The Treatment of Psychotic Disorders By Siva Dantu
The Treatment of Psychotic Disorders By: Siva Dantu
What is Psychosis • “ a loss of contact with reality, usually including false beliefs about what is taking place or who one is (delusions) and seeing or hearing things that aren’t there (hallucinations) • Treated with anti-psychotics
Disorders with Psychosis • • • Bipolar Disorder Schizoaffective Disorder Schizophrenic Disorder Depression Personality Disorders • Schizotypal • Schizoid • Paranoid
Bipolar Disorder
Bipolar Disorder cont. Two main different types: • Bipolar I • Manic around 1 week • Depressive around 2 weeks • Bipolar II • Depressive • Hypomanic Treatments: Mood Stabilizers: - Lithium Antipsychotics
Schizophrenia • What is Schizophrenia? • http: //www. youtube. com/watch? v=bih 7 RTB 9 u 04
Schizophrenia cont. Symptoms: • Delusions • Hallucinations • Disorganized speech and behavior • Negative Symptoms • Blunted affect • Alogia • Avolition
Schizophrenia cont. • Delusions • • Religious Persecutory Grandiose Control • Instertion • Withdrawal • Broadcasting Hallucinations - Visual - Auditory - Olfactory - Tactile
Schizoaffective Disorder • Spectrum • The differences between Schizoaffective and… • Schizophrenia • Bipolar Disorder
Schizoaffective Disorder cont. • Treatment: • Mood Stabilizers • Antipsychotics • http: //www. youtube. com/watch? v=htw. AXZw_gk. A
Psychotic Disorders • Hereditary? • Substance Induced? • PCP • Cocaine • Cannabis
Antipsychotics Or neuroleptics
Chlorpromazine History - Was the first antipsychotic used - Around 1952 - French doctor - Revolutionary - Only existed electroconvulsive therapy and psychotherapy - Used in anesthesia - Sedative effects
Antipsychotics: Chlorpromazine cont.
Chlorpromazine • Mechanism of Action - Dopamine - EPS - Histamine - Weight gain - Sedative effect - Alpha 1 adrenergic - orthostatic hypotension
EPS: extrapyramidal symptoms • Dystonias • Involuntary convulsion of muscles • Development of Parkinson’s syndrome • Dyskinesias • Involuntary body of facial movements • 20% eventually developed
Phenothiazine-Derived Drugs • All are derivatives from the phenothiazine tricyclic compound • 3 different classes • Aliphatic • Piperidines • Piperazines
Aliphatic Phenothiazines Chlorpromazine Promazine Triflupromazine
Piperidine Phenothiazines Mesoridazine Thioridazine
Piperazine Phenothiazines Fluphenazine Perphenazine
Butyrophenones Haloperidol Benperidol
Problems with Typical Antipsychotics • Solves no negative symptoms • EPS are very troublesome • Glutamatergic vs. Dopaminergic
Discovery of Clozapine • History • Comparison study of angles between anti-depressants and psychotics • The group found clozapine. Consequently didn’t work with theory • In clinical trails Clozapine didn’t exhibit EPS • Also solved many negative symptoms
Clozapine cont. • Slow acceptance • Precaution • Agranulocytosis
Clozapine Mechanism of Action • Weaker D 2 receptor binding • Stronger serotonin antagonist • Postsynaptic 5 -HT 2 receptors JUST LIKE CHLORPROMAZINE BECAME A MODEL OF ATYPICAL ANTIPSYCHOTICS TODAY
Other atypical antipsychotics Risperadome – less harmful , weaker affinity for D 2
Other atypical antipsychotics cont. Olanzapine- much less is needed 100 fold stronger antagonist alpha 2 andrenergic
Third Generation Antipsychotics • Aripiprazole (Abilify) • Partial agonist • Partial 5 HT 1 receptor
References http: //en. wikipedia. org/wiki/Antipsychotic http: //www. nlm. nih. gov/medlineplus/ency/article/001553. html http: //www. nimh. nih. gov/health/topics/schizophrenia/index. shtml http: //www. mayoclinic. com/health/schizoaffective-disorder/DS 00866 http: //www. nimh. nih. gov/health/publications/bipolardisorder/complete-index. shtml Hippius, H. (1989). The History of clozapine. Psychopharmacology, 99, S 3 -S 5. Leonard, B. (2003). Fundamentals of psychopharmacology. Chichester, England: John Wiley & Sons Ltd. Meyer, J, & Simpson, G. (1997). From Chlorpromazine to olanzapine: a brief history of antipsychotics. Psychopharmacology, 48(9), 1137 -1139. Shen, Winston. (1999). A History of antipsychotic drug development. Comprehensive Psychiatry, 40(6), 407 -414.
Required Reading Goodman and Gilman’s Pharmacological Basis of Therapeutics, Chapter 18, pp. 461 -467.
Questions 1. What are the biggest differences that separate a typical from an atypical antipsychotic? 2. Why isn’t clozapine in the medical market today? 3. Draw one drug from each of the three different types of phenothiazines and point out what makes each structurally different. 4. What is the main receptor that had been related to psychosis and discuss how this idea is changing.
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