Chapter 26: Antipsychotics -use in Schitzophrenia

Question 1

antipsychotic agents

Answer 1

Chemically diverse group of compounds​

Used for diverse spectrum of psychotic disorders​

Schizophrenia, delusional disorders, bipolar disorders, depressive psychoses, and drug-induced psychoses​

Also used to suppress emesis and to treat Tourette syndrome and Huntington chorea​

Should not be used to treat dementia in the older adult

Question 2

FGA

Answer 2

First-generation antipsychotics (FGAs) or conventional antipsychotics​

Block receptors for dopamine in the central nervous system (CNS)​

Cause serious movement disorders known as extrapyramidal symptoms (EPS)

Question 3

SGA

Answer 3

Second-generation antipsychotics (SGAs) or atypical antipsychotics​

Produce only the moderate blockade of dopamine receptors; stronger blockade for serotonin​

Fewer EPS

Question 4

schitzo clinical presentation

Answer 4

Disordered thinking and reduced ability to comprehend reality ​

Three types of symptoms

Question 5

positive schitzo s/sx

Answer 5

Exaggeration or distortion of normal function​

Hallucinations​

Delusions​

Agitation​

Tension​

Paranoia

Question 6

neg schitzo s/sx

Answer 6

Loss or diminution of normal function​

Lack of motivation​

Poverty of speech​

Blunted affect​

Poor self-care​

Social withdrawal​

​

Question 7

cognitive schitzo s/sx

Answer 7

Disordered thinking​

Reduced ability to focus attention​

Prominent learning and memory difficulties​

Subtle changes may appear years before symptoms become florid​

Florid changes: Thinking and speech may be completely incomprehensible to others

Question 8

schizo clinical presentation: acute episodes

Answer 8

Delusions (fixed false beliefs) and hallucinations are frequently prominent

Question 9

schizo clincal presentation: residual s/sx

Answer 9

Suspiciousness; poor anxiety management; and diminished judgment, insight, motivation, and capacity for self-care

Question 10

schizo long-term course

Answer 10

Acute exacerbations separated by intervals of partial remission

Question 11

etiology of schizo

Answer 11

Genetic​

Perinatal​

Neurodevelopmental​

Neuroanatomic factors ​

Excessive activation of CNS receptors for dopamine​

Insufficient activation of CNS receptors for glutamate​

Question 12

FGA classification

Answer 12

Classification by potency​:
Low potency: Chlorpromazine​
Medium potency​
High potency: Haloperidol

Chemical classification​
Five major chemical categories​
Phenothiazines and butyrophenones​
Drugs in all groups equivalent with respect to antipsychotic actions

Question 13

FGA MOA

Answer 13

Conventional antipsychotic drugs block a variety of receptors within and outside of the CNS​

Suppress symptoms of psychosis by blocking dopamine2 receptors in the mesolimbic area of the brain​

Adverse effects are a result of blocking receptors for dopamine, acetylcholine, histamine, and norepinephrine

Question 14

FGA therapeutic actions

Answer 14

Schizophrenia is the primary indication for antipsychotic drugs ​

These drugs suppress symptoms during acute psychotic episodes ​

Continued use reduces the risk of relapse

Question 15

FGA ADR: EPS

Answer 15

Acute dystonia​

Oculogyric crisis: upward dievation of eyes ​

Opisthotonus ​

Joint dislocation ​

Impaired respiration​

Anticholinergic medication (e.g., benztropine and diphenhydramine)​

Some manifestations of EPS are IRREVERSIBLE​

It is crucial to monitor patients treated with antipsychotics for EPS

Parkinsonism: Bradykinesia, mask-like facies, drooling, tremor, rigidity, shuffling gait, cogwheeling, and stooped posture

Akathisia: Pacing and squirming brought on by an uncontrollable need to be in motion

Tardive dyskinesia: Choreoathetoid movements of the tongue and face; lip-smacking movements; tongue flicks out in a “fly-catching” motion; slow, worm-like movement of the tongue; and involuntary movements of the limbs, toes, fingers, and trunk

Question 16

FGA ADR: NMS

Answer 16

Rare but serious reaction​

Risk of death without treatment​

“Lead pipe” rigidity, sudden high fever, sweating, autonomic instability, dysrhythmias, fluctuations in blood pressure, altered level of consciousness, and seizures or coma may develop​

Death can result from respiratory failure, cardiovascular collapse, dysrhythmias, and other causes

Question 17

nms TX

Answer 17

Supportive measures​

Drug therapy: Dantrolene and bromocriptine​

Immediate withdrawal of antipsychotic medication

Question 18

FGA ADR: other

Answer 18

Other adverse effects​

Anticholinergic effects​:
Dry mouth, blurred vision, photophobia, urinary hesitancy, constipation, and tachycardia​

Orthostatic hypotension​:
Antipsychotic drugs promote orthostatic hypotension by blocking alpha1-adrenergic receptors on blood vessels

Sedation​

Neuroendocrine effects​

Seizures​

Sexual dysfunction​

Dermatologic effects​

Agranulocytosis​

Severe dysrhythmias

Question 19

FGA physical and psychologic dependence

Answer 19

Development of physical and psychologic dependence is rare​

Abrupt withdrawal of antipsychotics can precipitate a mild abstinence syndrome

Question 20

FGA drug interactions

Answer 20

Anticholinergic drugs​
Intensify the anticholinergic effect​

CNS depressants​
Can intensify the depressant effect​

Levodopa and direct dopamine receptor agonists​
May counteract the antipsychotic effects of neuroleptics

Question 21

FGA toxicity

Answer 21

Conventional antipsychotic drugs are very safe​

Death by overdose is extremely rare​

Overdose produces hypertension, CNS depression, and EPS​

Treatment​
Intravenous fluids, alpha-adrenergic agonists, and gastric lavage​
Emetics not effective: Neuroleptics block the antiemetic action

Question 22

high potency agents: haloperidol (Haldol)

Answer 22

Butyrophenone family​

Principal indications: Schizophrenia and acute psychosis​

Preferred agent for Tourette syndrome​

Adverse effects​:
Extrapyramidal reactions ​
Neuroendocrine effects​
Can prolong the QT interval and cause dysrhythmias​

​

Question 23

high potency agents: Fluphenazine

Answer 23

Piperazine subclass of phenothiazines​

Principal indications: Schizophrenia and other psychiatric disorders​

Adverse effects​:
Early EPS​
Acute dystonia​
Parkinsonism​
Akathisia​
Sedation, orthostatic hypotension, anticholinergic effects, gynecomastia, galactorrhea, and menstrual irregularities ​

Question 24

low potency agents: chlorpromazine

Answer 24

Therapeutic uses: Schizophrenia, schizoaffective disorder, and the manic phase of bipolar disorder​

Other uses: Suppression of emesis, relief of intractable hiccups, and control of severe behavioral problems in children​

Adverse effects: Sedation, orthostatic hypotension, and anticholinergic effects (e.g., dry mouth, blurred vision, urinary retention, photophobia, constipation, and tachycardia)

Drug interactions: Intensifies responses to CNS depressants (e.g., antihistamines, benzodiazepines, and barbiturates) and anticholinergic drugs (e.g., antihistamines, tricyclic antidepressants, and atropine-like drugs)

Question 25

low potency agent: therioridazine

Answer 25

Prolongs the QT interval and can cause fatal cardiac dysrhythmias​ Reserved for treating schizophrenia in patients who have not responded to safer agents​ Most common adverse effects: Sedation, orthostatic hypotension, anticholinergic effects, and weight gain​

Question 26

atypical antipsychotic agents

Answer 26

Introduced during the 1990s​ Less risk of EPS than FGAs​ Increased risk of weight gain, diabetes, and dyslipidemia

Question 27

clozapine

Answer 27

Mechanism of action​: Blocks dopamine and serotonin​ Therapeutic use​: Schizophrenia​ Levodopa-induced psychosis atypical

Question 28

clozapine ADRS

Answer 28

Agranulocytosis​ Seizures​ Extrapyramidal symptoms​ Diabetes​ Dyslipidemia ​ Weight gain​ Myocarditis​ Effects in older adult patients with dementia​ About double the mortality rate

Question 29

risperidone (risperdal)

Answer 29

atypical Mechanism of action​ Binds to multiple receptors​ Adverse effects​ Generally infrequent and mild​ Preparations, dosage, and administration​ Schizophrenia, oral therapy​ Schizophrenia, intramuscular therapy​ Bipolar disorder

Question 30

paliperidone

Answer 30

Approved for the acute therapy of schizoaffective disorder and for the acute and maintenance therapy of schizophrenia​ Active metabolite of risperidone (9-hydroxy-risperidone) with the same adverse and therapeutic effects as for risperidone itself​ Dosed once a day​ Can prolong QT interval atypical

Question 31

olanzapine (zyprexa)

Answer 31

Approved for schizophrenia, maintenance therapy of bipolar disorder, acute agitation associated with schizophrenia and bipolar mania, and treatment-resistant major depression (in combination with fluoxetine)​ Adverse effects: Carries a low risk of EPS but a high risk of metabolic effects atypical

Question 32

ziprasidone (geodon)

Answer 32

SGA indicated for schizophrenia and acute bipolar mania​ Mechanism of action​ Blocks multiple receptors: dopamine2, 5-hydroxytryptamine2, and histamine1​ Adverse effects: Generally well tolerated ​ Most common side effects: Somnolence, orthostatic hypotension, and rash

Question 33

Quetiapine [Seroquel]

Answer 33

atypical SGA indicated for schizophrenia, major depression, and acute episodes of mania and depression in patients with bipolar disorder​ Adverse effects: Moderate risk of serious metabolic effects, cataracts, and prolonged QT interval​ Drug interactions -multiple

Question 34

Aripiprazole [Abilify]

Answer 34

atypical Dopamine system stabilizers​ Indications: Schizophrenia, acute bipolar mania, major depressive disorder, agitation associated with schizophrenia or bipolar mania, and irritability associated with autism spectrum disorder​ Adverse effects: Headache, agitation, nervousness, anxiety, insomnia, nausea, vomiting, dizziness, and somnolence​

Question 35

Asenapine [Saphris]

Answer 35

Indications: Acute and maintenance therapy of schizophrenia in adults and acute monotherapy or acute adjunctive therapy (with lithium or valproate) of manic or mixed manic episodes associated with bipolar disorder ​ Adverse effects: Drowsiness, hypotension, and prolonged QT interval

Question 36

Iloperidone [Fanapt]

Answer 36

atypical Efficacy equal to that of risperidone and haloperidol​ Better tolerated than some other SGAs​ Still carries a significant risk of weight gain, hypotension, and QT effects

Question 37

depot prep

Answer 37

Depot antipsychotics: Long-acting, injectable formulations used for the long-term maintenance therapy of schizophrenia​ No evidence that depot preparations pose an increased risk of side effects

Question 38

3 major objectives for schizo drug therapy

Answer 38

Suppression of acute episodes​ Prevention of acute exacerbations​ Maintenance of the highest possible level of functioning

Question 39

schizo drug therapy route

Answer 39

Oral (tablets, capsules, and liquids)​ -preferred inhaled -Loxapine [Adasuve] Intramuscular

Question 40

FGA vs SGA

Answer 40

Most FGAs and SGAs are equally effective, except for clozapine, which is more effective than the rest​ FGAs: Significant risk of EPS​ SGAs: Risk of metabolic effects​ FGAs: Cost less than SGAs

Question 41

schizo dosing

Answer 41

Highly individualized​ Older adult patients require relatively small doses​ Size and timing of dose likely to be changed over course of therapy

Question 42

schzio drug therapy

Answer 42

Initial therapy​ Maintenance therapy​ Adjunctive drugs​ Benzodiazepines​ Antidepressants

Question 43

schizo promoting adherence

Answer 43

Ensure that the medication is taken​ Encourage family members to oversee medication for outpatients​ Provide patients with instructions​ Inform patients and their families that antipsychotics must be taken on a regular schedule Inform patients about side effects of treatment​ Assure patients that antipsychotic drug use does not lead to addiction​ Establish a good therapeutic relationship with patient​ Use an intramuscular depot preparation for long-term therapy

Question 44

schizo non drug therapy

Answer 44

Counseling for the patient and family​ Behavioral therapy​ Vocational training