New epidemiological study in malignant hyperthermia reinforces the effectiveness of Dantrium® in reducing fatal anaesthetic reaction

Main Category: Pain / Anesthetics
Also Included In: Clinical Trials / Drug Trials;  Surgery
Article Date: 20 Aug 2013 - 1:00 PDT Current ratings for:
New epidemiological study in malignant hyperthermia reinforces the effectiveness of Dantrium® in reducing fatal anaesthetic reaction

For the first time, a new Canadian epidemiologic study reveals that a 15.5 per cent incidence of adverse anaesthetic reactions is triggered by succinylcholine alone. In line with previous findings, the study also further underlines that early recognition and prompt administration of dantrolene intravenous are critical for patient survival and reduction of complications.[1]

The study reviews one hundred twenty-nine proband* survivors of adverse anaesthetic reactions, whose malignant hyperthermia susceptible status was confirmed by caffeine-halothane contracture testing. Among the findings are lower than expected complication rates in anaesthetising facilities using either succinylcholine or volatile anaesthetic drugs.

Importantly, it also reports that dantrolene reduced the incidence of complications (e.g. renal and cardiac dysfunction, disseminated intravascular coagulation) in these patients. If given between 10 and 19 minutes after the start of malignant hyperthermia, the complication rate is under 20 per cent. An escalating relationship between time to administration was identified, showing that complications can reach 100 per cent when the administration of dantrolene was delayed beyond 50 minutes.

This study is worth noting because it also highlights how having dantrolene readily available can reduce the morbidity and mortality caused by malignant hyperthermia and therefore suggests the importance of reviewing stock levels in hospitals.

The incidence of malignant hyperthermia varies greatly among different populations due to genetic diversity. Recent data suggest the genetic predisposition may be as prevalent as 1 in 3,000 people.[2]

Dr Gunilla Islander, Department of Anaesthesia, Lund hospital, Sweden commented; "These new data are very important as they emphasize that survival from a malignant hyperthermia crisis, a rare condition, is highly dependent on early recognition and prompt action, and that the rapid use of dantrolene can ensure patient survival".

In Europe, DANTRIUM® (dantrolene) is commercialised by Norgine B.V. In December 2012, Norgine B.V. with the owners of SpePharm Holding B.V., created a joint venture company, SpePharm AG, which acquired the specialist hospital products of SpePharm Holding B.V. - DANTRIUM® IV, DANTRIUM® capsules, SAVENE®, XEROTIN® and PROTHER®.

About Malignant Hyperthermia
Malignant hyperthermia is an inherited, rare, life-threatening condition. Triggers for malignant hyperthermia include skeletal muscle relaxants such as succinylcholine and certain volatile anaesthetic gasses, one example of which is halothane.

Early recognition of a pending malignant hyperthermia crisis and immediate treatment are essential for the patient's survival.

About dantrolene (DANTRIUM®)
Dantrolene IV is indicated for malignant hyperthermia and acts peripherally to lower the intracellular calcium concentration in the skeletal muscle.

This occurs by decreasing the release of calcium ions from the sarcoplasmic reticulum and inhibiting the influx of calcium into the myoplasm. Therefore, it effectively slows or stops the cycle of malignant hyperthermia.

Dantrolene oral capsule(s) is a muscle relaxant indicated for chronic spasticity. It is the only agent that acts directly at the level of the skeletal muscle and it therefore has a unique place among the muscle relaxants prescribed.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
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*Malignant hyperthermia often has a familial genetic lineage (autosomal dominant). In this study probands are individuals who presented with the first known cases of malignant hyperthermia in their families. These subjects then had a Caffeine-Halothane Contracture Test, a gold-standard test used widely in North America to confirm susceptibility to malignant hyperthermia.

[1] Sheila Riazi et al. Malignant Hyperthermia in Canada: Characteristics of Index Anesthetics in 129 Malignant Hyperthermia Susceptible Probands. Anesth Analg. 2013 Jul 10. [Epub ahead of print], doi: 10.1213/?ANE.0b013e3182937d8b

[2] Glahn et al. Recognizing and managing a malignant hyperthermia crisis: guidelines from the European Malignant Hyperthermia Group. British Journal of Anaesthesia 105 (4): 417-20 (2010), doi: 10.1093/bja/aeq243

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Manufacture of pharmaceuticals and other compounds could be streamlined by chemical reaction

Main Category: Pharma Industry / Biotech Industry
Article Date: 25 Jul 2013 - 0:00 PDT Current ratings for:
Manufacture of pharmaceuticals and other compounds could be streamlined by chemical reaction

Researchers at The University of Texas at Austin have discovered a new chemical reaction that has the potential to lower the cost and streamline the manufacture of compounds ranging from agricultural chemicals to pharmaceutical drugs.

The reaction resolves a long-standing challenge in organic chemistry in creating phenolic compounds from aromatic hydrocarbons quickly and cheaply.

Phenolic compounds, or phenols, are broadly used as disinfectants, fungicides and drugs to treat many ailments such as Parkinson's disease. Creating a phenol seems deceptively simple. All it requires is replacing a hydrogen molecule on an aromatic hydrocarbon with an oxygen molecule.

"This is a chemical transformation that is underdeveloped and at the same time pivotal in the production of many chemicals important to life as we know it," said Dionicio Siegel, an assistant professor of chemistry in the College of Natural Sciences at The University of Texas at Austin.

The secret that Siegel and his colleagues discovered is a substance called phthaloyl peroxide. This chemical was studied in the late 1950s and early 1960s, but it has been largely ignored during the intervening years.

The scientists were conducting basic studies on phthaloyl peroxide, building on previous research, and decided to use it to tackle the age-old problem of transforming aromatic hydrocarbons into phenols.

The advantage to using phthaloyl peroxide is that the reaction does not require the use of acids or catalysts to work, and it can add oxygen to a wide variety of starting materials.

"There are no special conditions," said Siegel. "You just combine the reagents, mix them and go. It's very simple and straight forward."

The paper describing this discovery was published recently in Nature.

The new process can be applied to other problems in organic chemistry. One particular area of interest is creating metabolites to drugs. Metabolites are the products left after the body finishes breaking down, or metabolizing, a substance. When testing drugs, scientists need to take into account not just how the drug itself reacts in the body, but also how the metabolites react.

"We've had a long-standing interest in accessing metabolites of drugs or compounds that are used in biological systems," said Siegel. "Just as it's important that the drug doesn't have deleterious side effects, it's equally important that the metabolite doesn't have an effect. You need to be able to test them, and there's not really a direct way to access metabolites other than using liver microsomes, and that's not efficient and it doesn't always work."

Another area where Siegel and his colleagues are applying what they have learned is in developing even more reactive agents that will expand the scope of chemicals that can be transformed. Siegel hopes to get this new process into the hands of others quickly. He is working with chemical supply companies to market the phthaloyl peroxide compound and/or the precursors and make it available to people in research and the pharmaceutical industry.

"It hasn't even come out yet," said Siegel, "but there are a lot of people that are already picking up the technique and working on it."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
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Siegel is a co-author on the paper, along with his graduate student, Changxia Yuan, and two undergraduate researchers, Taylor Hernandez and Adrian Berriochoa. Two other co-authors, Kendall Houk and Yong Liang, are from the University of California, Los Angeles.

University of Texas at Austin

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