atypical antipsychotic clozapine by: patrizia orlando

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  • Slide 1
  • ATYPICAL ANTIPSYCHOTIC CLOZAPINE BY: PATRIZIA ORLANDO
  • Slide 2
  • CLOZAPINE Clozapine is a second generation/atypical antipsychotic. Clozapine is a second generation/atypical antipsychotic. Trade name is Clozaril Trade name is Clozaril
  • Slide 3
  • HISTORY OF ANTIPSYCHOTICS Anti-psychotics were discovered accidentally by a French naval surgeon, Henri Laborit. Laborit was interested in circulatory shock, not schizophrenia. Anti-psychotics were discovered accidentally by a French naval surgeon, Henri Laborit. Laborit was interested in circulatory shock, not schizophrenia. Laborit experimented with a variety of drugs to combat shock syndrome. Laborit experimented with a variety of drugs to combat shock syndrome. One of the drugs was an agent called Pomethazine. His primary reason for using the drug was for its effects on the ANS, however, he discovered the secondary properties of the drug One of the drugs was an agent called Pomethazine. His primary reason for using the drug was for its effects on the ANS, however, he discovered the secondary properties of the drug The drug made patients drowsy, reduced pain, and created a feeling of euphoric quietude. This drug has psychological effects. The drug made patients drowsy, reduced pain, and created a feeling of euphoric quietude. This drug has psychological effects. Laborits observation were used to modify the formula of Promethazine into the first effective anti-psychotic medication, Chloropromazine (Thorazine). Laborits observation were used to modify the formula of Promethazine into the first effective anti-psychotic medication, Chloropromazine (Thorazine). Heinrichs, R. W., (2001). In Search of Madness: Schizophrenia and Neuroscience. Oxford University Press: New York. Heinrichs, R. W., (2001). In Search of Madness: Schizophrenia and Neuroscience. Oxford University Press: New York.
  • Slide 4
  • Side Effects of Typical Antipsychotics Extrapyramidal Symptoms (EPS): Typical antipsychotics effect the extrapyramidal tract by blocking post-synaptic receptors in the basal ganglia. Chief among the acute side effects are motor disturbances, which gives the appearance of Parkinsonism. Extrapyramidal Symptoms (EPS): Typical antipsychotics effect the extrapyramidal tract by blocking post-synaptic receptors in the basal ganglia. Chief among the acute side effects are motor disturbances, which gives the appearance of Parkinsonism. Dyskinesia: disordered movements Dyskinesia: disordered movements Akinesia: slowness of movement and underactivity Akinesia: slowness of movement and underactivity Tardive Dyskinesia: repetative unvoluntary movement of the mouth and tongue ( often in the form of a lip smacking), trunk, and extremities. Tardive Dyskinesia: repetative unvoluntary movement of the mouth and tongue ( often in the form of a lip smacking), trunk, and extremities. (30-50% of patients experience these side effects while on typical antipsychotic medication.) (30-50% of patients experience these side effects while on typical antipsychotic medication.) Negative Symptoms: typical antipsychotics seemed to have little to no improvement in negative symptoms. Negative Symptoms: typical antipsychotics seemed to have little to no improvement in negative symptoms.
  • Slide 5
  • ARRIVAL OF THE ATYPICAL ANTIPSYCHOTIC German psychiatrists working with G. Stille at Wander Pharmaceuticals in Bern, Switzerland, in the early 1960s worked to refute that EPS and antipsychotic efficacy were linked. Their work led to the introduction of Clozapine, an antipsychotic with no EPS. German psychiatrists working with G. Stille at Wander Pharmaceuticals in Bern, Switzerland, in the early 1960s worked to refute that EPS and antipsychotic efficacy were linked. Their work led to the introduction of Clozapine, an antipsychotic with no EPS. Clozapine was briefly marketed and quickly withdrawn for two reasons: Clozapine was briefly marketed and quickly withdrawn for two reasons: The embarrassment of not having any EPS, and The embarrassment of not having any EPS, and Agranulocytosis Agranulocytosis
  • Slide 6
  • Side Effects of Clozapine Major side effect: Major side effect: Agranulocytosis: a destructive condition in which the bone marrow stops producing white blood cell, thus making the patient susceptible to infection. Agranulocytosis: a destructive condition in which the bone marrow stops producing white blood cell, thus making the patient susceptible to infection. Clozapine may cause many side effects. The following side effects are grouped by the body system affected: Clozapine may cause many side effects. The following side effects are grouped by the body system affected: Cardiovascular: decreases of blood pressure which may cause dizziness or fainting; rapid heart rate, changes in heart rhythm and electrocardiogram. Cardiovascular: decreases of blood pressure which may cause dizziness or fainting; rapid heart rate, changes in heart rhythm and electrocardiogram. Nervous system: sedation, increased seizure tendency. Nervous system: sedation, increased seizure tendency. Digestive system: increased appetite (weight gain), excessive salivation, nausea, constipation, abnormal liver tests, elevated blood sugar. Digestive system: increased appetite (weight gain), excessive salivation, nausea, constipation, abnormal liver tests, elevated blood sugar. Autonomic: blurred vision, exacerbation of glaucoma, dry mouth, nasal congestion, decreased sweating Autonomic: blurred vision, exacerbation of glaucoma, dry mouth, nasal congestion, decreased sweating Skin: rashes Skin: rashes http://www.minddisorders.com/Br-Del/Clozapine.html http://www.minddisorders.com/Br-Del/Clozapine.html
  • Slide 7
  • STUDY 1 A Double-Blind Comparative Study of Clozapine and Risperidone in the Management of Severe Chronic Schizophrenia By: Azorin, J. M. et al. Type of study: Double-blind comparative study Type of study: Double-blind comparative study Population: Male and female patients aged 18-65 years who met the DSM-IV criteria for schizophrenia and study requirements for poor previous treatment response. Population: Male and female patients aged 18-65 years who met the DSM-IV criteria for schizophrenia and study requirements for poor previous treatment response. Patients:Total of 273 patients were randomly assigned to one of the two groups, and 201 patients completed the study. Reasons for leaving the study included adverse event, consent withdrawal, protocol violation, treatment failure, and death (unrelated to therapy). Patients:Total of 273 patients were randomly assigned to one of the two groups, and 201 patients completed the study. Reasons for leaving the study included adverse event, consent withdrawal, protocol violation, treatment failure, and death (unrelated to therapy). Results: Results: Magnitude of the response (determined by BPRS and CGI scores) was significantly greater in the Clozapine group. Magnitude of the response (determined by BPRS and CGI scores) was significantly greater in the Clozapine group. Clozapine exhibited clear therapeutic superiority over Risperidone for the majority of the efficacy measures. Clozapine exhibited clear therapeutic superiority over Risperidone for the majority of the efficacy measures. Limitations: Limitations: Significant difference in the dosage amount between the groups which could exert some explanation for the difference in efficacy. Significant difference in the dosage amount between the groups which could exert some explanation for the difference in efficacy.
  • Slide 8
  • STUDY 2 Positive and Negative Symptom Response to Clozapine in Schizophrenic Patients With and Without the Deficit Syndrome By: Buchanan, R. W. et al. Type of study: 10 week Double-blind, parallel-groups comparison of Clozapine and Haloperidol Type of study: 10 week Double-blind, parallel-groups comparison of Clozapine and Haloperidol Population: Male and female patients that meet the DSM-III-R criteria for schizophrenia or schizoaffective disorder who also had residual (+) and (-) symptoms after previous treatment. Population: Male and female patients that meet the DSM-III-R criteria for schizophrenia or schizoaffective disorder who also had residual (+) and (-) symptoms after previous treatment. Patients: 64 of the 75 patients completed the study. Reasons for drop out was for noncompliance, relapse, and low RBC count, seizures, and withdrawal of consent. Patients: 64 of the 75 patients completed the study. Reasons for drop out was for noncompliance, relapse, and low RBC count, seizures, and withdrawal of consent. Results: Results: For patients that completed the 10 week double blind study, Clozapine was superior to Haloperidol in treating positive symptoms, however, there was no long term effect of Clozapine on primary or secondary negative symptoms. For patients that completed the 10 week double blind study, Clozapine was superior to Haloperidol in treating positive symptoms, however, there was no long term effect of Clozapine on primary or secondary negative symptoms. Patients receiving Haloperidol worsened in Anhedonia significantly. Patients receiving Haloperidol worsened in Anhedonia significantly. Limitations Limitations Patients used were not limited solely to those diagnosed with schizophrenia Patients used were not limited solely to those diagnosed with schizophrenia Sample size was small Sample size was small
  • Slide 9
  • STUDY 3 The safety of clozapine in the treatment of first- and multiple-episode patients with treatment-resistant schizophrenia By: Hofer, A. et al. Population: Population: Contrasted first and multiple episode male and female patients with schizophrenia on Clozapine. Contrasted first and multiple episode male a

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