Watts Schizo Flashcards
Etiology of schizophrenia
-Neurodevelopmental/anatomical
-Genetics-neuronal growth, migration of neurons
-Environmental-birth complications, infections
-Gene-environment interaction
-Neurodevelopment-environment interaction
What are positive symptoms of schizophrenia?
-Respond well to drug therapy
-Hallucinations
-Delusions
-Bizarre behavior
-Thought disorder
What are negative symptoms of schizophrenia?
-Little response to drug therapy, newer agents are better
-Blunted emotion
-Poor self-care
-Social withdrawal
-Poverty in speech
What are the receptors antagonized by antipsychotics?
-Dopamine
-Serotonin
-Norepinephrine
-Acetylcholine
-Histamine
What is the major receptor antagonized by antipsychotics?
Dopamine
What is the newer receptor antagonized by antipsychotics?
Serotonin
What has more predictable dosing, D2 or D1?
D2
Actions of D2 antagonists on the basal ganglia (nigrostriatal pathway)
-Motor effects
-Extrapyramidal symptoms
Actions of D2 antagonists on the mesolimbic
Primary therapeutic effects
Actions of D2 antagonists on the mesocortical
-Hypofunction in schizophrenia
-Antagonists may exacerbate cognitive deficits
Actions of D2 antagonists on the Hypothalamus and endocrine systems
D2 receptor blockade in endocrine system
Actions of D2 antagonists on the medulla
-Chemoreceptor trigger zone
-D2 antagonists are anti-emetics
Drug-induced movement disorders (D2 antagonism)
-Extrapyramidal symptoms (EPS) (30-50%)
-Tardive dyskinesia (20-40%)
-Neuroleptic malignant syndrome (NMS)
When do extrapyramidal symptoms appear?
Occur early, days/weeks, reversible
What are the extrapyramidal symptoms?
-Dystonia - increased muscle tone
-Pseudoparkinsonism - muscle rigidity
-Tremor
-Akathisia - restlessness
Drug therapy for EPS
-Anticholinergic agents
-Antihistamines
-Dopamine-releasing agents
-Used for akathisia
When does tardive dyskinesia appear
Occur late, months to a year, IRREVERSIBLE
Symptoms of tardive dyskinesia
-Mouth - rhythmic involuntary movements
-Choreiform - irregular purposelessness
-Athetoid - worm-like
-Axial hyperkinesias - “to-and-fro” movements
Monitoring of tardive dyskinesia
AIMS (abnormal involuntary movement scale) rating scale; check every 6 months
Treatment of tardive dyskinesia
-Prevention! Use the least risky agent at the lowest dose possible and monitor
-Reduce dose of current agent
-Change to a different drug; possibly a newer agent
-Eliminate anticholinergic drugs
-VMAT inhibitors
What are the VMAT inhibitors for tardive dyskinesia
-Tetrabenazine (Xenazine) for Huntington’s chorea
-Valbenazine (Ingrezza) for TD
-Deutetrabenazine (Austedo) for TD and Huntington’s chorea
When does neuroleptic malignant syndrome appear?
Immediately and serious; 10% fatality
What are the symptoms of neuroleptic malignant syndrome?
-EPS symptoms with fever
-Impaired cognition - agitation, delirium, coma
-Muscle rigidity
Treatment of neuroleptic malignant syndrome
-Restore dopamine balance
-Discontinue drug
-DA agonists, diazepam, or dantrolene (skeletal muscle relaxant)
How long does it take for antipsychotic drugs to take effect when treating psychosis?
-2-3 weeks for effectiveness
-6 weeks to 6 months maximal efficacy
Pharmacological effects of the antipsychotic drugs
-Behavioral effects: Unpleasant in normal subjects or reversal of signs and symptoms of psychosis in affected individual
-“Neuroleptic” syndrome: Suppress emotions, reduce initiative and interest, affect; may resemble negative symptoms
-Block conditioned avoidance responses in animal studies
-Decreased spontaneous activity, aggressive, and impulsive behavior
Manifestations associated with muscarinic cholinoreceptor blockade
-Loss of accommodation
-Dry mouth
-Difficulty urinating
-Constipation
Manifestations associated with alpha adrenoreceptor blockade
-Orthostatic hypotension
-Impotence
-Failure to ejaculate
Manifestations associated with dopamine receptor blockade
-Parkinson’s syndrome
-Akathisia
-Dystonias
Manifestations associated with supersensitivity of dopamine receptors
Tardive dyskinesia
Manifestations associated with muscarinic blockade
Toxic-confusional state
Manifestations associated with histamine receptor blockade
Sedation
Manifestations associated with dopamine receptor blockade resulting in hyperprolactinemia
-Amenorrhea-galactorrhea
-Infertility
-Impotence
Manifestations associated with combined histamine and serotonin blockade
Weight gain
Precautions/contraindications associated with antipsychotic drugs
-Cardiovascular (hypotension and QT interval prolongation)
-Parkinsons disease
-Epilepsy (clozapine will lower seizure threshold)
-Diabetes (contraindicated for newer agents)
What does a drug that has high serotonin/dopamine ratio cause?
EPS
What are the aliphatic phenothiazines?
-Chlorpromazine (Thorazine) - no longer first-line therapy
-Promethazine (Phenergan) - more likely to be used for N/V
Which aliphatic phenothiazine is more likely to be used for H1 antagonist properties?
Promethazine
What are the piperidine phenothiazines?
Thioridazine (Mellaril) - sedation, hypotension; anticholinergic, many SE
What are the piperazine phenothiazines?
-Fluphenazine (Permtil, Prolixin) - EPS
-Prochlorperazine (Compazine) - antiemetic
-Perphenazine (Trilafon) - just as effective as newer agents
What are the thioxanthines?
-Thiothizene (Navane) - modest EPS
What are the butyrophenones?
-Haloperidol (Haldol) - EPS
Miscellaneous antipsychotics
-Molindone (Moban) - moderate EPS
-Pimozide (Orap) - Tourette’s disease-tics, vocalizations
Key points of chlorpromazine (Thorazine)
-First antipsychotic
-Antihistamine side effects
Key points of promethazine (Phenergan)
-Antihistamine
-Antiemetic
Key points of thioridazine (Mellaril)
-Many side effects: anticholinergic, sexual dysfunction, cardiovascular
Key points of perphenazine (Trilafon)
CATIE studies: combination with anticholinergic
Key points of thiothixene (Navane)
Modest EPS
Key points of haloperidol (Haldol)
EPS
Key points of molindone (Moban)
Moderate EPS
Key points of pimozide (Orap)
Tourette’s disease, suppress motor and vocal tics
Atypical/second generation antipsychotics
-Clozapine
-Olanzapine
-Loxapine
-Quetiapine
-Risperidone
-Paliperidone
-Iloperidone
-Ziprasidone
-Asenapine
-Lurasidone
-Pimavanserin
-Aripiprazole
D2/D3 partial agonists
-Brexpiprazole
-Cariprazine
-Lumateperone
Clozapine key points
-First atypical antipsychotic
-Agranulocytosis
-Risk of diabetes
-Superior efficacy
Olanzapine key points
-Weight gain
-Risk of diabetes
Quetiapine key points
-Metabolite with antidepressant activity
-Hypotension
-Sedation
Risperidone key points
-Serotonin/dopamine receptor antagonist
Ziprasidone key points
-Serotonin/dopamine, alpha 1 affinity
-prolongs QT interval
Lurasidone key points
-Serotonin/dopamine receptor affinity
-Reduced metabolic effects
-Rapid titration
Aripiprazole key points
-High serotonin/dopamine receptor affinity
-Partial agonist activity
Drugs in development/under investigation
Dual M1/M4 muscarinic agonist combined with peripheral muscarinic antagonist (KarXT)
