Schizopc Treatment

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  • 1. Schizophrenia and Antipsychotic Treatment Stacy Weinberg 3 April 2007
  • 2. What is it? •It is a severe, chronic, disabling brain disease •Considered to have biological origins but exact unknown •1% of population affected •“Schizophrenia” – split mind ● Multiple personality disorder is not schizophrenia •Psychosis is more accurate ● Severe mental illness where patient loses contact with reality ● People have problems thinking and feeling but are aware of their surroundings
  • 3. Types 1. Catatonic Type • Either in position or speech (imitating others) • Very rare 2. Disorganized Type • Disturbance in behavior, speech, and thought • Flat affect, eccentric 3. Paranoid Type • Delusions and auditory hallucinations • Cognitive functioning remains intact 4. Residual Type • Have been previously diagnosed but no longer show prominent symptoms; still have other symptoms 5. Undifferentiated Type
  • 4. Positive Symptoms • Disturbances of thought processes • Delusions • Hallucinations • Erratic/extreme emotions • Very slow or fast movement, catatonia • Behavioral changes
  • 5. Negative Symptoms • Lack of interest/enjoyment in activities • Low energy/motivation • Blank facial expression, less facial variability • Inability to make or keep friends • Difficulty initiating activities • Social isolation
  • 6. Causes - Dopamine Hypothesis • Genetic aspect • Most think it involves dopamine: – Elevation of D2 monomers, decrease of dimers – Increased release of dopamine • 2x higher • When given amphetamine, 2x more dopamine is released than control
  • 7. Other Hypotheses • Dopamine hypothesis not agreed on by everyone • Some think excitatory amino acids like glutamate could play a role – One type of glutamate receptor, NMDA: NMDA antagonists (ex ketamine) can induce psychotic symptoms in non-schizophrenic patients – Found increase of NMDA receptors in postmortem studies of schizophrenic brains
  • 8. Types of Drug Treatment 1. Typical Antipsychotics • Dopamine antagonists 2. Atypical Antipsychotics • 5-hydroxytryptamine effect, also effect dopamine 3. Combination Drugs
  • 9. Typical • Tend to produce Extrapyramidal side effects: – Parkinsonism – tremors, rigidity, slowness of movement, temporary paralysis – Dystonia – involuntary muscle contractions – Akathisia – inability to resist urge to move – Tardive dyskinesia – involuntary movements of the mouth, lips, and tongue • Chewing, puckering, grimacing, etc.
  • 10. Typical - Phenothiazines • Dopamine D2 receptor antagonists • Chlorpromazine first developed from promethazine, first tricyclic antihistamine Promethazine Chlorpromazine Trifluoperazine
  • 11. Haloperidol • Butyrophenone • Used in 1970s almost exclusively • No anticholinergic effects – therefore used in patients with delirium
  • 12. Atypicals • Atypicals do not induce EPSE • Block D2 receptors and 5-HT seratonin receptors (decreases EPSE) • As opposed to typicals, these are more loosely bound to D2 receptors – Easier dissociation – Shown that higher occupation of D2 receptors by drug, higher incidence of EPSE
  • 13. 5-HT seratonin receptors • Blocking 5-HT seratonin receptors decreases negative symptoms and EPSE – Mechanism is unknown – Seratonin inhibits dopamine release – Positive symptoms associated with hyperdopaminergic condition in limbic lobe – more D2 receptors here, so D2 blocking prevails – Negative symptoms associated with hypodopaminergic condition in frontal lobe – more 5- HT receptors here, so seratonin inhibits dopamine release – stabilizes dopamine level
  • 14. Clozapine • First atypical (1990) • Most dangerous atypical: risk of agranulocytosis (severe decrease in WBC count) • Most effective in reducing EPSE, also in reducing negative symptoms – Increases Fos-positive neurons in the prefrontal cortex (shown to affect negative symptoms)
  • 15. Risperidone • Low doses needed • Predominantly blocks D2, then 5-HT – Does not exhibit multireceptor action • Lacks anticholinergic activity – makes it better for youth, elderly • Problem – increases prolactin levels (shouldn’t give to people with breast cancer)
  • 16. Olanzapine • Zyprexa is number one antipsychotic in sales (Eli Lilly) • Exhibits multireceptor action • Good for controlling mood symptoms • Available in a wafer • Problems: Sedation and weight gain
  • 17. Combinations • Example is Symbyax – Combination of olanzapine and fluoxetine (Prozac) – Can also treat bipolar disorder • Combination of ziprasidone and clozapine – Can be used to combat treatment resistance • Combination of aripriprazole and clozapine