Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dantrolene sodium acts primarily by affecting calcium flux across the sarcoplasmic reticulum of skeletal muscle. Recently, dantrolene has been used very successfully in the treatment of several rare hypercatabolic syndromes which have previously been associated with high mortality rates. In malignant hyperthermia, where early diagnosis and treatment usually with intravenous dantrolene in association with other supportive measures (and often subsequent dantrolene therapy) is performed, recovery is seen in virtually 100% of patients. There is a rapid resolution of hyperthermia, dysrhythmias, muscle rigidity, tachycardia, hypercapnia, mottled or cyanotic skin, and metabolic acidosis, and a slower normalisation of myoglobinuria and elevated serum creatine phosphokinase levels. In patients with family history or previous episodes of malignant hyperthermia, prophylactic treatment with dantrolene prior to anaesthesia prevents the syndrome occurring in most cases. Where malignant hyperthermia has developed patients have been successfully treated with further dantrolene therapy. Dantrolene has also been used successfully in the treatment of a few cases of heat stroke and the neuroleptic malignant syndrome--both of which have many similarities to malignant hyperthermia. Dantrolene is well established in the treatment of patients with muscle spasticity where it generally improves at least some of the components of spasticity (i.e. hyper/hypotonia, clonus, muscle cramps and spasms, resistance to stretch and flexor reflexes, articular movement, neurological and motor functions and urinary control). However, in some patients, particularly those with multiple sclerosis, dantrolene may not be effective, and in many cases muscular strength may diminish. Long term dantrolene therapy has been associated with hepatic toxicity and may cause problems in patients treated for disorders of muscle spasticity. Thus, dantrolene offers a unique advance in the therapy available for the treatment of hypercatabolic disorders and is also useful in the treatment of muscle spasticity of various aetiology.
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PMID:Dantrolene. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in malignant hyperthermia, the neuroleptic malignant syndrome and an update of its use in muscle spasticity. 352 59

Toxin-induced hyperthermic syndromes are important to consider in the differential diagnosis of patients presenting with fever and muscle rigidity. If untreated, toxin-induced hyperthermia may result in fatal hyperthermia with multisystem organ failure. All of these syndromes have at their center the disruption of normal thermogenic mechanisms, resulting in the activation of the hypothalamus and sympathetic nervous systems.The result of this thermogenic dysregulation is excess heat generation combined with impaired heat dissipation. Although many similarities exist among the clinical presentations and pathophysiologies of toxin-induced hyperthermic syndromes, important differences exist among their triggers and treatments. Serotonin syndrome typically occurs within hours of the addition ofa new serotonergic agent or the abuse of stimulants such as MDMA or methamphetamine. Treatment involves discontinuing the offending agent and administering either a central serotonergic antagonist, such as cyproheptadine or chlorpromazine, a benzodiazepine, or a combination of the two. NMS typically occurs over hours to days in a patient taking a neuroleptic agent; its recommended treatment is generally the combination of a central dopamine agonist, bromocriptine or L-dopa, and dantrolene. In those patients in whom it is difficult to differentiate between serotonin and neuroleptic malignant syndromes, the physical examination may be helpful:clonus and hyperreflexia are more suggestive of serotonin syndrome,whereas lead-pipe rigidity is suggestive of NMS. In patients in whom serotonin syndrome and NMS cannot be differentiated, benzodiazepines represent the safest therapeutic option. MH presents rapidly with jaw rigidity, hyperthermia, and hypercarbia. Although it almost always occurs in the setting of surgical anesthesia, cases have occurred in susceptible individuals during exertion. The treatment of MH involves the use of dantrolene. Future improvements in understanding the pathophysiology and clinical presentations of these syndromes will undoubtedly result in earlier recognition and better treatment strategies.
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PMID:Toxin-induced hyperthermic syndromes. 1622 63