In malignant hyperthermia

Robinson R, Carpenter D, Shaw MA et al (2006) Mutations in RYR1 in malignant hyperthermia and central core disease. Hum Mutat 27 977-989... 

Moore, D.C. (1986). Ester or amide local anesthetics in malignant hyperthermia— Who knows Anesthesiology 54, 294-296. 

Fill, M., Stefani, E., Nelson, T.E (1991). Abnormal sarcoplasmic reticulum Ca release channels in malignant hyperthermia skeletal muscle. Biophys. J. 59, 1085-1090. 

In malignant hyperthermia (MFI), muscle rigidity and fever develop rapidly, following exposure to inhalation anesthetic agents or succinylcholine. The gene for this disorder was recently described. Other differential diagnostic considerations include ... 

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. 

Lyfenko, A., Goonasekera, S. A., and Dirksen RT (2004). Dynamic Alterations in Myoplasmic Ca2+ in Malignant Hyperthermia and Central Core Disease. Biochem. Biophys. Res. Commun 322(4) 1256-66. 

McCarthy, T. V., Quane, K. A., and Lynch, P. J. (2000). Ryanodine Receptor Mutations in Malignant Hyperthermia and Central Core Disease. Hum Mutat 15(5) 410-7. 

Oyamada, H., Oguchi, K., Saitoh, N., Yamazawa, T., Hirose, K., Kawana, Y., Wakatsuki, K., Tagami, M., Hanaoka, K., Endo, M., and lino, M. (2002). Novel Mutations in C-Terminal Channel Region of the Ryanodine Receptor in Malignant Hyperthermia Patients. Jpn J Pharmacol 88(2) 159-66. 

Ward A, Chaffman MO, Sorkin EM. Dantrolene. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in malignant hyperthermia, the neuroleptic mahgnant syndrome and an update of its use in muscle spasticity. Drugs 1986 32(2) 130-68. 

Ranklev E, Henriksson KG, Fletcher R, Germundsson K, Oldfors A, Kalimo H. Clinical and muscle biopsy findings in malignant hyperthermia susceptibility. Acta Neurol Scand 1986 74(6) 452-9. 

Some diseases are so rare that the prospects of conducting a clinical trial are remote. It is unlikely that enough patients could ever be collected at any reasonably small number of study sites for any useful randomization. These diseases may be found in the literature as case reports. In these cases, probably the best that can be accomplished is to collect and retrospectively analyze as many such cases as possible. If the drug of interest has been used in a sufficient number of patients, then retrospective risk ratios for benefit and harm can be calculated. This may be the strongest evidence that can ever be collected about a particular drug under these rare conditions, albeit never as strong as a controlled clinical trial. One example is the effectiveness of dantrolene in malignant hyperthermia (Strazis and Fox, 1993). 

Blocks ANS ganglia and releases histamine ->4- BP, may cause bronchial secretion and bron-chospasm. Implicated in malignant hyperthermia. 

Answer D. The pharmacologic action common to both morphine and D-tubocurarine is the release of histamine from mast cells, causing vasodilation. Morphine increases, but D-tubocurarine (via ganglion blockade) decreases, bladder tone. When used in combination with inhalational anesthetics (e.g., halothane), D-tubocurarine has been implicated in malignant hyperthermia. Morphine relaxes the uterus, but D-tubocurarine has no effects on smooth muscle neurotransmission. 

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