22.1 Pharmacotherapy: Antipsychotics Flashcards
(46 cards)
1
Q
“antipsychotics” used to be called what? (1)
A
“neuroleptics”
2
Q
Describe: Overall mechanism of action of antipsychotic (1)
A
block, to varying degrees, DA activity in target brain pathways
3
Q
Antipsychotic described for what? (2)
A
- primarily indicated for psychotic symptoms in: schizophrenia and related disorders, manic episodes, depressive episodes, substance use, medical conditions (i.e. neoplasm)
- other uses: treatment-resistant MDD, severe GAD, complex PTSD, severe OCD, borderline PD, behavioural symptoms of dementia, delirium, Tourette Syndrome, substance abuse in dual diagnosis, Huntington’s disease, ASD, impulse control disorders
- adjunctive management of agitation, aggression, severe anxiety, severe sleep difficulties when sedative-hypnotics are contraindicated
4
Q
Describe onset: Antipsychotic (2)
A
- rapid calming effect and decrease in agitation;
- thought disorder responds in 1-4 wk
5
Q
Name reasons to combine antipsychotics (1)
A
- no reason to combine two or more antipsychotics
6
Q
Name effectiveness of antipsychotics (3)
A
- all antipsychotics are equally effective, except for clozapine (considered to be most effective in treatment-refractory psychosis)
- atypical antipsychotics (second generation) are as effective as typical (first generation) antipsychotics but are thought to have better adverse effect profiles; main difference is lower risk of EPS and TD
- choose a drug to which the patient has responded to in the past or that was used successfully in a family member
7
Q
Describe duration antipsychotics (2)
A
- if no response in 4-6 wk, switch drugs
- duration: minimum 6 mo and usually for life in most patients with primary psychotic disorders; variable for other indications
8
Q
Name Dopamine Pathways Affected by Antipsychotics (4)
A
- Mesolimbic
- Mesocortical
- Nigrostriatal
- Tuberoinfundibular
9
Q
Describe effects and associated pathology of this dopamine pathway affected by antipsychotic: Mesolimbic (2)
A
- Effects: Emotion orginiation, reward
- Associated Pathology: HIGH dopamine causes positive symptoms of schizophrenia (delusions, hallucinations)
10
Q
Describe effects and associated pathology of this dopamine pathway affected by antipsychotic: Mesocortical (2)
A
- Effect: Cognition, executive function
- Associated Pathology: LOW dopamine causes negative symptoms of schizophrenia
11
Q
Describe effects and associated pathology of this dopamine pathway affected by antipsychotic: Nigrostriatal (2)
A
- Effects: Movement
- Associated pathology: LOW dopamine causes EPS
12
Q
Describe effects and associated pathology of this dopamine pathway affected by antipsychotic: Tuberofundibular (2)
A
- Effect: Prolactin hormone release
- Associated pathology: LOW dopamine causes hyperprolactinemia
13
Q
Describe: Long-Acting Preparations of antipsychotics (6)
A
- antipsychotics formulated in oil for IM injection
- received on an outpatient basis
- indications: individuals with schizophrenia or other chronic psychosis who relapse because of non- adherence
- should have been exposed to oral form prior to first injection
- dosing: start at low dosages, then titrate every 2-4 wk to maximize safety and minimize side effects
- side effects: risk of EPS, parkinsonism, increased risk of NMS
14
Q
Describe: Canadian Guidelines for the Treatment of Acute Psychosis in the Emergency Setting (4)
A
- haloperidol 5 mg IM ± lorazepam 2 mg IM
- loxapine PO 25 mg ± lorazepam 2 mg IM
- olanzapine 2.5-10 mg (PO, IM, quick dissolve)
- risperidone 2 mg (M-tab, liquid)
15
Q
Compare Typical (First Generation) vs. Atypical (Second Generation) Antipsychotics: Mechanism
A
- Typical: Block postsynaptic dopamine receptors
- Atypical:
- Block postsynaptic dopamine receptors (D2)
- Block serotonin receptors (5-HT2) on presenaptic dopaminergic terminals, triggering DA release and reversing DA blockade in some pathways
16
Q
Compare Typical (First Generation) vs. Atypical (Second Generation) Antipsychotics: Pros
A
- Typical:
- Inexpensive
- Plenty of injectable forms are available
- Atypical:
- Fewer EPS
- Low risk of tardive syndroms
- Mood stabilizing effects
17
Q
Compare Typical (First Generation) vs. Atypical (Second Generation) Antipsychotics: Cons
A
- Typical:
- More EPS
- Tardive syndromes long-term
- Not mood stabilizing
- Atypical:
- Expensive
- Few injectable forms available
- Metabolic side effects (weight gain, hyperglycemia, lipid abnormalities, metabolic syndromes)
- Exacerbation (or new onset) of obsessive behaviour
18
Q
Name: Commonly Used Atypical Antipsychotics (5)
A
- Risperidone (Risperdal®)
- Olanzapine (Zyprexa®, Zydis®)
- Quetiapine (Seroquel®)
- Clozapine (Clozaril®)
- Ariprazole (Abilify®)
19
Q
Name advantages: Risperidone (Risperdal®) (2)
A
- Lower incidence of EPS than typical antipsychotics at lower doses (<8 mg)
- Associated with less weight gain compared to clozapine and olanzapine
20
Q
Name disadvantages relative to other SGAs: Risperidone (Risperdal®) (7)
A
- Highest risk of EPS/TD among SGAs- avoid if high risk for EPS or existing movement disorder or elderly
- Elevated prolactin
- Sexual dysfunction
- Galactorrhea
- Gynecomastia
- Menstrual disturbance
- Infertility
21
Q
Name formulations: Risperidone (Risperdal®) (2)
A
- Quick dissolve (M-tabs)
- Long- acting (Consta®)
22
Q
Name advantages: Olanzapine (Zyprexa, Zydis) (3)
A
- Better overall efficacy compared to haloperidol
- Well tolerated
- Low incidence of EPS and TD
23
Q
Name disadvantages relative to other SGAs: Olanzapine (Zyprexa, Zydis) (2)
A
- Weight gain and metabolic effects - avoid in DM
- Sedating - avoid if high risk for falls or fracture
24
Q
Name formulations: Olanzapine (Zyprexa, Zydis) (2)
A
- Quick dissolve formulation (Zydis®) used commonly in ER setting for better compliance
- IM form available
25
Name advantages: Quetiapine (Seroquel) (2)
* Associated with less weight gain compared to clozapine and olanzapine
* **Mood stabilizing**
26
Name disadvantages relative to other SGAs: Quetiapine (Seroquel) (2)
* **Sedating/ortho hypotension** - avoid if high risk for falls or fracture
* **QT prolongation in high doses** - caution if cardiac risk
27
Name advantages: Clozapine (Clozaril®) (3)
* **Most effective** for treatment-resistant schizophrenia
* **Does not worsen tardive symptoms; may treat them**
* Approximately 50% of patients benefit, especially paranoid patients and those with onset after 20 yr
28
Name disadvantages relative to other SGAs: Clozapine (Clozaril®) (6)
* **Weight gain and metabolic effects** - avoid in DM
* **Sedating/ortho hypotension** - avoid if high risk for falls or fracture
* Potentially severe **constipation** - avoid if risk of fecal impaction or bowel perforation
* **Cardiomyopathy** – caution if existing heart disease
* **Seizures** – caution if seizure disorder
* **Agranulocytosis** (1%) – avoid in existing leukopenia/ neutropenia
29
Name considerations: Clozapine (Clozaril®) (2)
* **Weekly blood counts for 6 mo, then q2wk**
* Do not use with other drugs that may cause bone marrow suppression due to risk of agranulocytosis
30
Name advantages: Aripiprazole (Abilify®) (3)
* Less weight gain and risk of metabolic syndrome compared to olanzapine
* a lower incidence of EPS compared to haloperidol
* **mood stabilizing**
31
Name disadvantages relative to other SGAs: Aripiprazole (Abilify®) (2)
* Insomnia
* akathisia
32
Classify commonly used atypical antipsychotics according to risk of weight gain (Risperidone, Clozapine, Quetiapine, Olanzapine)
Risk of weight gain: Clozapine \> Olanzapine \> Quetiapine \> Risperidone
33
Describe: Neuroleptic Malignant Syndrome (3)
* psychiatric emergency
* due to strong DA blockade; increased incidence with high potency and depot antipsychotics
* risk factors
* medication factors: sudden increase in dosage, starting a new drug
* patient factors: medical illness, dehydration, exhaustion, poor nutrition, external heat load, male, young adults
* mortality: 5%
34
Describe clinical features: Neuroleptic Malignant Syndrome (5)
* tetrad:
* mental status changes (usually occur first)
* fever
* rigidity
* autonomic instability
* develops over 24-72 h
35
Describe labs: Neuroleptic Malignant Syndrome (3)
* ⬆️ creatine phosphokinase
* leukocytosis
* myoglobinuria
36
Describe tx: Neuroleptic Malignant Syndrome (6)
* supportive
* discontinue antipsychotic drug
* hydration
* cooling blankets
* **dantrolene** (hydrantoin derivative, used as a muscle relaxant)
* **bromocriptine** (DA agonist)
37
Name extrapyramidal sx of antipsychotics (4)
* Dystonia
* Akathisia
* Pseudoparkinsonism
* Dyskinesia
38
Describe this extrapyramidal sx in antipsychotics: Dystonia
* Acute or Tardive
* High Risk Groups
* Presentation
* Onset
* Acute or Tardive: Both
* High Risk Groups: Acute: Young asian and black males
* Presentation: Sustained abnormal posture; torsions, twisting, contraction of muscle groups; muscle spasms (i.e. oculogyric crisis, laryngospasm, torticollis)
* Onset:
* Acute: within 5d
* Tardive: \>90d
39
Describe this extrapyramidal sx in antipsychotics: Dystonia
* Treatment (2)
Acute:
* benztropine
* diphenhydramine
40
Describe this extrapyramidal sx in antipsychotics: Akathisia
* Acute or Tardive
* High Risk Groups
* Presentation
* Onset
* Acute or Tardive: Both
* High Risk Groups: Older females
* Presentation:
* Motor restlessness; crawling sensation in legs relieved by walking
* very distressing, increased risk of suicide and poor adherence
* Onset:
* Acute: within 10d
* Tardive: \>90d
41
Describe this extrapyramidal sx in antipsychotics: Akathisia
* Treatment (4)
* Acute:
* lorazepam
* propranolol
* diphenhydramine
* reduce dose or change antipsychotic to lower potency
42
Describe this extrapyramidal sx in antipsychotics: Pseudoparkinsonism
* Acute or Tardive
* High Risk Groups
* Presentation
* Onset
* Acute or Tardive: Acute
* High Risk Groups: Older females
* Presentation:
* Tremor; rigidity (cogwheeling); akinesia; postural instability (decreased/absent arm- swing, stooped posture, shuffling gait, difficulty pivoting)
* Onset: Acute: within 30 d
43
Describe this extrapyramidal sx in antipsychotics: Pseudoparkinsonism
* Treatment (2)
Acute:
* benztropine
* reduce dosage or change antipsychotic to low potency atypical antipsychotic
44
Describe this extrapyramidal sx in antipsychotics: Dyskinesia
* Acute or Tardive
* High Risk Groups
* Presentation
* Onset
* Acute or Tardive: Tardive
* High Risk Groups: Older patients
* Presentation:
* Purposeless, constant movements, involving facial and mouth musculature
* less commonly – the limbs; rarely, the diaphragm ("hiccups")
* Onset: Tardive: \>90d
45
Describe this extrapyramidal sx in antipsychotics: Dyskinesia
* Treatment
* no good treatment
* may try clozapine
* discontinue drug or reduce dosage
46
Describe use of anticholinergic agents with antipsythotics (3)
* types
* benztropine (Cogentin®) 2 mg PO, IM, or IV OD (1-6 mg)
* diphenhydramine (Benadryl®) 25-50 mg PO/IM qid
* do not routinely prescribe with antipsychotics
* give anticholinergic agents only if at high risk for acute EPS or if acute EPS develops
* do not give these for tardive syndromes because they worsen the condition
