Psychotherapy: 99b - Antipsychotics

Blockade of the mesolimbic D2 dopamine receptors

• High-potency agents (Haloperidol, Trifluoperazine, Fluphenazine) bind more tightly to D2 dopamine receptors
  

  • More extrapyramidal side effects

• Low potency agents (Thioridazine, Chlorpromazine) bind less tightly to D2 dopamine receptors
  

  • Fewer extrapyramidal side effects

  • More side effects due to anticholinergic, antihistamine effect

• Ziprazidone

• Aripiprazile

• Lurasidone

Clozapine (Atypical/2nd generation)

May cause potentially fatal neutropenia and agranulocytosis

As a result, used as a 3rd line agent despite efficacy; patients must register in database to document neutropenic reaction/prevent prescription in the future

• Efficacy = ability to achieve the desired clinical effect

• Potency = how much medication is needed
  

  • Higher potency = lower systemic levels needed for effect

• 1st generation (FGA)
  

  • Only treat positive symptoms of schizophrenia

• 2nd generation (SGA)
  

  • Treat positive and negative symptoms of schizophrenia

  • More likely to have metabolic side effects

Both low-potency FGAs and all SGAs may causesedation, orthostatic hypotension, antimuscarinic, neuroleptic malignant sydrome

• Lead pipe rigidity

• Autonomic: sweating, tachycardia

• Mental status change

• Rhabdomyolysis

Most likely in high-potency FGAs (haloperidol, trifluoperazine, fluphenazine)

Nigrostriatal tract

Involved in fine control of movement

• Acute dystonia

• Parkinsonism

• Tardive Dyskinesia with long-term use

• Quetiapine

• Ziprasidone

• Olanzapine

• Risperidone (whisperidone)

• Aripiprazole

• Lurasidone

• Clozapine

Quiet! Zip it! Onlyw(r)hispers area(r)propriate in thisLittleclozet!

Low potency FGAs = Thioridazine, Chlorpromazine

• Sedation
  

  • Due to histamine blockade (may be useful in the hospital)

• Dry mouth, urinary retention, constipation, blurred vision
  

  • Due to muscarinic blockade

• Orthostatic hypotension
  

  • Due to alpha-1 blockade

• Neuroleptic malignant syndrome
  

  • But less likely than 1st generation

Note: extrapyramidal, hypergallactorea, tardive dyskinesia much less likely

Mesolimbic dopamine system

Involved in emotions, motivation, and goal-oriented behavior

• Blocking the nigrostriatal tract results in the extrapyramidal side effects of antipsychotic medications
  

  • Acute dystonia

  • Parkinsonism

  • Tardive Dyskinesia with long-term use

• Haloperidol*

• Trifluoperazine*

• Fluphenazine*

• Thioridazine

• Chlorpromazine

* = high potency

Hal tried to fly but Thor Clorbbered him

Thor and Hal are old (like Van Gogh in the sketchy), so these are 1st gen

(The r in thor matches chlorpromazine; don’t get confused with clozapine, a 2nd gen)

High potency FGA = haloperidol, trifluoperazine, fluphenazine

• Extrapyramidal symptoms
  

  • Parkinsonism

  • Dystonia

  • Tardive dskenesia after years of use

• Hyperprolactinemia

• Higher risk of neuroleptic malignant syndrome

Schizophenia is the most common use

Other uses include

• 1st generation
  

  • Acute psychotic episodes in many conditions

  • Acute agitation and aggression (especially haloperidol)

• 2nd generation
  

  • Treatment-resistant depression

  • OCD ad-junct (with SSRIs)

Extrapyramidal effects are movement-related side effects of dopamine blockade

Most likely caused by high-potency FGAs (Haloperidol, Trifluoperazine, Fluphenazine)

• Dystonic reactions (acute, painful, involuntary muscle spasm)

• Drug-induced parkinsonism

• Akathisia (restlessness, anxiety)

• Tardive Dyskinesia
  

  • Occurs after long term use

Block D2 receptors in the CNS

Block 5-HT 2A receptors

-> Treat + and - symptoms of schizophrenia with fewer movement-related side effects