Mnemonic

Antipsychotics are thought to work by blocking the D2 receptor. Psychotic patients sometimes take a DetouR from reality.

• First-generation antipsychotics (also called typical antipsychotics): block D2 receptor → ↑ cAMP
  • High-potency antipsychotics have a strong antipsychotic effect even at relatively low doses, but they also more commonly cause neurologic side effects (e.g., extrapyramidal symptoms) than low-potency antipsychotics.
    • Haloperidol
    • Fluphenazine
    • Perphenazine
    • Trifluoperazine
    • Pimozide
  • Low-potency antipsychotics more commonly cause anticholinergic, antihistamine, and sympathetic α1-blockade effects.
    • Chlorpromazine
    • Thioridazine
  • Stored in fat tissue (lipid soluble) and, therefore, only slowly eliminated from the body.
• Second-generation antipsychotics (also called atypical antipsychotics): most are 5-HT2 and D2 antagonists with varying α and H1 receptor effects
  • Serotonin antagonism can help modulate dopamine, reducing its EPS side effect.
  • Also can improved negative and cognitive symptoms

First-generation antipsychotics (FGAs)

High-potency

Haloperidol

• Brand name: Haldol
• High-potency antipsychotics
  • Dopamine-specific antagonism (D2 receptor)
• Extrapyramidal symptoms most common in high-potency FGAs
  • HOLD-ol

Adverse effects

• Hyperprolactinemia
  • Dopamine inhibits the release of prolactin via the D2 receptor in the tuberoinfundibular pathway. Therefore, dopamine antagonists increase the effects of prolactin.
• Extrapyramidal symptoms most common in high-potency FGAs
• Prolonged QT interval
• Neuroleptic malignant syndrome

Low-potency

Chlorpromazine

• Low-potency antipsychotics
  • Dopamine antagonism
  • Anticholinergic
  • Antihistaminergic
• First discovered, wide range of indications
• Corneal deposits

Mnemonic

氯丙嗪，治精神；阻断多巴Ma不灵。止吐冬眠和降温，就是不治晕动病。不良反应帕金森，张口伸舌坐不能。口干好似阿托品，乳汁分泌羞死人。

Mnemonic

Chlor-neal deposits

Adverse effects

• Anticholinergic effects, sympatholytic effects, metabolic effects, and sedation dominate
  • Sedation due to histamine receptor blockade, see Antihistamines

Difference of Adverse Effects

Low-potency antipsychotics require higher doses to achieve the desired effect, which leads to more prominent blockage of other receptors except D2.

Second-generation antipsychotics (SGAs)

Clozapine

• Most effective antipsychotic
• Indications
  • Treatment-resistant schizophrenia
  • Schizophrenia associated with suicidality
• Clozapine can cause agranulocytosis and lowers the seizure threshold

Mnemonic

You must watch clozapine clozely to monitor for agranulocytosis!

Olanzapine

• Second effective antipsychotic, without risk of agranulocytosis
• Metabolic effects (usually weight gain, hyperglycemia, new-onset diabetes mellitus, dyslipidemia) most prominent

Mnemonic

Olanzapine can make patients gain weight, so it’s the pharmacological choice for Anorexia nervosa

Risperidone

• Less sedation, good for elderly patients

Mnemonic

Rise and shine

Quetiapine

• More sedation

Mnemonic

Quietiapine

Adverse effects

Summary

• Extrapyramidal side effects:
  • Acute dystonic reaction: sudden-onset, sustained muscle contractions
  • Akathisia: subjective restlessness with inability to sit still
  • Drug-induced parkinsonism: tremor, rigidity, bradykinesia, masked facies
• Tardive dyskinesia:
  • Involuntary movements after chronic use (e.g., lip smacking, choreoathetoid movements)
• Neuroleptic malignant syndrome:
  • Fever, rigidity, mental status changes, autonomic instability

• First-generation antipsychotics (FGAs)
  • High-potency (eg, haloperidol)
    • Extrapyramidal symptoms (acute dystonia, akathisia, parkinsonism), tardive dyskinesia
  • Low-potency (eg, chlorpromazine)
    • Sedation, cholinergic blockade, orthostatic hypotension, weight gain
• Second-generation antipsychotics (SGAs)
  • Metabolic syndrome, weight gain
  • Extrapyramidal symptoms (less common than FGAs)

Hyperprolactinemia

• Most common in risperidone, amisulpride

Mnemonic

RISE-PAIR-idone gives RISE to a PAIR

Extrapyramidal symptoms (EPS)

• Pathophysiology: Inhibition of the nigrostriatal dopaminergic pathways results in EPS.
  • First-generation high-potency antipsychotics: D2 antagonism → EPS
  • Second-generation antipsychotics: weaker D2 antagonism → fewer EPS
• Clinical features similar to Parkinson disease: Muscle, rustle, and hustle
  • Acute dystonia
    • Onset: Hours to days
    • Painful and lasting muscle spasms and stiffness predominantly affecting the head, neck, and tongue
    • Facial grimacing, torticollis
    • Tongue protrusion or twisting
    • Oculogyric crisis (upward deviation of the eyes)
    • In severe cases: laryngospasm, opisthotonus of the back
  • Pseudoparkinsonism
    • Onset: ∼ 1–4 weeks
  • Akathisia
    • 1–8 weeks
    • Restlessness/compelling urge to move
    • Inability to sit or stand still
    • See Restless legs syndrome
  • Tardive dyskinesia
    • Months to years
    • Repetitive chewing and lip smacking
    • Choreic movements
    • Can be irreversible if drug is not discontinued

Mnemonic

Chewing Tardive

Neuroleptic malignant syndrome

Epidemiology

---

Etiology

---

• High-potency first-generation antipsychotics (most common association)
• Second-generation antipsychotics
• Other dopamine antagonists, e.g., metoclopramide, promethazine

Pathophysiology

---

• Central D2 receptor blockade in the nigrostriatal pathway and hypothalamus, resulting in movement disorders and impaired thermoregulation

Clinical features

---

• Mental status changes (encephalopathy)
  • Delirium (e.g., reduced vigilance)
  • Confusion
  • Stupor
  • Catatonia
• Parkinsonism
  • Muscle rigidity (lead-pipe rigidity)
  • Akinesia
  • Tremor
• Hyperthermia: High-grade fever is common.
• Autonomic instability
  • Tachycardia, dysrhythmias, labile blood pressure
  • Tachypnea
  • Diaphoresis

Diagnostics

---

Clinical features similar to Serotonin syndrome

Treatment

---

Link to original