Dantrolene

Summary

Dantrolene is a muscle relaxant used to treat malignant hyperthermia and neuroleptic malignant syndrome.  Dantrolene works by blocking Ryanodine receptors on the sarcoplasmic reticulum of skeletal muscles, which reduces calcium release into the cell. Reduction of calcium levels in turn prevents muscle contraction. Dantrolene is used to treat malignant hyperthermia, a condition of sustained muscle contraction in response to administering drugs like inhaled anesthetics or succinylcholine. Dantrolene is also used to treat neuroleptic malignant syndrome, another adverse reaction involving muscle contractions and rigidity after taking antipsychotic drugs.

Key Points

• Dantrolene
  • Mechanism
    • Blocks ryanodine receptors
      • Prevents release of Ca2+ from sarcoplasmic reticulum of skeletal muscle by inhibiting the ryanodine receptor
      • Decreases excitation-contraction coupling
      • Decreases Ca2+ release from the sarcoplasmic reticulum in skeletal muscle
  • Clinical Use        
    • Treats Malignant hyperthermia
      • Hypermetabolic crisis secondary to inhaled anesthetic use (e.g., halothane) or succinylcholine
        • Patients have a genetic abnormality in ryanodine or dihydropyridine receptors, a skeletal muscle protein
          • results in excessive Ca2+ release from the sarcoplasmic reticulum
          • Hyperthermia, muscle rigidity, and AMS
      • Malignant hyperthermia can result from toxicity of inhaled anesthetics and succinylcholine
    • Treats Neuroleptic malignant syndrome (NMS)
      • Medical emergency secondary to drugs with dopamine antagonist properties (e.g. antipsychotics, metoclopramide) characterized by:
        • motor impairment, muscle rigidity, akinesia, or extrapyramidal signs
        • hyperthermia        
        • mental status change
        • autonomic dysfunction
      • To distinguish vs. serotonin syndrome: Typical features in these patients (SS) that are not often seen in NMS patients are shivering, hyperreflexia, myoclonus, and ataxia