Pharmacology of Psychoses/Mood Disorders Flashcards Preview

Nervous System: Unit IV > Pharmacology of Psychoses/Mood Disorders > Flashcards

Flashcards in Pharmacology of Psychoses/Mood Disorders Deck (18)
Loading flashcards...
1

Dopamine theory of schizophrenia related to MOA of antipsychotics

  •  overactivity of brain dopaminergic pathways, esp. @ mesolimbic pathway ==> positive sx of schizophrenia
    • mesolimbic = integration of sensory input and motor responses + affective/emotional data
  • + hypoactivity of (dopamine-activated) cells @ mesocortical pathway ==> negative sx of schizophrenia
    • mesocortical = involved in communication adn social abilities
  • MOA of antipsychotic drugs: via block of D2 receptors, effective in blocking positive sx
  •  

2

Evidence for the dopamine hypothesis

  • Virtually all antipsychotics block CNS dopamine receptors (postsynaptic D2).
  • Drugs that increase dopaminergic activity (levodopa-dopamine precursor; cocaine- reuptake blocker, amphetamine-dopamine releaser) can aggravate or produce schizophrenia.
  • Positron emission tomography (PET) scans show decreased D2 dopamine receptor densities in prefrontal lobes of schizophrenics, but increased densities in caudate nucleus (striatum).

3

Evidence counter to the dopamine hypothesis

  • Block of D2 receptors occurs immediately while antipsychotic effects take 3-6 weeks, suggesting secondary effects may be more important than direct effect of receptor block.
  • Clozapine is weak D2 blocker but still is an effective antipsychotic agent.
  • Additional evidence for the role of gluatamate and seratonin systems in psychosis as well.

4

Chlorpromazine: drug category, uses, NT/receptor

  • typical antipsychotic
  • treats + sx
  • MOA
    • primary: D2 receptor antagonist
    • secondary: some antagonist actions at muscarinic, alpha-1 adrenergic, and histamine receptors

5

Chlorpromazine: incidence of SE, factors in choosing drug

  • SE
    • medium extrapyramidal toxicity
    • high sedation (via antimuscarinic/antihistamine)
    • high ANS effects
      • dry mouth (antimuscarinic)
      • orthostatic hypotension (alpha1 block)
  • Factors in choice
    • Low clinical potency, high dose needed to achieve anti-psychotic effects

6

Haloperidol: drug class, use, NT/receptor

  • typical antipsychotic
  • treats positive sx
  • MOA:
    • very good D2 antagonist
    • minor alpha1 antagonist

7

Haloperidol: SE, tx of SE, factors in drug choice

  • SE
    • low sedation
    • high extrapyramidal sx (due to dopaminergic blockade):
      • acute dystonia
        • tx: antimuscarinic
      • akathisia
        • tx: reduce dose/change drug
      • pseudoparkinsonism
        • tx: anticholinergic
      • tardive dyskinesia
        • tx: prevention
    • some orthostatic hypotension (via alpha1 block)
  • Factors in drug choice
    • high efficacy, low dose
    • SE profile

8

Clozapine: drug class, use, NT/Receptor

  • atypical antipsychotic
  • treats negative sx & tx-resistant individuals
  • MOA
    • high 5HT2/D2 block (low D2/5HT2)
    • muscarinic antagonist
    • alpha1 antagonist

9

Clozapine: SE, factors in drug choice

  • SE
    • low sedation
    • Autonomic
      • orthostatic hypotension (alpha1 block)
    • agranulocytosis = low WBC production
    • weight gain
  • factors in drug choice
    • medium potency
    • reserved for pt.s that are refractory to other drugs

10

Risperidone: drug class, use, NT/Receptor

  • atypical antipsychotic
  • treats negative sx & tx-resistant individuals
  • MOA
    • low D2/5HT2 = good 5HT2 block

11

Risperidone: SE, factors in drug choice

  • minimal SE @ low doses
  • Factors in drug choice
    • high potency + low SE

12

Olanzapine: drug class, use, NT/Receptor

  • atypical antipsychotic
  • treats negative sx & tx-resistant individuals
  • MOA
    • low D2/5HT2 = good 5HT2 antagonist

13

Olanzapine: SE, factors in drug choice

  • SE
    • medium sedative effects
    • weight gain
  • factors in drug choice
    • high potency

14

Aripiprazole: SE, factors in drug choice

  • minimal SE
  • high potency

15

Aripiprazole: drug class, use, NT/Receptor

  • atypical antipsychotic
  • treats negative sx & tx-resistant individuals
  • MOA
    • low D2/5HT2 = good 5HT2 block

16

Characteristics of typical antipsychotics

  • high D2 / 5HT2A ratio = good D2 block ==>good efficacy against positive symptoms of schizophrenia. 
    • D2 block ==> extrapyramidal toxicity. 
  • high clinical potency (haloperidol-effective in lower doses)
    • greater D2 blocking activity
    • greater risk of extrapyramidal toxicity 
  • low clinical potency (chlorpromazine-effective in higher doses)
    • do not block D2 receptors as well
    • less extrapyramidal toxicity
    • larger doses necessary ==> side effects at other receptors (antimuscarinic [dry mouth, sedation], α1-blockade [hypotension], antihistamine [sedation]).

17

Characteristics of atypical antipsychotics

  • Characterized by a low D2 / 5HT2A ratio corresponding to poor D2 block yet good efficacy in schizophrenia (an “atypical” observation). 
  • The good 5HT2A block is thought to be associated with good efficacy against negative symptoms of schizophrenia as well as efficacy in treatment-resistant individuals.

18

Summary of pathophys of schizophrenia + pharmacotherapy on brain pathways