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Prajogo Wibowo
School of Medicine - Hang Tuah University
Schizophrenia
Antipsychotics
Though the disease is not cured by
drug therapy, the symptoms of
schizophrenia, including thought
disorder, emotional withdrawal, and
hallucinations or delusions, may be
attenuated by antipsychotic drugs.
Unfortunately, protracted therapy
(years) is often needed and can result
in severe toxicity in some patients.1
Antipsychotic Classes
Phenothiazones, thioxanthenes, and
butyrophenones
Antipsychotic Classes
Atypically
Heterocyclics (more effective and less
toxic in some cases)
Clozapine [Clozaril]
Onlanzapine [Zyprexa]
Risperidone [Risperdal]
Quetiapine [Seroquel]
Ziprasidone [Geodon]
Etc.
Mechanism of Action
Dopamine hypothesis
Excess of dopamine in specific neural tracts
D2 receptor is in the caudate putamen, nucleus
accumbens, cerebral cortex, and hypothalamus
Mechanism
of Action
Dopamine pathways
Mentation & Mood
Mesocortical
Mesolimbic
Extrapyramidal Function
Nigrostriatal
Prolactin release
Tuberoinfundibular
Emesis
Chemoreceptor trigger zone
3
Mechanism of Action
Other receptors
Desirable Effects
Reduction of positive symptoms
Hyperactivity, bizarre ideation, hallucinations, delusions
Typicals and atypicals reduce positive symptoms
Adverse Effects
Reversible parkinsonism, akathisias, and dystonias
Treatment is to decrease antipsychotic dose or use
muscarinic blocking agents
Less common with atypicals
Tardive dyskinesias
Develop within 6 months to several years of therapy
Antimuscarinics increase TD severity
May be caused by dopamine receptor sensitization because
increasing antipsychotic doses temporarily attenuates
symptoms
May be irreversible
No pharmacological treatment
Adverse Effects
Autonomic effects
Adverse Effects
Sedation
More marked with phenothiazines
Except for sertindole, all atypicals block histamine receptors
Miscellaneous toxicities
Thioridazine retinal deposits causing visual impairments, high
doses leads to fatal ventricular arrhythmias
Sertindole prolonged QT segment leading to arrhythmias
Clozapine 1-2% incidence of agranulocytosis, seizures at high
doses
Overdose toxicity
Other than thioridazine (cardiotoxicity), overdoses are usually
not fatal
Lowers seizure threshold
Hypotension responds to fluid replacement