Which condition is described as a pharmacogenetic disorder triggered by certain anesthetics causing uncontrolled calcium release and hypermetabolism?

Which condition is described as a pharmacogenetic disorder triggered by certain anesthetics causing uncontrolled calcium release and hypermetabolism?

• A. Malignant hyperthermia.
• B. Fever.
• C. Heat stroke.
• D. Rhabdomyolysis.

Answer: (A)

This describes malignant hyperthermia, a genetic susceptibility in how skeletal muscle handles calcium. In people with this pharmacogenetic predisposition, certain anesthetic agents—especially volatile inhaled anesthetics and the depolarizing muscle relaxant succinylcholine—trigger an uncontrolled release of calcium from the motor‑protein storage site in muscle (the sarcoplasmic reticulum, via the ryanodine receptor). That sudden calcium surge drives continuous, forceful muscle contraction and a surge in metabolic activity, so the muscle consumes ATP at a huge rate, generating a lot of heat and carbon dioxide. The result is a rapid, dangerous hypermetabolic state with tachycardia, rising CO2 and body temperature, metabolic acidosis, and potential muscle breakdown (rhabdomyolysis) if not treated promptly. Because the abnormal calcium handling is genetic and the reaction is provoked specifically by certain anesthetics, it’s classified as a pharmacogenetic disorder. Treatment revolves around stopping the triggering agents and administering dantrolene, which inhibits the calcium release channel, along with aggressive cooling and supportive care.

This describes malignant hyperthermia, a genetic susceptibility in how skeletal muscle handles calcium. In people with this pharmacogenetic predisposition, certain anesthetic agents—especially volatile inhaled anesthetics and the depolarizing muscle relaxant succinylcholine—trigger an uncontrolled release of calcium from the motor‑protein storage site in muscle (the sarcoplasmic reticulum, via the ryanodine receptor). That sudden calcium surge drives continuous, forceful muscle contraction and a surge in metabolic activity, so the muscle consumes ATP at a huge rate, generating a lot of heat and carbon dioxide. The result is a rapid, dangerous hypermetabolic state with tachycardia, rising CO2 and body temperature, metabolic acidosis, and potential muscle breakdown (rhabdomyolysis) if not treated promptly. Because the abnormal calcium handling is genetic and the reaction is provoked specifically by certain anesthetics, it’s classified as a pharmacogenetic disorder. Treatment revolves around stopping the triggering agents and administering dantrolene, which inhibits the calcium release channel, along with aggressive cooling and supportive care.