Dantrolene: Mechanism of Action and Adverse Side Effects
Medication indicated for the treatment of muscle spasms associated with malignant hyperthermia (reaction to certain anesthetics resulting in a rapid and dangerous increase in body temperature, muscle rigidity, and other symptoms), and spasticity associated with various neurological disorders such as multiple sclerosis, cerebral palsy, and spinal cord injury.
Dantrolene
Authors: Madison Amyotte, Arzina Jaffer Reviewers: Jasleen Brar, Mao Ding Luiza Radu Joanna Moser* * MD at time of publication
Metabolized in the liver by the cytochrome P450 enzyme
Metabolic process forms a high concentration of hydroxylamine
Hydroxylamine is a highly toxic metabolite associated with dantrolene induced liver injury
Impaired Liver Function
Binds to ryanodine receptors (RYR1) in the sarcoplasmic reticulum of skeletal muscle cells
Prevents ryanodine channel from opening when triggered by the action potential in the muscle
Prevents calcium release from the sarcoplasmic reticulum
Prevents binding of calcium to troponin on the actin filaments in the cytosol of the skeletal muscle cells
Myosin-binding site on the actin remains covered by the tropomyosin
Prevents cross-bridge formation between myosin and actin within the sarcomere
Prevents muscle contraction
↓ Progression of muscle rigidity and spasms ↓ Heat produced by muscular contraction
Skeletal & respiratory muscle weakness ↓ Body temperature
↓ Inspiratory capacity
Dyspnea
Legend:
Pathophysiology
Mechanism
Sign/Symptom/Lab Finding
Complications
Published Feb 18, 2024 on www.thecalgaryguide.com