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

Narcots and muscle relaxants are proven causes of malignant hyperthermia. Alcohol and a large number of drugs are capable of inducing myopathic changes which resemble malignant hyperthermia. The case of a 47-year-old man is reported who presented with the clinical symptoms of maligant hyperthermia. The similarity in the course of the disturbance, the clinical and chemical findings and the changes in the morphological features of the muscle suggested that the abnormally high body temperature had been induced by psychotropic durgs in a pre-disposed patient with an history of chronic alcoholism.
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PMID:[A case of malignant hyperthermia unrelated to anaesthesia (author's transl)]. 63 2

The effects on erythrocyte fragility of two general anaesthetic agents (halothane and ethanol) and succinylcholine were examined using preparations from 13 normal and four malignant hyperthermia susceptible patients. Erythrocyte fragility was determined by the degree of haemolysis induced in solutions of decreasing osmolarity of NaCl. Halothane caused haemolysis of erythrocytes in an isoosmolar solution, being more potent at 42 degrees C than at 32 degrees C. Haemolysis produced by an hypoosmolar medium or halothane was potentiated by exogenously added phospholipase A2. Ethanol did not markedly alter the haemolysis of erythrocytes under conditions of decreasing osmolarity. Succinylcholine 10 mM did not significantly alter the susceptibility of erythrocytes to lysis by halothane. No differences in erythrocyte fragility were observed between preparations from normal and malignant hyperthermia susceptible patients under any of the conditions tested, despite the inclusion of malignant hyperthermia triggering agents in some instances. Although sampling a larger patient population might reveal slight differences between the groups, erythrocyte fragility tests do not appear to be useful in differentiating malignant hyperthermia susceptible from normal patients.
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PMID:Effects of anaesthetic agents on erythrocyte fragility: comparison of normal and malignant hyperthermia susceptible patients. 360 52

Malignant hyperthermia is an often lethal hypermetabolic crisis state precipitated by a variety of pharmacological and environmental triggers in genetically susceptible persons. The present report documents, by medical history and necropsy, a fatal malignant hyperthermic crisis in a 20-year-old man after an evening of recreational cocaine and ethanol abuse.
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PMID:Fatal malignant hyperthermia associated with recreational cocaine and ethanol abuse. 378 15

The effectivity of treatment of a dramatically progressing malignant hyperthermia with Dantrolen depends, inter alia, on the easy production and applicability of the preparation. The modification described in this article, of an intravenously injectable Dantrolen solution which contains 10.0 mg active substance in 1.0 ml of a mixture of ethanol, glycerin and water, seems to meet these conditions, as established by experimental investigation.
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PMID:[Dantrolen solution of high active substance concentration. Preliminary communication (author's transl)]. 677 58

Pharmacogenetics of cytochromes P-450. Cytochromes P-450 are a large family of enzymes found in all living species whose function is the activation of molecular oxygen which, in turn, will oxidize an organic substrate. They are divided in two groups: one including the constitutive enzymes that intervene in vital processes such as cholesterol synthesis, cholesterol transfer into steroid and sex hormones, prostaglandin synthesis, etc.; the other group including the inducible enzymes, responsible of the metabolism of exogenous substances. Their concentration increases in the presence of specific substrates, like herbicides, cigarette smoke, hydrocarbons, insecticides, etc.. Of the latter group, the genetic polymorphism of two families is described. Family I is involved in the metabolism of polycyclic aromatic hydrocarbons: an allele codifying for a low activity cytoplasmic receptor (autosomic recessive inheritance) and a high affinity one (recessive inheritance) are present. The transformations carried out by the cytochromes P-450 give origin to intermediate reactive products, epoxides, that bonding to nucleoproteins or nucleic acids, can have either toxic or carcinogenic action. Therefore, the subjects with high affinity genes have an increased risk of cancer. This phenomenon, relating to pulmonary cancer, has been demonstrated in cigarette smokers. Family II is the group of greatest pharmacogenetic and clinical interest, since it is responsible of the polymorphism of the response to different drugs, such as halothane, (malignant hyperthermia), ethanol (alcohol intolerance), nitrosamine, (cancer), debrisoquine (hypotension), spartein (excessive uterine contractions). An increased or reduced ability to metabolize specific substances is the consequence: the pharmacological effects can therefore vary very much in the two classes of carriers of different alleles. Possible future applications of these polymorphisms in clinical practice are discussed.
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PMID:[Pharmacokinetics of cytochrome P-450]. 823 56

Binge drinking of alcohol, cocaine overdose, or overexertion can lead to rhabdomyolysis characterized by elevated creatine kinase (CK) and myoglobin in the serum, myoglobinuria, and muscle tenderness. Our previous studies showed that ethanol, cocaine, and electrical stimulation enhanced the leakage of CK from isolated soleus and extensor digitorum longus (EDL) muscles of rat. Dantrolene sodium was reported to reduce the muscle damage and elevated serum CK levels in exercised rats. The present study was aimed at testing whether dantrolene can reduce the enhanced leakage of CK from isolated rat soleus and EDL muscles caused by ethanol, cocaine, and electrical stimulation. After 4-hr incubation in oxygenated physiological solution at 37 degrees C, the mean leakage of CK was 1.56 units/mg of muscle in soleus and 0.89 units/mg in EDL. Ethanol at 0.2% increased the leakage of CK by 47% (p < 0.05) in soleus and by 26% in EDL. Cocaine at 1 mM increased the leakage of CK by 55% (p < 0.05) in soleus and by 27% in EDL. Electrical stimulation at 1 Hz for 4 hr increased the mean leakage of CK by 100% (p < 0.05) in soleus and 127% (p < 0.05) in EDL. Dantrolene sodium reduced the enhanced leakage of CK caused by ethanol, cocaine, and electrical stimulation significantly in soleus and slightly in EDL. Dantrolene may involve myoplasmic free Ca2+ in these beneficial effects as in malignant hyperthermia, and may be useful in the treatment of rhabdomyolysis associated with acute alcoholic myopathy, cocaine overdose, and overexertion.
Alcohol Clin Exp Res 1997 Feb
PMID:Dantrolene sodium reduces the enhanced leakage of creatine kinase caused by ethanol, cocaine, and electrical stimulation in isolated fast and slow muscles of rat. 904 74

This paper proposed a multiple headspace single-drop microextraction (MHS-SDME) method coupled to gas chromatography with flame-ionization detection (GC-FID) for direct determination of residual solvents in solid drug product. The MHS-SDME technique is based on extrapolation to an exhaustive extraction of consecutive extractions from the same sample which eliminates the matrix effect on the quantitative analysis of solid samples. The total peak area of analyte is calculated with a beta constant which can be obtained from the slope of the linear regression that related to the peak area of each extraction and the number of extraction times. In this work, a model drug powder was chosen and the amounts of residues of two solvents, methanol and ethanol, were investigated. The factors influencing the extraction process including extraction solvent, microdrop volume, extraction time, sample amount, thermostatting temperature and incubation time were studied. 10mg of drug powder was incubated for 3 h at 140 degrees C prior to the first extraction and thermostatted for 15 min at 140 degrees C between each extraction. Extraction was carried out with 2 microL of dimethyl sulfoxide (DMSO) as the microdrop for 5 min. The features of the method were established using standard solutions. Validation of the proposed method showed good agreement with the traditional dissolution method for analysis of residual solvents in drug product. The results indicated that MHS-SDME has a great potential for the quantitative determination of residual solvents directly from the solid drug products due to its low cost, ease of operation, sensitivity, reliability and environmental protection.
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PMID:Multiple headspace single-drop microextraction coupled with gas chromatography for direct determination of residual solvents in solid drug product. 2059 2