Dantrolene

StmcturaHy related to nitrofurantoias are Dantrolene [7261-97-4] (38), a peripherally acting muscle relaxant, and its analogues (39), which can be used as an antidote against succiaylcholine-iaduced myopathy and ia autoimmune myasthenia gravis therapy (136,137). 

Dantrolene sodium L-(-) - y-Amino-a-hydroxybutyric acid Amikacin... 

Dantrolene is an antidote for MH, which inhibits the CICR activity. Action of dantrolene may be isoform specific (less effective on RyR2), Ca2+-dependent (more effective at a lower Ca2+ concentration), and temperature-dependent (more effective at 37°C than at 25°C). 

The skeletal muscle relaxants are contraindicated in patients with known hypersensitivity. Baclofen is contraindicated in skeletal muscle spasms caused by rheumatic disorders. Carisoprodol is contraindicated in patients with a known hypersensitivity to meprobamate. Cyclobenzaprine is contraindicated in patients with a recent myocardial infarction, cardiac conduction disorders, and hyperthyroidism, hi addition, cyclobenzaprine is contraindicated within 14 days of the administration of a monoamine oxidase inhibitor. Oral dantrolene is contraindicated in patients with active hepatic disease and muscle spasm caused by rheumatic disorders and during lactation. See Chapter 30 for information on diazepam. 

Dantrolene is the mainstay of MH treatment. It has long been available for the treatment of muscle spasm in cerebral palsy and similar diseases. It is a hydantoin derivative that was first synthesized in 1967, and reported to be effective in the treatment of porcine MH in 1975. Also in 1975, dantrolene was shown to be more effective than procainamide in the treatment of human MH, which until that time was the drug of choice. However, the intravenous preparation was not made available until November 1979. It significantly lowered mortality. The half-life of dantrolene is estimated to be 6-8 hr. Dantrolene s primary mode of action is the reduction in calcium release by the sarcoplasmic reticulum. Dantrolene also exerts a primary antiarrhythmic effect by increasing atrial and ventricular refractory periods. Side effects of dentrolene include hepatotoxicity, muscle weakness, ataxia, blurred vision, slurred speech, nausea, and vomiting. Dantrolene is not contraindicated in pregnancy, but it does cross into breast milk and its effect on the neonate is unknown. 

Dantrolene should be repeated after 5—8 hr. Bicarbonate, procaine amide, and other drugs should be repeated as needed. Treatment of disseminated intravascular coagulation is symptomatic. Early diagnosis and treatment ofMH is essential. After effective treatment, the patient should be watched closely in the intensive care unit for recurrence of MH, myoglobinuric renal failure, disseminated intravascular coagulation, muscle weakness, and electrolyte imbalance. 

The pretreatment of MH-susceptible patients with oral or intravenous dantrolene prior to surgery in order to avoid a crisis is controversial. Most physicians do not recommend prophylactic pretreatment except in patients who have had a previously documented episode. However, if pretreatment is desired, it is recommended that therapy be begun with intravenous dantrolene in a dose of 2 mg/Kg just prior to induction of anesthesia. This prevents the uncertainty of predictive blood values associated with the use of the oral route. The adverse effects of intravenous dantrolene prophylaxis include phlebitis and tissue necrosis. Patients who receive prophylactic treatment with oral dantrolene often complain of incapacitation, gastrointestinal irritation, prolonged drowsiness, and clinically significant respiratory muscle weakness. 

C5H4O2 98-01-1) see Azimilide hydrochloride Dantrolene Piperidolate furfuryl alcohol... 

Ricaurte GA, McCann UD, Szabo Z, et al Toxicodynamics and long-term toxicity of the recreational drug 3,4-methylenedioxy-methamphetamine (MDMA, Ecstasy ). Toxicol Lett 112-113 143-146, 2000 Robinson TN, Killen JD, Taylor CB, et al Perspectives on adolescent substance use a defined population study. JAMA 258 2072-2076, 1987 Rubinstein JS Abuse of antiparkinson drugs feigning of extrapyramidal symptoms to obtain trihexyphenidyl. JAMA 239 2365, 1978 Rumack BH (ed) LSD, in Poisindex, Vol 54. Denver, CO, Micromedex, 1987 Rusyniak DE, Banks ML, Mills EM, et al Dantrolene use in 3,4-methylenedioxymethamphetamine ( ecstasy )-medicated hyperthermia (letter). Anesthesiology 10 263, 2004... 

Second-line Dantrolene Direct inhibitor of muscle contraction by decreasing the release of calcium from skeletal muscle sarcoplasmic reticulum 25 mg orally daily, increase to 25 mg 3-4 times daily, then increase by 25 mg every 4-7 days to a maximum of 400 mg/day... 

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. 

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