeks
  • skin clears w/ discontinuation
  • photosensitivty
32
Q

Wt gain side effect

A
  • clozapine, olanzapine more likely
  • risperidone, quetiapine - intermediate risk
  • ziprasidone, aripiprazole, asenapine - less likely
  • increased risk of type 2 DM, HTN, and HLD
33
Q

incidence of metabolic syndrome on atypical antipsychotis

A
  1. olanzapine - high
  2. quetiapine - mod
  3. risperidone - mod
  4. zisprasidone - low
  5. aripiprazole - low
34
Q

PK of antipsychotics

A
  • highly lipophilic
  • highly protein and membrane bound
  • accumulates in high blood supply tisssue
  • crosses placental barrier and enters breast milk
35
Q

metabolism of antipsychotics

A
  • oxidation main route: hepatic microsomal oxidase and conjugation
  • most metabolites inactive
36
Q

drug interactions of typical antipsychotics

A
  • metabolized by 2D6 and 3A4
  • dont’ induce CYP enzymes
  • may inhibit 2D6 and raise levels of many TCAs and SSRIs
37
Q

Treatment for following disorders

  1. schizophrenia
  2. bipolar disorders w/ psychotics features
  3. schizoaffective disroder
  4. major depressive disorder w/ psychotic features
A
  1. antipsychotics
  2. mood stabilizers and/or antipsychotics
  3. antipsychotics, w/ mood stabilizers and/or antidepressants
  4. ECT and/or antidepressant med and/or antipsychotics
38
Q

long acting depot antipsychotics

A
  1. slow release, combined w/ base AP w/ a fatty acid (decanoic acid)
  2. alcohol group of drug is esterified by acid = increased solubility in oil
  3. considered for pts w/ several relapses, pts who have compliance problems, when oral absorption is poor
39
Q

Misc uses for antipsychotisc

A
  1. N/V
  2. Alcoholic hallucinosis
  3. neuropsychiatric diseases marked by movement disorders: tourettes, HD, intractable hiccup
40
Q

What are the 2nd gen antipsychotics

A 
Aripirazole
Clozapine
Olanzapine
Palperidone
Quetiapine
Risperidone
Ziprasidone
41
Q

What 2nd gens are more likely to casue DM and weight gain

A

Clozapine and olanzapine

- palperidone, quetiapine, risperidone also do both but a bit less

42
Q

2nd gens that cause EPS

A
  • Risperidone -most likely
  • Palperidone and Aripirazole - next
  • Ziprasidone and Olanzapine
43
Q

2nd gens that cause QT prolongation

A
  • Ziprasidone - most

- others do a little

44
Q

2nd gens that cause PRL secretion

A
  1. most = risperidone and palperidone

2. next = ziprasidone and olanzapine

45
Q

2nd gen drugs w/ highest potential for CYP interactions

A

Aripiprazole
Quetiapine
Risperidone
Ziprasidone

Psych Pharm (7 decks)

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