antipsychotic drugs

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ghrelin23187
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226020
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antipsychotic drugs
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2013-07-05 13:41:39
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  1. Mood-altering drugs
    -10-20% of all prescriptions in US

    ANTIPSYCHOTICS  (severe psychiatric illnesses)

    ANTIDEPRESSANTS  (mood elevators)

    LITHIUM SALTS  (mood stabilizers)

    ANXIOLYTICS  (most are sedatives)
  2. Antipsychotics Common Indications
    • Schizophrenia
    • Schizoaffective   disorder
    • Mood Disorder with psychosis
    • Dementia with psychosis
    • Delirium
    • Delusional disorder
    • Psychosis secondary to a non-psychiatric medical disorder 
    • Developmental disability with psychosis and/or aggression
    • Tourette’s disorder, Huntington’s ,chorea, intractable hiccups
    • Acute Mania
    • Augmentation in Major Depression and Bipolar disorder
  3. PSYCHOSIS
    • severely disordered thought and emotion
    • 2 kinds
    • --organic: memory and orientation are affected
    • --Idiopathic: memory and orientation are intact (schizophrenia)
  4. Schizophrenia --symptom
    •Positive Symptoms: Hallucinations, Delusions

    •Negative Symptoms: Blunted affect, Anhedonia, Social withdrawal, Avolition, Alogia

  5. Schizophrenia -- epidemiology
    Lifetime prevalence: 1%

    Age of onset: 18-35 (mean=20)
  6. Antipsychotic Drugs
    Typical Antipsychotics (neuroleptics): block postsynaptic D2 dopamine receptors

    Efficacy?: reduce positive symptoms
  7. Dopamine hypothesis
    • •Schizophrenia
    • – caused by excessive amounts of dopamine

    • •Problems?
    • –Typical antipsychotics are unable to
    • reduce negative symptoms

    • •Conclusions
    • –Dopamine is undeniably involved
    • –However, mechanism of Schizophrenia is
    • much more complex (e.g. structural changes)
  8. Structural changes in Schizophrenia
    ???
  9. Other Antipsychotic Drugs
    • Atypical Antipsychotics (e.g. clozapine, risperidone)
    • –block 5-HT2A serotonin receptors

    –weakly block D2 receptors

    •Efficacy

    –reduce positive symptoms

    –some are able to mildly attenuate negative symptoms

    •Conclusions

    –further evidence of dopamine involvement

    –evidence that other neurotransmitters are involved
  10. Typical antipsychotic drugs
    (phenothiazines, thioxanthenes, buterophenones)
    • proven clinical efficacy, but all share important side effects. Due to the highly
    • variable therapeutic response and variable tolerance to side effects, treatment
    • is highly individualized, and dosages can differ as high as 20- to 30-fold
    • between patients.
  11. Dopamine Receptor Blockade (effects)
    Antipsychotic effect: dec emotional, display, hallucinations, output of RF in response to sensory stimuli

    Antiemetic effect: at low doses, action on CTZ

    Hypothalamic effect:- loss of thermoregulation, dec cortitropin levels, inc prolactin lvl and appetite, weight gain
  12. Dopamine receptor blockage (extrapyramidal symptoms)
    Early: dystonia, akathisia, parkinsonism, neuroleptic malignant syndrome (rare)

    Late: Perioral tremor, tardive dyskinesia 405)
  13. a-Adrenergic receptor blockade
    •postural hypotension

    •reflex tachycardia

    •pressor effects of epinephrine
  14. Cholinergic receptor blockade
    •suppression of some dyskinesias

    •blurred vision

    •dec salivation, inc incidence of caries

    •constipation
  15. Incidence of tardive dyskinesia as a function of neuroleptic exposure
    inc in incidence with inc in neuroleptic exposure
  16. Incidence of TD with risperidone compared with haloperidol in older patients
    Haloperiol has higher incidence than Risperidone.

    Risperidone's incidence plateau after 3 month of txn
  17. The single most effective means to reduce the occurrence of TD
    is to use novel antipsychotics in preference to conventional neuroleptics
  18. 2nd Generation/Novel/Atypical? Profile
    Diminished extrapyramidal side effects (EPS)

    Minimized risk for tardive  dyskinesia (TD)

    No hyperprolactinemia

    Beneficial for treatment of refractory patients

    Improved negative symptoms

    Improved cognitive/mood symptoms
  19. The Role of Clozapine
    Advantages: txn of refractory pt, negative symptoms, minimal risk of eps or TD, no prolatin inc

    Disadvantage: agranulocytosis, seizures, weight gain, orthostasis, tachycardia, sedation, sialorrhea, constipation
  20. Adverse Effects of Antipsychotics
    Weight gain after 10 weeks
  21. Adverse Effects of Antipsychotics - Anticholinergic
    Most common with:

    Clozapine, Olanzapine, Quetiapine, Low-potency neuroleptics
  22. Adverse Effects of Antipsychotics

    Sexual Adverse Effects
    anti-serotonin (5HT2)

    anti-dopamine (impaired erection, inhibited orgasms)

    anti-norepinephrine (reduced intensity of orgasm)

    anti-cholinergic (impaired erection)

    anti-histamine (loss of libido, impaired erection)
  23. adverse effects with atypicals drugs
    • fewer
    • greatly reduce adverse effects burden
    • Clozapine is an exception
  24. Antipsychotic txn - risk of EPS and TD
    major dec
  25. Antipsychotic txn - prolactin
    inc
  26. Antipsychotic txn - Weight gain
    a problem and varies across atypical class

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