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Objectives
1. To know the basis for the dopamine hypothesis of schizophrenia 2. To understand the mechanism of action of antipsychotic agents with respect to their therapeutic and adverse effects
Antipsychotics
aka neuroleptics, major tranquilizers
Neuroleptics because of their tendency to cause movement disorders Major tranquilizers vs minor tranquilizers (anxiolytics)
Psychosis
Symptoms of delusions, hallucinations, and disorders of thought
Due to increase dopamine levels (as in amphetamines, cocaine)
Psychosis
Schizophrenia
1% of population, inheritable
Characterized by positive and negative symptoms, a pattern of social and occupational deterioration, and persistence of the illness for at least 6 months
2 or more symptoms
Positive Symptoms
1. Hallucinations - auditory, visual, tactile, and/or olfactory hallucinations, voices that are commenting
2. Delusions - grandiose, paranoid, thought broadcasting, thought insertion
3. Bizarre behavior - aggressive/agitated, odd clothing or appearance, odd social behavior, repetitive-stereotyped behavior
Rogie Royce Z. Carandang, RPh
Negative Symptoms
Adverse Effects
Receptor Blocked Side Effect
Dopamine D2
Histamine H1
Parkinsonism/ EPS
Sedation
Muscarinic M
Adrenergic 1
Chlorpromazine
Phenothiazine Ring
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Haloperidol
Clozapine
Thioridazine (Mellaril, Melleril) Chlorpromazine (Thorazine, Laractyl, Psynor) Perphenazine (Trilafon) Thiothixene (Navane) Fluphenazine (Prolixin, Modezine, Sydepress) Haloperidol (Haldol, Serenace)
Blocks D2 receptors only Treats positive symptoms only Causes movement disorders (Parkinsonism)
Clozapine (Clozaril, Leponex) Quetiapine (Seroquel) Ziprasidone (Geodon, Zeldox) Aripiprazole (Abilify) Olanzapine (Zyprexa) Risperidone (Risperdal)
Blocks 5-HT2 > D2 receptors Treats both positive and negative symptoms Causes little or no movement disorders
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Movement Disorders
1. Extrapyramidal symptoms (EPS) aka neuroleptic-induced parkinsonism Most common (15%) Coarse tremors, rigidity, bradykinesia Risk: high potency Tx: lower dose, anticholinergics (benztropine [Cogentin], diphenhydramine, biperiden [Akineton], trihexyphenydyl [Artane])
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Movement Disorders
2. Acute Dystonia - Muscular spasm, involuntary movement - Spasmodic torticollis, trismus, tongue potrusion, ophisthotonos, upward movement of eyes (oculogyric crisis) - Risk: high potency - Tx: IM/IV anticholinergics
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Movement Disorders
3. Neuroleptic malignant syndrome (NMS) Idiosyncratic, life-threatening Motor: Muscular rigidity, dystonia, agitation Autonomic: hyperpyrexia, hypertension Risk: high dose, rapid dose escalation Tx: discontinue meds, supportive, dantrolene, bromocriptine
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Movement Disorders
4. Akathisia - Subjective feeling of muscular discomfort - Agitated, pace relentlessly, alternately sit and stand - Tx: Beta-blockers (propranolol), BZD (lorazepam), clonidine
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Movement Disorders
5. Tardive dyskinesia - Choreoathethoid movements - Tongue protrusion/twisting, lip puckering - Tx: lower dose, change meds
End of Lecture!
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