Antipsychotics Overview

Types of Antipsychotics

• First Generation (Typical) Antipsychotics
  • Work by strongly blocking dopamine (D2) receptors
  • Cause more motor and neurologic side effects
• Second Generation (Atypical) Antipsychotics
  • Less affinity for dopamine receptors
  • Cause metabolic issues (e.g., obesity, diabetes, hyperlipidemia)

Important Concepts

• Dopamine Receptor (D2)

  • First generation antipsychotics work on D2 receptor
  • Mnemonic: D2R sounds like dour, indicating withdrawal from reality

• Effects of Dopamine

  • Mnemonic: DOPAMINE
    • D: Drive
    • O: Psychosis
    • P: Parkinsonism
    • A: Attention
    • M: Motor
    • I: Inhibition of prolactin
    • N: Narcotics
    • E: Extrapyramidal

Antipsychotic Side Effects

Motor and Cognitive Effects

• Induce Parkinson's-like symptoms
  • Antipsychotics can cause motor and cognitive effects similar to Parkinson's disease

Extrapyramidal Side Effects

• Types and Timing
  • Acute Dystonia: Muscle contractions, onset in hours
  • Akathisia: Restlessness, onset in days
  • Akinesia: Decreased movement, onset in weeks
• Mnemonic: Muscle, Russell, and Hustle
  • Muscle: Acute dystonia
  • Russell: Akathisia (restlessness)
  • Hustle: Akinesia (reduced movement)

Tardive Dyskinesia

• Involuntary rhythmic movements
• Irreversible side effect of long-term use
• 3-5% risk per year on first-generation antipsychotics

Hyperprolactinemia

• Caused by inhibition of dopamine
• Linked to breast enlargement
• Notable with Risperidone

Neuroleptic Malignant Syndrome (NMS)

• Serious condition with 15% mortality
• Symptoms: Confusion, hyperthermia, muscle rigidity
• Treatment: Dantrolene or dopamine agonists

Dosing Forms

• Oral: Common but reliant on patient compliance
• Dissolvable: Prevents 'cheeking,' used in hospitals
• Intravenous (IV): Gold standard, used for acute management
• Intramuscular (IM): Useful for agitated patients; long-acting depot forms available
• Mnemonic: PO before DEPO to prevent allergic reactions

Specific Antipsychotics

First Generation

• Chlorpromazine: Targets multiple receptors, causes corneal deposits
• Thioridazine: Causes retinal deposits
• Haloperidol (Haldol): High D2 selectivity, high EPS risk

Second Generation

• Clozapine: Effective but risk of agranulocytosis
  • Requires regular ANC monitoring
• Olanzapine (Zyprexa): Effective but high metabolic side effects
• Risperidone (Risperdal): Less sedating, risk of gynecomastia
• Quetiapine (Seroquel): Sedating, used for quieting
• Ziprasidone (Geodon): Prolongs QT interval
• Aripiprazole (Abilify): Partial agonist, used for maintenance and depression augmentation

Clinical Considerations

• Antipsychotics should be managed by a physician trained in mental health
• Be aware of metabolic and neurologic side effects for potential treatment