Lecture 4: Antipsychotics Flashcards

1
Q

Positive Symptoms Schizophrenia (7)

A
  1. hallucinations
  2. hostility
  3. excitability
  4. delusions
  5. suspiciousness/persecution
  6. conceptual disorganization
  7. grandiosity
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2
Q

Negative symptoms schizophrenia (5)

A

lessening or absence of normal behaviors and functions related to motivation and interest or verbal/emotional expression

  1. Blunted effect
  2. Alogia
  3. Avolition
  4. Asociality
  5. Adnhedonia
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3
Q

Blunted effect

A

negative symptom shcizophrenia

  • diminished facial and vocal
  • poor eye contact
  • minimal use gestures
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4
Q

Alogia

A

Negative sx schizophrenia

  • short to monosyllable answers to questions
  • avoids communication
  • uses few words
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5
Q

Avolition

A

negative sx schizophrenia

  • emotional withdrawal
  • apathy
  • poor grooming/hygiene
  • decreased involvement with work or school
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6
Q

Asociality

A

Negative sx schizophrenia

  • few friends/poor relationships
  • lack of motivation for relationships
  • reduced social interaction
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7
Q

Anhedonia

A

negative sx schizophrenia

  • difficulty or inability to anticipate future pleasure
  • few leisure activities
  • lack of interest in sexual activity
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8
Q

Goals of therapy (4)

A
  1. efficacy: reduction in threat/harm, improvement in acute psychosis
  2. stabilization: reduce postitive, negative, cognitive sx, medication adherance
  3. Maintenance: control/remission sx, baseline return, relapse prevention
  4. Adverse effects: adherence to medication, management ADRS
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9
Q

American Psychiatric Association Guidelines

tx recommentations (4 steps)

A
  1. tx with antipsychotic
    - monitor for effectivement and side effects
    - continue antipsychotics if symptoms improve
  2. Clozapine
    - tx resistant schizophrenia
    - suicidality remains desire other tx
  3. Tx acute dystonia (involuntary muscle movements) with an anticholinergic rx
  4. Treat moderate to severe tardive dyskinesia with VMAT2 inhibitor
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10
Q

Tx recommendations (4)

A
  1. any antipsychotics could be considered for 1st line
    - EXCP: clozapine & lumateperone
    - Adequate trial=apropriate dosing for 2-6 weeks
  2. After failure: switch one of the above
  3. third line: clozapine
    - adequate trial: appropriate dosing for 12 + weeks
  4. beyond: augmenting clozapine, multiple agents, ECT
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11
Q

Adequate trial for antipsychotics

A

appropriate dosing for 2-6 weeks

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12
Q

Exceptions to the antipsychotics 1st line of defense rule

A
  1. clozapine

2. lumateperone

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13
Q

Clozapine as third line

A

adequate dosing for 12+ weeks

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14
Q

1st Generation/ typical antipsychotics

Mechanism (4)

A

M: 1) dopamines- (DA)D2 receptor blockade
-therapeutic effect, EPS

  1. muscarinic- M1 receptor blockade
  2. histaminic- H1 receptor blockade
  3. Alpha- Aa1 receptor blockade
    * agents differ in potency and receptor affinity
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15
Q

Second generation/atypical antipsychotics

MOA
EXCP

A

M: 1) similar to 1st generation antipsychotics

  • increase D2 receptor dissociation
  • additional serotonin 5HT2a antagonism

EXCP: aripiprazole, brexiprazole, and caripraszine- partial agonists at D2 receptors

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16
Q

D-HAMS receptors assoc. with antipsychotic therapy

A
  1. Dopaminergic
  2. Histamanic
  3. Adrenergic
  4. Muscarinic
  5. Serotonergic
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17
Q

Dopaminergic receptor (3)

A

therapeutic effects

extrapyramidal side effects

hyperprolactinemia

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18
Q

Histaminic receptor (2)

A

sedation and wight gain

19
Q

Adrenergic receptor (2)

A

postural hypotension and reflex

tachycardia

20
Q

Muscarinic receptors (6)

A

anticholinergic-dry mouth, contipation, urinary retention, blurred vision, decreased cognition

21
Q

ALL ANTIPSYCHOTIC AE (4)

A
  1. mortality and dementia
  2. FDA boxed warning
  3. elderly: dementia, related psychosis
  4. meta-analysis of 17 placebo-controlled trias: 1.6 x more likely to dies compared to placebo
    CAUSE: varied, but included cardiovascular and infectious
22
Q

Precautions for all/most FGAs (first generation antipsychotics) (8)

A
  1. seizure disorders
  2. neuroleptic malignant syndrome
  3. movement disorders
  4. blood dycrasias
  5. inability to adjust to extreme heat
  6. cardiovascular disease
  7. hyperprolactinemia
  8. dysphagia
23
Q

AE inhaled loxapine

Indication
box warning (3)
A

I: ACUTE tx agitation in schizophrenia/bipolar disorder in adults

W: 1. potential cause respiratory distress and arrest

  1. can only be used in an enrolled facility that can intubate/ventilate patients
  2. do not use in patients with asthma, COPD, lung disease or physical exam positive for respiratory problems
24
Q

Precautions for all/most SGAs (9)

A
  1. seizures
  2. neuroleptic malignant synfrome
  3. metabolic abnormalities the can increase cardiovascular rx
  4. hyperprolactinemia
  5. blood dyscrasia
  6. orthostasis and syncope
  7. Suicidality
  8. Dysphagia
  9. inability to adjust to extreme heat
25
Q

Extrapyramidal SE (4)

A

*more commonly seen with typical antipsychotic

  1. acute dystonia
  2. pseudoparkinsonism
  3. akathisia
  4. tardive dyskinesia
26
Q

Acute dystonia (extrapyramidal side effect)

A
  1. occurs within 1-3 days
  2. spastic muscle contraction, usually head & neck
  3. increased in males, younger, high doses, high potency

*manage with anticholinergic agent, Diphenhdyramine (benadryl) or Benztopine (cogentin)

27
Q

Pseudoparkinsonism (extrapyramidal side effect) (4)

A
  1. occurs within 1-3 months imitation
  2. symptoms resemble parkinson’s
    - gait disturbances, cogwheel rigifity, bradykinesia, etc.
  3. increased in females, elderly, high doses, high potency
  4. Manage by decreases dose, anticholinergic agents
    - benztropine
    - duphenhydramine
    - tryhexyphenidyl
28
Q

Akathisia (extrapyramidal) (4)

A
  1. occ. first 3 months
  2. sx include subjective restlessness, jitteriness, fidgeting, pacing
  3. increased in high dose, high potency, fast titration, concomitant stimulant use
  4. Manage by decreasing dose, change agent, pharmacologically
    - propranolol
    - lorazepam
29
Q

Tardive Dyskinesia (extrapyramidal)

A
  1. 3% per year
    typical > atypicals
  2. sx=repetative involunatry movements, generally involving mouth and face
  3. can be irreversible
  4. increased in females, elderly, DM, affective disorders, early EPS deeloplemtn, alcohol use
  5. Manage by decreased minimum effective dose, atypical meds
    - valbenazine, deutetrabenazine
30
Q

Neuroleptic Malignant syndrome

sx(4)

A
  • rare but life threatening, 1% occurance
  • sx: fever, lead pipe rigidity, mental status change, autonomic dysfunction
  • manage: supportive care, d/c antipsychotic
    1. bromocriptine
    2. dantrolene
31
Q

QTC prolongation

caution
leas common rx
most common

A
  1. caution in pre-existing abnormalities
  2. least: ariprazole, lurasidone
  3. Most: ziprasidone, thioridazine with box warning
32
Q

Endocrine adverse effects

A
  1. hyperprolactinemia from hypothalamic dopamine blockade
    - glactorrhea
    - gynecomastia
    - amenorrhea
    - sexual dysfunction

more common with typical antipsychotics

33
Q

Metabolic Adverse effects

A

*more common with atypical

  • central obesity
  • high blood pressure
  • high triglycerides
  • low HDL-cholesterol
  • insulin resistance
34
Q

TypicalsL Misc. effects

  1. thioridazine
  2. low potency agents
  3. all agents
A
  1. thioridazine: pigmentary retinopathy (max dose 800 mg/day)
  2. low potency agents: skin discoloration with sun exposure
  3. all agents: transient elevations in LFTS
35
Q

Atypical drugs and their adverse effects (4)

“apines” (3)
“peridones” (3)
“sidones” (3)
partial agonist

A
  1. “apines” sedation, metabolic, anticholinergic
  2. “peridones” less sedation, some metabolic, more EPS
  3. Admin: asenapine (TD, SL) Sidones: with food, low metabolic rx, med EPS rx
  4. Partial agonists: lowest metabolic rx, no prolactin increase, more akathisia
36
Q

Clozapine rxns (4)

A
  1. seizures: dose dependent
  2. orthostatic, syncope, cradycardia, cardiac arrest: avoid combination with benzodiazepines, rx greatest during titration periods
  3. myocarditis and cardiomyopathy: baseline ECG recommended, eosinophilia may be early indicator
  4. agranulocytosis: CBC monitoring **, enrollment in clozapine REMS program
37
Q

Pregnancy rx

A
  1. concern: movement disorders, withdrawal following birth
    - data lacking in general, mostly historical
    - clozapine and lurasidone may have less rx
38
Q

Lactation rx

A

should be avoided

loses doeses and close monitoring

39
Q

Pediatrics rx

A
  1. ped and adolescents more susceptible to metabolic changes (wt gain)
  2. schizophrenia in pets is rare
    - psychotherapeutic interventions should b used in combination
    - antipsychotics approved for autism: aripiprazole and risperidone
40
Q

Elderly antipsychotics

A
  1. behavioral and psychological symptoms of dementia (BPSD)
  2. anxiety, agitation, hypnosis
    - rationale: reduce use of benzodiazepines
    - depression augmentation
  3. less common: Parkinson’s assoc. psychosis
41
Q

Parkinson’s disease psychosis

mOA
indication
dose
AE

A

Pimavancerin/nuplazid

MOA: inverse agonist of 5-HT2a

indicated only for PD related psychosis

Dosing: 24 mg PO once daily
-strong CYP3A4 inhibitors (i.e. ketoconazole) 10 mf daily

  • AE: peripheral edema, confusion, hallucinations, nausea, orthostasis, QTc prolongation
  • same boxed warning for death in dementia
42
Q

How to choose medications?

A
  1. what has pt. responded to in the past?
  2. What have family members responded to?
  3. Does the patient have comorbidities to consider when choosing agents?
  4. rx cost?
43
Q

How to educate pt?

A
  1. tx as chronic disease
    - rx of relapse high
    - most need lifelong therapy
  2. administration specifics
    - agents needing food
    - keeping f/u with LAIs, PO overlap
    - dissolvine asenapine-no food/water x10 minutes
  3. side effects concern
44
Q

Summary

A
  1. antipsychotics exert their effects through modulation of NTSM recpetors in brain
    - block D2, 5HT2a, Etc
  2. both 1st and 2nd generation antipsychotics have considerable, but varying adverser effect profiles
  3. medication compliance and efficacy may bot differ significantly between most agents
    - multiple medication trials may be necessary