Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024591 (malignant hyperthermia)
 2,353 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Procaine has been advocated in the treatment of malignant hyperpyrexia, whereas lignocaine has been shown to worsen the condition. Using muscle from patients susceptible to malignant hyperpyrexia in vitro, it has been demonstrated that muscle contracture can occur with procaine on its own, and in one patient the halothane-induced contracture was potentiated by procaine. In other patients the concentration of procaine required to abolish the halothane-induced contracture was markedly above the clinical dose range. In a study of lignociane and procaine on a caffeinated rat muscle (a suggested model for malignant hyperpyrexia) no significant difference was found in the ability of these local anaesthetics to alter resting tension of halothane-treated muscle; with both drugs the resting tension rose in a dose-related manner. The use of procaine as the drug of first choice in patients with malignant hyperpyrexia is challenged.
 ...
PMID:An evaluation of procaine in the treatment of malignant hyperpyrexia. 114 70

Procaine caused respiratory arrest in halothane-anaesthetized normal Landrace pigs at a dose of 4,2 - 8,2 mg/kg. In some cases death due to respiratory failure occurred after giving 10 - 13 mg/kg. Because of its toxicity in pigs procaine is unsuitable for treating the porcine malignant hyperthermia syndrome.
 ...
PMID:On the toxicity of procaine for pigs. 121 6

Halothane itself (1--3 vol percent) produced no significant changes in either Td or dT/dt max of the isolated hemidiaphragm during direct electrical stimulation. On the other hand, halothane significantly potentiated the effect of aminophylline on the resting tension of the muscle, both in a resting non-stimulated muscle and during direct electrical stimulation. Diethyl-ether did not affect the action of aminophylline on the resting tension. The interaction between halothane and aminophylline can be taken as a model for malignant hyperpyrexia. Procaine regularly produced further potentiation of the halothane-aminophylline interaction. There was no halothane-aminophylline interaction in a calcium-free medium. Verapamil was found to potentiate the halothane-aminophylline interaction, whereas di-Na-EDTA depressed it. Halothane did not significantly affect the actions of isoprenaline and adrenaline on Td and dT/dt max during direct electrical stimulation. So far, there is no obvious molecular basis for the action of halothane, but the available evidence indicates that its action is taking place both on the cell membrane and inside the cell, probably by blocking the reaccumulation of calcium in the sarcoplasmic reticulum and thus increasing the amount of free calcium in the cell.
 ...
PMID:Interaction of halothane and aminophylline on the isolated hemidiaphragm of the rat. 676 97

Malignant hyperthermia, a relatively recently described entity, is a little-understood disease process usually manifesting as operative or postoperative hyperpyrexia in association with a hypermetabolic state. Specific therapy with procaine (Novocaine) and more recently with a muscle relaxant, dantrolene sodium (Dantrium), has shown itself to be life-saving, and currently diagnosis can be made by muscle biopsy in patients from affected pedigrees. Malignant hyperthermia is a risk in all general anesthetic procedures, particularly squint and ptosis repair, and may even be a consideration with local anesthesia.
 ...
PMID:Malignant hyperthermia. Considerations for the ophthalmologist. 724 23

One hundred and fifty paired extensor long digital muscles were excised from Wistar rats and each muscle was prepared in Krebs-Ringer's solution (K-R solution) then gassed with a mixture of 95% O2-5% CO2. The medium for the control muscles was replaced with K-R solution containing 10(-6) M ryanodine and that for the experimental muscles was replaced with medium containing 10(-6) M ryanodine and local anesthetic (LA) (procaine, tetracaine, benzocaine, lidocaine or bupivacaine at various concentration). Isometric contracture tension was recorded throughout the experiment. The ratios of the maximal contracture tension (C-ratio) and the elapsed time (T-ratio) of the muscles treated with LA compared to those of control muscles were calculated. Tetracaine (0.125-1.0 mM) specifically reduced the C-ratio. Procaine (0.5-1.0 mM) and tetracaine (10-60 microM) increased the T-ratio. Procaine (8-16 mM), benzocaine (4-8 mM), lidocaine (0.5-4 mM) and bupivacaine (0.125-1 mM) reduced the T-ratio. The influences of LAs on ryanodine-induced contracture could be explained in terms of their effects on the Ca(2+)-induced Ca2+ release mechanism, direct Ca2+ efflux from sarcoplasmic reticulum (SR), activity of Ca2+ uptake into SR and ryanodine-receptor binding. The complexity of LA effects on ryanodine-induced contracture will affect the results of ryanodine contracture tests for malignant hyperthermia when the muscle specimen is excised under local anesthesia.
 ...
PMID:[The influences of local anesthetics on ryanodine-induced contracture in rat skeletal muscle]. 774 90