A 28-year-old man on haloperidol 10 mg daily for schizophrenia develops fever (39.5°C), severe muscle rigidity, altered consciousness, and elevated creatine kinase (2800 U/L) over 4 days. Regarding neuroleptic malignant syndrome (NMS), all of the following are true EXCEPT:

Explanation

## Neuroleptic Malignant Syndrome (NMS): Management & Pathophysiology **Key Point:** NMS is a rare but life-threatening idiosyncratic reaction to antipsychotics characterized by the tetrad of fever, rigidity, altered mental status, and autonomic instability. Management requires immediate drug cessation and supportive care; dopamine agonists are FIRST-LINE, not contraindicated. ### Management of NMS: First-Line Interventions **High-Yield:** The cornerstone of NMS management is: 1. **Immediate discontinuation** of the offending antipsychotic (most critical step) 2. **Supportive care**: IV fluids, cooling measures, monitoring of renal function 3. **Pharmacological intervention**: Dopamine agonists (bromocriptine) or dantrolene ### Dopamine Agonists in NMS **Clinical Pearl:** Bromocriptine and other dopamine agonists are **INDICATED and RECOMMENDED** in NMS, not contraindicated. They restore dopaminergic tone in the basal ganglia, which is depleted by antipsychotics. | Agent | Mechanism | Dosing | Role in NMS | |---|---|---|---| | **Bromocriptine** | D~2~ agonist | 2.5–15 mg/day in divided doses | **First-line pharmacotherapy** | | **Amantadine** | NMDA antagonist + dopamine releaser | 100–300 mg/day | Alternative agent | | **Dantrolene** | Skeletal muscle relaxant (Ca²⁺ release blocker) | 1–10 mg/kg/day | Adjunctive for severe rigidity | **Mnemonic — NMS MANAGEMENT: DRAB** - **D**iscontinue antipsychotic immediately - **R**ehydrate aggressively (IV fluids) - **A**gents: bromocriptine or dantrolene - **B**rain cooling (external/internal measures) ### Dantrolene: Mechanism & Role **Key Point:** Dantrolene sodium is a skeletal muscle relaxant that blocks calcium release from the sarcoplasmic reticulum via the ryanodine receptor. This reduces muscle contraction and is particularly useful in severe NMS with life-threatening rigidity. The statement about dantrolene's mechanism is **TRUE**. ### Creatine Kinase Elevation in NMS **High-Yield:** Severe muscle rigidity causes: - Rhabdomyolysis (muscle breakdown) - Myoglobinuria (myoglobin in urine) - Acute kidney injury (AKI) risk - CK elevation (often > 1000 U/L, sometimes > 10,000 U/L) The elevated CK in this case (2800 U/L) reflects active rhabdomyolysis and is a marker of severity. This statement is **TRUE**. ### Pathophysiology of NMS ```mermaid flowchart TD A[Antipsychotic administration]:::action --> B[Dopamine D2 blockade<br/>in basal ganglia]:::outcome B --> C[Loss of dopaminergic tone]:::outcome C --> D[Increased muscle rigidity<br/>and heat production]:::outcome D --> E[Hyperthermia]:::outcome D --> F[Rhabdomyolysis]:::outcome F --> G[Myoglobinuria &<br/>Acute Kidney Injury]:::urgent E --> H{Management?}:::decision H -->|First step| I[Stop antipsychotic]:::action H -->|Pharmacotherapy| J[Bromocriptine or Dantrolene]:::action I --> K[Recovery]:::outcome ``` **Tip:** On NEET PG, remember that dopamine agonists are **therapeutic** in NMS, not harmful. This is a common misconception among students who confuse NMS with other conditions. [cite:Harrison 21e Ch 396; Kaplan & Sadock 20e Ch 29]