Chapter 26: Antipsychotics -use in Schitzophrenia Flashcards
antipsychotic agents
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
FGA
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)
SGA
Second-generation antipsychotics (SGAs) or atypical antipsychotics
Produce only the moderate blockade of dopamine receptors; stronger blockade for serotonin
Fewer EPS
schitzo clinical presentation
Disordered thinking and reduced ability to comprehend reality
Three types of symptoms
positive schitzo s/sx
Exaggeration or distortion of normal function
Hallucinations
Delusions
Agitation
Tension
Paranoia
neg schitzo s/sx
Loss or diminution of normal function
Lack of motivation
Poverty of speech
Blunted affect
Poor self-care
Social withdrawal
cognitive schitzo s/sx
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
schizo clinical presentation: acute episodes
Delusions (fixed false beliefs) and hallucinations are frequently prominent
schizo clincal presentation: residual s/sx
Suspiciousness; poor anxiety management; and diminished judgment, insight, motivation, and capacity for self-care
schizo long-term course
Acute exacerbations separated by intervals of partial remission
etiology of schizo
Genetic
Perinatal
Neurodevelopmental
Neuroanatomic factors
Excessive activation of CNS receptors for dopamine
Insufficient activation of CNS receptors for glutamate
FGA classification
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
FGA MOA
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
FGA therapeutic actions
Schizophrenia is the primary indication for antipsychotic drugs
These drugs suppress symptoms during acute psychotic episodes
Continued use reduces the risk of relapse
FGA ADR: EPS
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
FGA ADR: NMS
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
nms TX
Supportive measures
Drug therapy: Dantrolene and bromocriptine
Immediate withdrawal of antipsychotic medication
FGA ADR: other
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
FGA physical and psychologic dependence
Development of physical and psychologic dependence is rare
Abrupt withdrawal of antipsychotics can precipitate a mild abstinence syndrome
FGA drug interactions
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
FGA toxicity
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
high potency agents: haloperidol (Haldol)
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
high potency agents: Fluphenazine
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
low potency agents: chlorpromazine
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)
low potency agent: therioridazine
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
atypical antipsychotic agents
Introduced during the 1990s
Less risk of EPS than FGAs
Increased risk of weight gain, diabetes, and dyslipidemia
clozapine
Mechanism of action:
Blocks dopamine and serotonin
Therapeutic use:
Schizophrenia
Levodopa-induced psychosis
atypical
clozapine ADRS
Agranulocytosis
Seizures
Extrapyramidal symptoms
Diabetes
Dyslipidemia
Weight gain
Myocarditis
Effects in older adult patients with dementia
About double the mortality rate
risperidone (risperdal)
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
paliperidone
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
olanzapine (zyprexa)
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
ziprasidone (geodon)
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
Quetiapine [Seroquel]
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
Aripiprazole [Abilify]
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
Asenapine [Saphris]
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
Iloperidone [Fanapt]
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
depot prep
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
3 major objectives for schizo drug therapy
Suppression of acute episodes
Prevention of acute exacerbations
Maintenance of the highest possible level of functioning
schizo drug therapy route
Oral (tablets, capsules, and liquids) -preferred
inhaled -Loxapine [Adasuve]
Intramuscular
FGA vs SGA
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
schizo dosing
Highly individualized
Older adult patients require relatively small doses
Size and timing of dose likely to be changed over course of therapy
schzio drug therapy
Initial therapy
Maintenance therapy
Adjunctive drugs
Benzodiazepines
Antidepressants
schizo promoting adherence
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
schizo non drug therapy
Counseling for the patient and family
Behavioral therapy
Vocational training
