Pharm III - Exam 4 > Antipsychotics > Flashcards

Antipsychotics Flashcards

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1
Q

Goals of acute treatment of schizophrenia

A
  • Relieve distressing psychotic symptoms
  • Induce remission
  • Minimize adverse effects
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2
Q

Goals of maintenance treatment of schizophrenia

A
  • Prevent relapse
  • Prevent re-hospitalization
  • Improve quality of life
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3
Q

What NT systems are implicated in schizophrenia?

A
  • Serotonin
  • Dopamine
  • Glutamate
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4
Q

Which NT system is NOT targeted by any antipsychotics currently?

A

Glutamate

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5
Q

What are the dopaminergic pathways in the CNS?

A
  1. Mesocortical
  2. Mesolimbic
  3. Nigrostriatal
  4. Tubero-infundibular
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6
Q

Function of mesocortical tract?

A
  • Cognition
  • Communication
  • Social function
  • Response to stress
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7
Q

Function of mesolimbic tract?

A
  • Arousal
  • Memory
  • Stimulus processing
  • Motivational behavior
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8
Q

Function of nigrostriatal tract?

A
  • Extrapyramidal system

- Movement

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9
Q

Function of tubero-infundibular tract?

A

Regulation of prolactin release

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10
Q

Dopamine antagonistic effect in mesocortical tract?

A
  • Relief of psychosis

- Akathisia

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11
Q

Dopamine antagonistic effect in mesolimbic tract?

A

Relief of psychosis

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12
Q

Dopamine antagonistic effect in nigrostriatal tract?

A

Movement disorders

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13
Q

Dopamine antagonistic effect in tubero-infundibular tract?

A

Hyperprolactinemia

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14
Q

1st generation vs. 2nd generation antipsychotics

A

Binding affinity is higher in 2nd generation so fewer side effects

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15
Q

What is the only antipsychotic that is NOT considered 1st line treatment?

A

Clozapine

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16
Q

MC used first generation antipsychotics (FGAs)?

A

Chlorpromazine
Fluphenazine
Perphenazine
Haloperidol

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17
Q

How do FGAs work?

A
  • D2 blocking in all 4 DA pathways
  • H1 blocking
  • M1 (cholinergic) blocking and A1 blocking
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18
Q

How are FGAs classified?

A

By potency for D2 blocking

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19
Q

What are the effects of low dose, high potency FGAs? Which FGAs?

A
  • Greater affinity for D2 receptors which means greater potential for extrapyramidal side effects, hyperprolactinemia
  • Fluphenazine, Perphenazine, Haloperidol
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20
Q

What are the effects of high dose, low potency FGAs? Which FGAs?

A
  • More likely to cause sedation, orthostatic hypotension (anticholinergic and antihistaminergic effects)
  • Chlorpromazine
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21
Q

Which FGAs are immediate acting and what route?

A

Haloperidol and chlorpromazine (IM)

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22
Q

Which FGAs are long acting depot formulations and what route?

A
  • IM biweekly or monthly

- Esters dissolved in sesame oil (haloperidol/fluphenazine decanoate)

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23
Q

What is the role for long acting depot formulation of FGAs?

A

Non-compliant patients with their oral meds

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24
Q

What is the role for immediate acting IM injections of FGAs?

A

Acutely psychotic/agitated patients (NOT meant to replace oral meds)

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25
Adverse effects of FGAs?
- H1 blocking: sedation, wt gain - M1 blocking: dry mouth, urinary retention, tachy, ED, cognitive dysfunction - A1 blocking: orthostatic hypotension, dizzy - QT prolongation (Torsades) - D2 blocking (endocrine): hyperprolactinemia - EPSEs (acute dystonia, akathisia, pseudoparkinsonism)
26
What are the CV effects of FGAs?
- A1 blocking: orthostatic hypotension, dizzy | - QT prolongation: Torsades (thioridazine, mesoridazine, haloperidol, pimozide)
27
Which FGAs have a black box warning for QT prolongation/Torsades?
Thioridazine and mesoridazine | QT prolong/Torsades also seen in haloperidol, pimozide
28
Types of EPSEs
- Acute dystonia - Akathisia - Pseudoparkinsonism - Tardive dyskinesias
29
Define acute dystonia
- Spasmodic or sustained muscle spasms and abnormal postures (often painful) - Treat as medical emergency!
30
When may acute dystonia occur with FGA therapy?
Within minutes to hours
31
Risk factors for acute dystonia
- Young males - High potency FGAs - Immediate release IM administration of FGAs
32
Treatment choices for acute dystonia
- Anticholinergics: benztropine, diphenhydramine - BZDs - IM or IV
33
Define akathisia
Combo of objective and subjective symptoms - Motor restlessness - Feeling of inner restlessness or compulsion to move - 20-40% w/high potency FGAs - Quetiapine and clozapine appear to have lowest risk of SGAs
34
What is akathisia frequently accompanied with?
Dysphoria
35
Which SGAs have lowest risk for akathisia?
Quetiapine and clozapine
36
Treatment of akathisia
- B blockers: propranolol, treatment of choice! - BZDs (CI in substance abuse pts) - Anticholinergics are NOT helpful
37
Define pseudoparkinsonism
- D2 blocking in nigrostriatal tract | - Resembles idiopathic Parkinson's disease
38
Cardinal symptoms of pseudoparkinsonism
1. Akinesia/bradykinesia 2. Resting tremor (pill rolling) 3. Cogwheel rigidity 4. Postural abnormalities
39
Treatment of pseudoparkinsonism
Anticholinergics: benztropine, diphenhydramine
40
When do symptoms of pseudoparkinsonism resolve with treatment?
- Symptoms begin to resolve within 3-4 days | - Minimum 2 wks treatment required for full response
41
What is used as treatment of pseudoparkinsonism if anticholinergics are contraindicated?
Amantadine
42
Define tardive dyskinesia and when it occurs in antipsychotic use
- Abnormal involuntary movements (increased when pt is aroused, decreased when pt is asleep) - Occurs late in relation to initiation of antipsychotic therapy - MUST monitor every 6 mos with AIMS
43
How to monitor tardive dyskinesia?
Abnormal Involuntary Movement Scale (AIMS) every 6 months
44
Prognosis of tardive dyskinesia
May be reversible early | Often irreversible
45
Risk factors for tardive dyskinesia
- Older age - EPSEs - Poor antipsychotic response - DM - Mood disorders - Females
46
Treatment of tardive dyskinesia
- Reassess need for continuing antipsychotic (switch to atypical agent) - High doses of Vit E NOT recommended (CV effects)
47
Define neuroleptic malignant syndrome
- Rare SE of FGAs (high potency) - Onset varies (early in treatment to months later) - Develops rapidly (over 24-72 hrs) - May be d/t disruption of central thermoregulatory process
48
Risk factors of neuroleptic malignant syndrome
Dehydration Organic mental disorders Exhaustion
49
Lab evaluations of neuroleptic malignant syndrome
- Leukocytosis w/left shift - Increased CK and LFTs - Myoglobinuria
50
Treatment of neuroleptic malignant syndrome
- D/c antipsychotic - Supportive care - DA agonists (bromocriptine, amantadine) - Dantrolene (muscle relaxant)
51
How can antipsychotics cause seizures?
Decrease the seizure threshold via GABA depletion
52
When is prophylaxis for seizures given with antipsychotics?
At high doses and in pts on other agents that lower seizure threshold
53
Highest risk for seizures with which antipsychotics?
Cozapine | Chlorpromazine
54
Which antipsychotics are more likely to cause thermoregulation side effects?
Low potency FGAs | Anticholinergic SGAs
55
Define poikilothermia
- Body temp adjustment to ambient temp | - Serious side effect in temp extremes
56
Define hyperpyrexia
- Danger in hot weather or during exercise | - Inhibition of sweating due to anticholinergic properties
57
How do SGAs work?
5HT blocking more than DA blocking
58
How do SGAs compare to FGAs?
- Greater efficacy for negative symptoms and cognitive deficits - Decreased risk of EPSEs, hyperprolactinemia - Absence (or near absence) of TD - More rapid dissociation from D2 receptor
59
When are all antipsychotics contraindicated?
Elderly pts w/dementia-related psychosis (increased risk of death)
60
SGAs and dopaminergic pathways
- Mesocortical: more 5HT receptors here - Mesolimbic: more D2 here - Nigrostriatal: many 5HT receptors - Tuberoinfundibular: many 5HT
61
Clozapine is specific for which DA tracts?
Mesolimbic | NOT nigrostriatal
62
Black box warnings of clozapine
- Agranulocytosis - Seizures - Myocarditis - Other CV and resp effects
63
When is clozapine used in schizophrenia?
Reserved for pts refractory to AT LEAST 2 other antipsychotics (3rd line)
64
When could clozapine be used earlier in schizophrenia treatment?
Pts with history of recurrent suicidality, violence, or comorbid substance abuse
65
How should clozapine be administered?
Cautious titration to minimize risks of hypotension, seizure, resp depression, sedation
66
Clozapine ADEs
- Sedation - Tachy - Hypersalivation - Dizzy - Wt gain - Agranulocytosis ETC ETC
67
Which antipsychotic has the highest seizure risk?
Clozapine
68
When is orthostatic hypotension more likely to occur with clozapine use?
More likely during initial dose titration
69
Black box warnings of Clozapine?
- Agranulocytosis - Seizures - Myocarditis - Other CV and resp effects
70
Clozapine drug interactions
- CYP1A2 inhibitors/inducers | - Other drugs that cause agranulocytosis or lower seizure threshold
71
Clozapine monitoring
- REMS for agranulocytosis (measure ANC) - EPSEs (AIMS every 6 months) - Lipid panel, fasting glucose every 6 months - Vitals multiple times daily during dose titration - Weekly wt and waist circumference
72
Risperidone ADEs
- Anxiety, somnolence, constipation, nausea, rash (common) - EPSEs and hyperprolactinemia - Orthostatic hypotension - Priapism (rare)
73
Risperidone drug interactions
- CYP2D6 inhibitors | - Other drugs that cause orthostasis
74
Risperidone monitoring parameters
- Prolactin levels every 6 months - EPSEs (AIMS every 6 months) - Lipid, fasting glucose every 6 months - Vital signs multiple times daily during dose titration - Weekly wt and waist circumference
75
ADEs of Olanzapine
- Dizzy, orthostatic hypotension, wt gain, akathisia (common) - Anticholinergic - Sedation - HyperTG, hyperlipid, hyperglycemia
76
Olanzapine drug interactions
- CYP1A2 - Clearance increased 30-40% in smokers - Plasma concentrations higher in females
77
Role of Quetiapine XR
- Replacement of IR dosing after steady state achieved - Pt can be switched directly to XR - Total daily XR dose is same as total daily IR dose
78
Quetiapine drug interactions
CYP3A4
79
Ziprasidone drug interactions
CYP3A4
80
Ziprasidone cautions
Can prolong QT interval (Torsades)
81
When should Ziprasidone be d/c?
Pts with QTc over 500 msec
82
Aripiprazole drug interactions
CYP3A4 inducers | CYP3A4 and CYP2D6 inhibitors
83
Aripiprazole cautions
Mild postural hypotension and sedation during initiation and dose titration
84
What is the active metabolite of Risperidone?
Paliperidone (9-hydroxyrisperidone)
85
How should Paliperidone be administered?
Tablet swallowed whole (do not chew, crush, divide)
86
What is Paliperidone?
Active metabolite of risperidone (9-hydroxyrisperidone)
87
ADEs of Paliperidone
Higher risk of EPSEs, hyperprolactinemia, QT prolongation than other atypical antipsychotics
88
Iloperidone drug interactions
CYP3A4 inhibitors or inducers | CYP2D6 inhibitors
89
Which SGAs increase the risk of QT prolongation?
``` AQIPZ Asenapine Quetipaine Iloperidone Paliperidone Ziprasidone ```
90
Which SGAs are most likely to cause wt gain?
Clozapine | Olanzapine
91
Which SGAs are most likely to cause diabetes?
Clozapine | Olanzapine
92
Which SGAs are most likely to cause hypercholesterolemia?
Clozapine | Olanzapine
93
What are the monitoring parameters for all antipsychotics?
- EPSEs (AIMS every 6 months) - Lipid panel, fasting glucose every 6 months - Vital signs multiple times daily during dose titration - Weekly wt gain and waist circumference
Pharm III - Exam 4
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