Pharm for Psychotic disorders

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jncates
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211050
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Pharm for Psychotic disorders
Updated:
2013-04-02 20:57:06
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Pharmacology Psychotic
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pharmacology for the treatment of psychosis
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  1. Schizophrenia
    disturbances lasts for atleast 6 months including atleast 1 mont of 2 or more of the following:

    • Delusions
    • Hallucinations
    • Disorganized speech
    • Grossly disorganized or catatonic behavior
    • Negative symptoms
  2. Schizophreniform Disorder
    schizophrenia but less than 6 months duration
  3. Brief Psychotic Disorder
    schizoprhenia lasting only 1 day to 1 month
  4. Schizo-Affective Disorder
    Mood disturbances and schizophrenia
  5. Schizophrenia Positive Symptoms
    • Hallucinations
    • Delusions
    • Disorganized thought
    • Behavioral disturbances
    • Combativeness
    • Disorganized speech
    • Tension
  6. Schizophrenia Negative Symptoms
    • Blunted emotions
    • Psychomotor retardation
    • Avolition - no drive
    • Alogia - poverty of speech
    • Anhedonia - no pleasure
    • Social withdrawal
    • Loss of executive functions
  7. Types of Delusions
    Persecution: paranoia (they are out to get me)

    Grandeur: megalomania (God Complex)

    Being Controlled: (the CIA is controlling my brain with a radio signal
  8. The Course of Schizophrenia
    Prodromal Phase:  gradual development of symptoms... (negative predominate)

    • Active Phase:  onset of positive symptoms
    • Acute Phase - impairment often severe... positive symptoms predominate and are responsive to treatment
    • Stable Phase - negative symptoms predominate... impairment can be moderate
  9. Dopamine Hypothesis for Schizophrenia
    increased dopaminergic activity in the MESOLIMBIC pathway

    all antipsychotics block D2 receptors

    amphetamines and cocaine can cause psychosis that resembles positive symptoms

    Most antipsychotics can produce acute EPS's reflecting a decrease in central dopaminergic activity... with continued use tardive dyskinesia can occur
  10. Typical Antipsychotic Drugs
    • Phenothiazines (potency low to high)
    • Chloropromazine (aliphatic)
    • Thioridazine (Piperidine)
    • Fluphenazine (Piperazine)
    • *All have equal Efficacy

    Butyrophenones (Haloperidol)
  11. Atypical Antipsychotic Drugs
    • Clozapine
    • Risperidone
    • Olanzapine

    DA System Stabilizers (aripiprazole)
  12. R2 group in phenothiazines
    all antipsychotics have an R2 group containing a 3 carbon spacer

    Phenothiazines with a 2 carbon spacer have clinically effective antiemetic/antihistaminic activity but no antipsychotic (promethazine)
  13. Actions of D2 receptors in different pathways in the CNS and typical antipsychotic
    Mesolimbic - arousal, memory, behavior - treats positive and negative symptoms

    Nigrostriatal - motor activity - EPS

    Tubero-infundibular - inhibits prolactin release - increased prolactin release
  14. Phenothiazines Receptor Binding
    • D2 - dopamine
    • M1-3 Muscarinic
    • H1 - Histamine
    • a1 - adrenergic

    side effects of typical antipsychotics depend on their potency at D2 receptors...

    Higher potency drugs (piperazines) have fewer side effects due to blockade of the other receptors
  15. CNS Effects of Phenothiazines
    • Sedation - H1 receptor blockade 
    • low potency more problematic

    • Lowered Seizure threshold
    • low potency more problematic

    • EPS - blocking nigrostriatal pathway
    • ♦ occur early in treatment
    • ♦ eventually disappear but must be treated
    • ♦ higher potency more problematic
    • ♦ Thioridazine has the lowest incidence since its also a strong antimuscarinic
  16. Acute EPS with Phenothiazines
    Dystonia - onset 1-5 days... more common in young

    • Muscle Spasms
    • spasm of the neck (torticollis)
    • upward deviation of the eyes (oculogyric crisis)
    • spasms of the jaw and tongue (oromandibular dystonia)
    • Parkinsonism - onset 2 wks to 2 months

    • Akathisia - onset 1-3 months
    • extreme motor restlessness
    • should be discerned from agitation
    • most common acute EPS

    • Neuroleptic Malignant Syndrome
    • medical emergency - potentially fatal
    • hyperthermia, muscle rigidity, autonomic instabilitiy

  17. Chronic EPS with Phenothiazines
    • Tardive Dyskinesia
    • repetitive, involuntary, movements of the facial musculature, arms and trunk

    not predictable from chemistry

    DISUSE supersensitivity

    • Treatment: NONE
    • discontinue antimuscarinic
    • switch to clozapine or other atypical
    • BDZ, Propranolol, Lecithin/ Choline
  18. Endocrine Effects of Phenothiazines
    Hyperprolactinema b/c of inhibition of the tubero-infundibular pathway... stops the dopamine projection from the arcuate nucleus

    all potency's equally problematic here

    • In Women
    • amenorrhea, Galactorrhea, False positive pregnancy tests

    • In Men
    • gynecomastia
  19. Autonomic Effects of Phenothiazines
    • a1 blockade (low potency more problematic)
    • Nasal Stuffiness
    • Orthostatic Hypotension
    • Ejaculatory Disturbances

    • Muscarinic Blockade (Dine > aliphatic > zine)
    • dry mouth
    • blurred vision
    • constipation
    • urinary retention
    • mydriasis
    • decreased sweating
    • male impotence
  20. Cardiovascular Effects of Phenothiazines
    • ECG changes
    • QTc interval - time for ventricular depolarization and repolarization

    Thioridazine blocks potassium channels to prolong QTc interval
  21. Metabolic and Hepatic Effects of Phenothiazines
    • Temperature Dysregulation
    • Hyperpyrexia - avoid heat and sun (heat stroke)
    • Hypopyrexia

    Obstructive jaundice (low potency more problematic)
  22. Dermatologic and Ophthalmologic Effects of Phenothiazines
    • Skin
    • Photosensitivity
    • Hyperpigmentation

    • Eyes
    • Pigmentary Retinopathy (potential blindness)
    • discontinue APD
  23. Drug interactions with Phenothiazines
    • L-Dopa and Bromocriptine
    • antagonized by phenothiazines

    • CNS depressants
    • additive effect with other depressants
    • opiods
    • ethanol
    • antihistamines
  24. Butyrophenones
    Haloperidol - most commonly used

    • Droperidol
    • Antiemetic
    • Neurolept Analgesia (+ fentanyl)
    • Neurolept Anesthesia (+ fentanyl and N2O)

    Side Effects - Like a high potency Phenothiazine (Piperazine)
  25. Atypical Antipsychotics benefits and Side effects
    Greater efficacy for negative symptoms

    Lower incidence of Acute EPS's

    Lower incidence of Tardive Dyskinesia

    Can produce Hyperglycemia and Type 2 Diabetes
  26. Atypical Antipsychotics mechanism and hypothesis
    atypicals block D2 receptors and 5-HT2A receptors

    Serotonin inhibits DA activity in certain pathways

    Negative symptoms are caused by decreased DA activity in mesocortical pathway
  27. Atypical Antipsychotic receptor blocks in parts of the brain
    mesolimbic - decrease positive and negative symptoms by decreasing DA

    mesocortical - decrease negative symptoms by increasing DA

    Nigrostriatal - few EPS's

    Tubero-infundibular - little effect on prolactin release
  28. Clozapine Side Effects
    • similar to low potency PTZ...
    • Especially sedation, seizures, ortho hypo
    • Lack of EPS's
    • Little prolactin elevation

    • Agranulocytosis - potentially fatal
    • baseline WBC followed by weekly WBC

    • Sialorrhea - excessive drooling
    • factor in noncompliance

    Weight Gain - average 10 lbs at 10 weeks
  29. Clozapine Uses
    Treatment-resistant Schizophrenics

    • Treatment-intolerant Schizophrenics
    •       Tardive Dyskinesia
    •       Psychotic disorder with Parkinson's

    Parkinson's Disease - Iatrogenic Psychosis
  30. Other Atypical Antipsychotics Side Effects
    • Risperidone
    • weight gain

    • Olanzapine
    • weight gain, type 2 diabetes

    • Quetiapine
    • weight gain, cataracts

    • Ziprasidone
    • QTc prolongation, no weight gain

    All have similar side effects to high potency PTZ's except few acute EPS's and lower than typicals in Tardive
  31. Aripiprazole (Abilify)
    Dopamine system stabilizer

    no weight gain, no QTc prolongation

    partial agonist at D2 receptors and antagonist at 5HT2A receptors
  32. Therapeutic Indications for psychiatric disorders
    • Bipolar I disorder
    • Mania (Acute Phase)
    • haloperidol until lithium takes effect
    • atypical antipsychotics (not Clozapine)
    • aripiprazole

    • Maintenance Phase
    • Olanzapine, Quetiapine, Ziprasidone, Aripiprazole

    • Major Depressive Disorder
    • Adjunctive treatment of depression
    • Aripiprazole, Olanzapine
  33. Neurological Therapeutic Indications for antipsychotic use
    • Hyperkinetic Extrapyramidal Disorders
    • Huntington's Disease
    • loss of cholinergic neurons in striatum... Haloperidol

    • Tourette's Disorder
    • Haloperidol / Pimozide
    • treats tics but not Coprolalia
  34. Substance Abuse Reactions for uses of antipsychotic treatment
    • acute intoxication with CNS stimulants
    • Cocaine, Amphetamine
    • haloperidol for acute psychosis

    • Post Hallucinogen Perception Disorder
    • PCP / Hallucinogens (LSD)
    • Treat with Haloperidol if frequent
  35. Anti-Emetic Uses for antipsychotics
    • Phenothiazines
    • Prochlorperazine
    • Perphenazine
    • NOT thioridazine

    • Butyrophenones
    • Droperidol
  36. Treatment of Dystonia and Parkinsonism in Acute EPS
    • Benztropine
    • Diphenhydramine
    • Amantadine
    • Lower dose
  37. Treatment of Akathisia in Acute EPS
    • Propranolol 
    • Lorazepam
    • Benztropine or Diphenhydramine
    • lower dose or different one
  38. Treatment of Neuroleptic Malignant Syndrome in Acute EPS
    • Dantrolene
    • Bromocriptine
    • Diazepam
    • discontinue antipsychotic agent

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