Malignant dantrolene

The answer is e. (Kat ung, pp 428-429J Although a rare occurrence, halothane and other inhaled gas anesthetics may cause malignant hyperthermia Apparently, this occurs in genetically susceptible individuals Its onset may be accelerated by the concomitant use of succinylcholine. Immediate treatment includes administration of dantrolene. 

Dantrolene interferes with electromechanical coupling in the muscle cell by inhibiting Ca + release from the SR. It is used to treat painful muscle spasms attending spinal diseases and skeletal muscle disorders involving excessive release of Ca + (malignant hyperthermia). 

Chronic use of neuroleptics can, on occasion, give rise to hepatic damage associated with cholestasis. A very rare, but dramatic, adverse effect is the malignant neuroleptic syndrome (skeletal muscle rigidity, hyperthermia, stupor) that can end fatally in the absence of intensive countermeasures (including treatment with dantrolene, p. 182). 

Skeletal muscle relaxants may be nsed for relief of spasticity in nenromnscular diseases, snch as multiple sclerosis, as well as for spinal cord injnry and stroke. They may also be used for pain relief in minor strain injnries and control of the mnscle symptoms of tetanus. Dantrolene (Dantrium) has been nsed to prevent or treat malignant hyperthermia in surgery. 

Succinylcholine-induced hyperkalemia may lead to cardiac arrhythmia and arrest when plasma reaches 7 and 10 mM, respectively. The drug also may precipitate a fulminant attack of malignant hyperthermia in susceptible individuals (not to be confused with neuroleptic malignant hyperpyrexia, which involves dopamine and the CNS). Treatment in either case consists of cooling the body and administering oxygen and dantrolene sodium (discussed later). 

Dantrolene is active orally, although its absorption is slow and incomplete. Its biological half-life (h/z) is 8.7 hours in adults. The drug is metabolized by liver microsomal enzymes and is eliminated in the urine and bUe. It is given IV when treating an attack of malignant hyperthermia. 

A rare, but potentially fatal idiosyncratic adverse effect is neuroleptic malignant syndrome. This can occur with any antipsychotic drug. The symptoms are rigidity, hyperthermia, autonomic lability, and reduced level of consciousness. Massively elevated levels of creatinine kinase are usually found. Prior to 1984, the mortality rate was around 25% but improved early recognition has considerably reduced this. Management is cessation of antipsychotics, appropriate conservative measures and dantrolene if necessary for muscle rigidity. 

Malignant hyperthermia Volatile anesthetics, succinylcholine Hyperthermia, muscle rigidity, hypertension, tachycardia onset within minutes Dantrolene, cooling... 

A rare interaction of succinylcholine with volatile anesthetics results in malignant hyperthermia, a condition caused by abnormal release of calcium from stores in skeletal muscle. This condition is treated with dantrolene and is discussed below under Spasmolytic Drugs and in Chapter 16. 

Lopez JR et al Effects of dantrolene on myoplasmic free [Ca2+] measured in vivo in patients susceptible to malignant hyperthermia. Anesthesiology 1992 76 711. [PMID 1575338]... 

Note Many drugs and toxins block neuromuscular transmission by other mechanisms, such as interference with the synthesis or release of acetylcholine, but most of these agents are not employed clinically for this purpose. One exception is botulinus toxin, which has been administered locally into muscles of the orbit in the management of blepharospasm and strabismus. This treatment produces a long-lasting interruption of neuromuscular transmission and reduction of spasmodic ocular movements. Another exception is dantrolene, which blocks release of Ca2+ from the sarcoplasmic reticulum and is used in the treatment of malignant hyperthermia. 

Dantrolene, a hydantoin derivative, reduces the contraction of skeletal muscle, acting directly on the muscle and not at the neuromuscular junction. It is thought to reduce the amount of calcium released and hence prevent excitation-contraction coupling (Figure 26.4). Its usefulness in the treatment of anesthetic-induced malignant hyperthermia may be due to its calcium-related uncoupling actions. 

A special application of dantrolene is in the treatment of malignant hyperthermia, a rare heritable... 

Coons, D. J., Hillman, F. J., Marshall, R. W. (1982). Treatment of neuroleptic malignant syndrome with dantrolene sodium A case report. American Journal of Psychiatry, 139, 943-945. 

Dantrolene may be effective in reducing muscle rigidity in neuroleptic malignant syndrome (388,389) (SEDA-20, 42), but a reliable regimen has not been established (390). 

Goekoop JG, Carbaat PA. Treatment of neuroleptic malignant syndrome with dantrolene. Lancet 1982 2(8288) 49-50. 

---