Pharmacology Exam 4

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Rx2013
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49268
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Pharmacology Exam 4
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2010-11-13 13:54:55
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Anti psychotic Drugs
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Anti-psychotic Drugs
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  1. A particular kind of psychosis characterized mainly by a clear sensorium but a marked thinking disturbance
    • schizophrenia
    • 1% of population
  2. Support for the Dopamine Hypothesis for Schizophrenia
    • many antipsychotics block postsynaptic D2 receptors in the CNS
    • drugs that increase DA activity aggrivate schiz. or induce psychosis
    • increased DA receptors in schizophrenics
    • successful treatment results in a change in DA metabolites excreted
  3. Theories against the Dopamine Hypothesis for Schizophrenia
    • current antipsychotics are partially effective or ineffective
    • Phencyclidine (NMDA receptor antagonist) induces schiz. more than DA agonsist
    • Atypical anti psychotics are effective in schiz. but are not potent DA blockers
    • DA blockade is fast, but antipsychotics take weeks to work
  4. Serotonin Hypothesis for schizophrenia
    • Hallucinogens are 5-HT agonists
    • Clozapine and quetiapine are inverse agonists of 5-HT2A
    • 5-HT2A/C regulate DA and NMDA neurotransmission
  5. Support for Glutamate hypothesis for schizophrenia
    phencyclidine (NMDA receptor antagonist) induces schizophrenia
  6. 4 classes of antipsychotics
    • phenothiazines
    • thioxanthenes
    • butyrophenones
    • atypical antipsychotics
  7. Characteristics of Phenothiazines
    • Tricyclic structure
    • alliphatic
    • piperidine
    • piperazine
  8. Aliphatic phenothiazines
    • chlorpromazine
    • triflupromazine
  9. Piperidine phenothiazines
    • less potent
    • less extrapyrimidal and sedative effects
    • weight gain
    • thioridazine
    • mesoridazine
  10. Piperazine phenothiazines
    • potent in low doses
    • least sedative/hypotension
    • more severe extrapyrimidal effects
    • fluphenazine
    • trifluoperazine
    • perphenazine
  11. Thioxanthines
    • less potent than phenothiazine analogs
    • aliphatic thioxanthenes
    • piperazine thioxanthenes
  12. Butyrophenones
    • Haloperidol
    • more potent with fewer autonomic effects
    • more sever extrapyramidal effects
  13. Antipsychotic effects
    • suppression of conditioned responses
    • haloperidol and piperazines are most potent
  14. Increased dopamine activity in the mesolimbic and mesocortical areas is proposed to
    cause psychosis related abnormal behaviors
  15. Antipsychotic drugs tend to...
    block dopamine receptors within ranges that suppress psychotic behaviors
  16. Mesolimbic-mesocortical pathway
    • substantia nigra to limbic system and neocortex
    • behavioral control
  17. Nigrostriatal pathway
    voluntary movement coordination
  18. Tuberoinfundibular pathway
    neuroendocrine regulation
  19. Incertohypothalamic pathway
    • amygdala
    • behavioral regulation
  20. CNS side effects and toxicity of antipsychotics
    • depression and sedation
    • decreased seizure threshold
    • depression of chemoreceptor trigger zone
    • extrapyramidal symptoms
    • tardive dyskinesia
  21. Antipsychotics that are most potent depression and sedation causers
    aliphatics
  22. antipsychotics responsible for decreased seizure threshold
    aliphatics
  23. antipsychotics that depress chemoreceptor trigger zone
    thioridazine
  24. antipsychotics that result in extrapyramidal symptoms
    • piperazines
    • butyrophenones
    • due to DA receptor blockade in basal ganglia
  25. Cause of Tardive dyskinesia
    • DA receptor supersensitivity in basal ganglia
    • relative cholinergic deficiency
  26. Extrapyramidal symptoms
    • PD syndrome
    • Akathisia
    • Acute dystonia
    • catatonia, hyperthermia
    • neuroleptic malignant syndrome
  27. Treatment for PD syndrome
    muscarinic drugs or amantadine
  28. strong subjective feeling sof distress and discomfort, compulsion for constant movement
    akathisia
  29. Treatment of akathisia
    • dose reduction of antipsychotics
    • anti-pd drugs
    • sedative antihistamines with anticholinergic properties
  30. treatment for acute dystonia
    anticholinergic anti-PD drugs
  31. antipsychotics which may cause catatonia or hyperthermia
    chlopromazine or clozapine
  32. Neuronal connections in PD
    dopaminergic neurons misfunction from substantia nigra to corpus striatum
  33. 4 characteristics of tardiv dyskinesia
    • more pronounced in older patients with abrupt withdrawl of antipsychotics
    • less prominant with thioridazine (piperidine phenoxanthines) and clozapine
    • sterotyped involuntary movements
    • symptoms are untreatable and may persist indefinitely
  34. Management of tardive dyskinesia
    • discontinue or reduce dose of antipsychotic
    • switch to a newer atypical antipsychotic
    • eliminate all drugs with anticholinergic action such as anti-pd drugs and TCAs
    • use diazepam
  35. Peripheral side effects of antipsychotics
    • hyperprolactinemia and amenorrhea
    • altered body temperature regulation
    • alpha adrenergic blockade
    • anticholinergic action
    • hypersensitivity/weight gain
    • agranulocytosis
  36. Hyperprolactinemia and amenorrhea
    • inhibition of prolactin secretion by DA
    • increased conversion of androgen to estrogen
    • false positive pregnancy tests
    • infertility or impotence
    • dose reduction or use aripiprazole
  37. Alpha adrenergic blockade
    • aliphatic phenothiazines
    • orthostatic hypotension/faintness
    • palpitations
    • nasal stuffiness
  38. Anticholinergic action
    • thioridazine or tricyclic structure
    • dry mouth
    • blurred vision
    • urinary retention
    • constipation
  39. Agranulocytosis
    • 1-2% of patient taking clozapine
    • increased blood cell counts
    • weekly blood counts for first 6 weeks then every 3 weeks
  40. weight gain
    common with clozapine or olanzapine
  41. Absorption of Antipsychotics
    • unpredictable after oral administration
    • IM increases bioavailability
    • highly lipophilic and protein bound
    • long duration of action
  42. Liver metabolism of antipsychotics
    • significant first pass metabolism
    • oxidation by CYP and conjugation
    • metoabolites excreted in urin and bile
  43. Mesoridazine
    • active metabolite of thioridazine
    • more potent antipsychotic effect
  44. Drug interactions of antipsychotics with CNS depressants
    • Anticholinergic effects
    • potentiates sedatives, analgesics, alcohol, hypnotics and antihistamines
  45. Neuroleptic drugs inhibit...
    action of dopaminergic agonists and levodopa
  46. antipsychotic drugs with anti-hypertensive agents
    • blocks antihypertensive effects of guanethidine
    • alpha adrenergic blocking action
    • postural hypotension
  47. antipsychotics with digoxin
    thioridazine and ziprasidone may partially nullify the ionotropic effect of digoxin
  48. Therapeutic uses of antipsychotics
    • psychosis, mania, severe agitation schizophrenia
    • delusional paranoia
    • antinauseant
    • hiccough and pruritis
    • tourette's syndrome
    • huntington's disease
    • anesthesia
  49. used for treatment of delusional paranoid state
    fluphenazine
  50. mechanism of anti-nausiants
    block DA receptors centrally and peripherally
  51. Drugs used as anti nauseants
    • prochlorperazine
    • benzquinamide
  52. used for pruritus
    trimeprazine
  53. used for huntington's disease
    haloperidol
  54. drugs used for anesthesia
    butyrophenone droperidol with fentanyl to provide neuroleptanesthesia
  55. New antipsychotic drugs
    • clozapine
    • olanzapine
    • quetipine
    • risperidone
    • aripiprazole
  56. Clozapine
    • high seratonin potency
    • potent anti-cholinergic
    • limited D2 receptor blockade
    • fatal agranulocytosis
    • used for older patients with dementia
  57. Olanzapine
    • most tolerable atypical antipsychotic
    • not for older adult patients with dementia
  58. qutiapine
    most prescribed
  59. risperidone
    • similar to clozapine
    • more potent DA antagonism
    • less side effects (anticholinergic and sedative effects)
  60. aripiprazole
    • low weight gain
    • long half life

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