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)

Dantrolene sodium or dantrolene1 is 1([5-(nitrophenyl)furfurylidend] amino) hydantoin sodium hydrate. It is indicated for use in chronic disorders characterised by skeletal muscle spasticity, such as spinal cord injury, stroke, cerebral palsy and multiple sclerosis. Dantrolene is believed to act directly on the contractile mechanism of skeletal muscle to decrease the force of contraction in the absence of any demonstrated effects on neural pathways, on the neuromuscular junction, or on the excitable properties of the muscle fibre membranes. Controlled trials have demonstrated that dantrolene is superior to placebo in adults or children with spasticity from various causes, as evidenced by clinical assessments of disability and daily activities, and by muscle and reflex responses to mechanical and electrical stimulation. It is somewhat less effective in patients with multiple sclerosis than in those with spasticity from other causes. There has been a general clinical impression in controlled trials that dantrolene caused less sedation than would have been expected from therapeutically comparable doses of diazepam. In 2 controlled trials, there was no significant difference between dantrolene and diazepam in terms of reductions in spasticity, clonus, and hyperreflexia, but side-effects such as drowsiness and inco-ordination occurred significantly more frequently on diazepam. Long-term studies have indicated continuing benefit for patients taking dantrolene, though the incidence of side-effects has often been high and there has been a suggestion of exacerbation of seizures in children with cerebral palsy. Dantrolene may be of value in the medical treatment of spasm of the external urethral sphincter due to neurological and non-neurological disease, and animal studies suggest a potential use in the management of malignant hyperpyrexia. Chemical evidence of liver dysfunction may occur in 0.7 to 1% of patients on long-term treatment with dantrolene, with symptomatic hepatitis in 0.35 to 0.5% and fatal hepatitis in 0.1 to 0.2%. The drug commonly causes transient drowsiness, dizziness, weakness, general malaise, fatigue and diarrhoea at the start of therapy. Muscle weakness may be the principal limiting side-effect in ambulant patients, particularly in those with multiple sclerosis, and therapy could be hazardous in patients with pre-existing bulbar or respiratory weakness. The dosage of dantrolene has been fixed in most controlled trials, though long-term studies have indicated the need for individualisation of dosage. The initial dose is usually 25mg once daily, increasing to 25mg two, three or four times daily, and then by increments of 25mg up to as high as 100mg two, three or four times daily. The lowest dose compatible with optimal response is recommended.
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PMID:Dantrolene sodium: a review of its pharmacological properties and therapeutic efficacy in spasticity. 31 89

All halothane vaporizers tested for leakage when turned off, leaked significant amounts of halothane and this may represent a hazard to patients liable to develop halothane hepatitis or malignant hyperpyrexia. The hazard from leaking vaporizers may be reduced considerably by the use of well-designed bypass units. Circuit contamination by halothane may still result from such sources as neoprene seals around flowmeters, breathing bags and anaesthetic hose which have had previous contact with halothane vapour, whether or not an apparatus is in use. The hazard from contaminated hoses and bags may be reduced considerably by washing and then hanging in a halothane-free atmosphere for a day. The hazard from contamined rubber or plastic components of the anaesthetic machine can be eliminated only by using one apparatus without the vaporizers having been attached at any time during its working life. Similarly, hazards may arise from trichloroethylene vaporizers and from circuit components contaminated with trichloroethylene.
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PMID:Inadvertent contamination of anaesthetic circuits with halothane. 88 61

This review deals with the adverse reactions associated with general anaesthetic agents in current use. These reactions fall into 2 categories; those which are more common, predictable and often closely related, and those which are rare, unpredictable and carry a high mortality. Both inhalational and intravenous anaesthetic agents affect the central nervous and cardio-respiratory systems in a dose-related manner. Neuronal inhibition results in decreasing levels of consciousness and depression of the medullary vital centres which can lead to cardiorespiratory failure. Both groups of agents have some depressant effect on the myocardium and vascular smooth muscle leading to a fall in cardiac output and hypotension. Centrally-mediated respiratory depression is common to both groups and the inhalational agents have a direct effect on lung physiology. The most important idiosyncratic reactions to the volatile agents are malignant hyperpyrexia and 'halothane hepatitis'. Malignant hyperpyrexia has an incidence of 1:12,000 with a mortality of about 24%. It is triggered most often by halothane together with suxamethonium. Post halothane hepatic necrosis is rare. Evidence points to 2 distinct syndromes; direct toxicity from the products of reductive metabolism, and a more serious illness, immunologically mediated via haptens formed by liver proteins and the products of oxidative metabolism. Prolonged nitrous oxide exposure can cause bone marrow depression and life-threatening pressure effects by expansion of air-filled spaces within the body. The idiosyncratic reactions to the intravenous agents include anaphylactoid reactions (which are rare) and triggering of acute porphyria. Etomidate is immunologically 'clean', but it inhibits cortisol synthesis.
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PMID:Adverse effects of general anaesthetics. 141 99

A comparative study of two patients, one affected by haemorrhagic shock and encephalopathy (HSE) and the other by heatstroke is reported. Both presented shock, disseminated intravascular coagulation, neurological damage and hepatopathy. A lowered alpha 1-antitrypsin concentration as well as a slightly increased circulating immune complexes and complement consumption were observed in the HSE patient but not in the heatstroke one. In both, cultures for bacteria were negative, the viral serology was non-specific and hepatitis A and B studies were negative. HSE patient died. A possible relationship between HSE, heatstroke, malignant hyperthermia and halothane hepatitis is postulated. Fever, potentially hepatotoxic drugs or unknown agents (HSE) might trigger this clinical picture.
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PMID:[Hemorrhagic shock and encephalopathy. Its possible relation with heat stroke]. 407 88

For the past 25 years, halothane has been the primary anesthetic agent at Children's Hospital, Columbus, Ohio. To confirm our impression that adverse reactions to halothane are rarely a problem in children, we examined the records of 200,311 cases conducted with halothane from June 1, 1958, through May 31, 1983. Life-threatening complications due to side effects were identified in fifteen patients, and could be grouped into three areas: hepatitis (one), malignant hyperthermia (ten), and cardiac arrhythmias (four). No child died or sustained permanent sequelae. In eleven instances, other drugs (succinylcholine, atropine, cocaine, and epinephrine) possibly contributed to the adverse reactions.
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PMID:Halothane and children: the first quarter century. 646 80

The methods of gathering information to determine the safety of anesthesia and to establish the risk of mortality and morbidity include anecdotal tales, in-hospital audit and peer review, reports to medical protective societies, retrospective studies, reviews of specific problems and prospective studies. All these methods have limitations and, in particular, do not readily differentiate the anesthetic from the surgical contributions. However, it appears that over the past 30 years the risk of death directly attributable to anesthesia has decreased from 1 in 2680 to about 1 in 10 000. The main causes of death are faulty anesthetic techniques due to human error, drug overdose, coexistent disease and failure of immediate postoperative care. Equipment failure, poor preoperative assessment, halothane-associated hepatitis and malignant hyperthermia, although often cited in the literature, are rarely the cause of problems associated with anesthesia.
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PMID:Anesthesia in 1984: how safe is it? 646 15

Seventy-four responses were received from a questionnaire which had been mailed to 91 bone marrow transplantation institutes throughout Japan to assess the activity of bone marrow transplantation and complications in bone marrow donors. A total of 2329 bone marrow harvests, performed from 1688 adult donors and 641 child donors for allogeneic or syngeneic transplantation up to August 1992, were available for study. Analyses of the responses showed slight diversity regarding the marrow harvesting preparation and methods of the different bone marrow programs. The resulting perioperative complications were principally caused by anesthesia: 73 episodes of hypotension including one death 18 months later, seven of arrhythmia, one of respiratory arrest, three of mental confusion, one of asthma, one of malignant hyperthermia, one tooth injury and one broken aspiration needle. The postoperative complications were chiefly caused by marrow aspiration per se: 731 episodes of transient fever, 26 of long-lasting pain or discomfort, 10 episodes of liver dysfunction including two cases of non-A, non-B hepatitis, four cases of infection, one episode of hypotension, one of dysuria and one case of keloid formation. The study further revealed that the frequency of complications was lower in child donors than in adult donors.
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PMID:[Complications of marrow harvesting for transplantation]. 813 99

Side effects in the short term Recreational use of Ecstasy (3,4-methylenedioxymethamphetamine or MDMA), a synthetic drug, has considerably increased over the last decade. Since its appearance it is associated with the rave culture, but its use has spread to other social settings. The drug produces euphoria and empathy, but can lead to side effects, notably acute, potentially lethal, toxicity (malignant hyperthermia and/or hepatitis). Neurotoxicity in the long-term Moreover, MDMA has been shown to induce long-term deleterious effects and provoke neurotoxic affecting the serotoninergic system. However, the psychopathological consequences of such neurotoxicity are still controversial, particularly since many ecstasy consumers are multi-drug users. A complex pharmacological profile The mechanism of action of MDMA involves various neurobiological systems (serotonin, dopamine, noradrenalin), that may all interact.
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PMID:[Acute and long-term effects of ecstasy]. 1561 73

The phenylalkylamine derivatives, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy, XTC, Adam), 3,4-methylenedioxyethamphetamine (MDEA, MDE, Eve), and 3,4-methylenedioxyamphetamine (MDA), are psychostimulants with hallucinogenic properties. MDA is also a metabolite of both MDMA and MDEA. These drugs are ring-substituted amphetamine derivatives that produce hallucinogenic, entactogenic ('love drug'), and stimulating effects. MDMA was initially developed as an appetite suppressant, however, its use as a therapeutic drug has been very limited. Because of its effects as a hallucinogenic psychostimulant with relatively low toxicity, it has emerged over the last two decades as a common recreational psychostimulant or 'club drug' at 'raves'. MDMA, MDEA, and MDA are often referred to as 'rave' or 'designer' drugs. They are produced in clandestine laboratories and have an increasing presence on the illicit drug market worldwide. Significant adverse health effects have been reported that include: serotonin neurotoxicity, severe psychiatric disorders, renal failure, malignant hyperthermia, hepatitis, rhabdomyolysis, and disseminated intravascular coagulation. A number of fatal outcomes associated with severe MDMA intoxication have been reported.
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PMID:Measurement of 3,4-MDMA and related amines in diagnostic and forensic laboratories. 1591 45