A rare fatality attributed solely to metaxalone.

Metaxalone (Skelaxin) is a prescription medication used primarily as a centrally acting skeletal muscle relaxer and is rarely implicated in drug fatalities. We present a case study involving a relatively young decedent where metaxalone is implicated as the sole agent causing death with little in the way of confounding factors. The concentration of metaxalone in hospital admission blood was determined to be 37.4 mcg/mL. In postmortem specimens the concentrations were shown to be 13.5 mcg/mL (heart blood), 4.9 mcg/mL (vitreous humor), 69.4 mcg/g (liver) and 74.0 mcg/g (brain). Additionally a blood-to-plasma (b/p) ratio was estimated using antemortem blood and serum specimens taken at the same time on the second day following admission. The b/p ratio was calculated to be 1.4 implying a higher proportion of the drug to be found in whole blood versus plasma/serum samples, an important factor which should be taken into account when comparing blood concentrations to published therapeutic ranges determined in serum/plasma.

Serotonin syndrome associated with metaxalone overdose.

INTRODUCTION: Serotonin syndrome is a potentially life-threatening entity associated with pro-serotonergic medications in therapeutic use, in overdose, or when co-administered with other drugs. A broad range of drugs and drug combinations have been associated with serotonin syndrome. Metaxalone overdose associated with serotonin syndrome has not been previously reported. CASE REPORT: (Case 1) A 23-year-old female overdosed on tramadol and metaxalone. She developed dysautonomia, diaphoresis, lower extremity rigidity and spontaneous clonus, flaccid upper extremities, and hyperthermia 5 h after ingestion. Her course was complicated by status epilepticus. (Case 2) A 56-year-old female overdosed on metaxalone and was found unresponsive. She developed dysautonomia, lower extremity rigidity and spontaneous clonus, flaccid upper extremities, rhabdomyolysis, acute renal failure, and hyperthermia. Non-depolarizing neuromuscular blockade and cooling blankets were required to control hyperthermia in both cases. Serum metaxalone levels were markedly elevated in both cases. CONCLUSION: These are the first reported cases of metaxalone overdose associated with serotonin syndrome, which may be related to monoamine oxidase inhibition.

Adult metaxalone ingestions reported to Texas poison control centers, 2000-2006.

Few data exist on potentially adverse metaxalone (Skelaxin(R)) ingestions in adults. All metaxalone ingestions involving patients aged >or=20 years during 2000-2006 were retrieved from Texas poison control centers. Exclusion criteria were lack of follow-up or multiple substance ingestion. Cases were analyzed for selected demographic and clinical factors. Of the 142 patients, 66.2% were female. Dose ingested was reported for 61 patients. Of those cases with a reported dose, distribution by management site was 29.5% on-site, 59.0% already at/en route to health care facility, and 11.5% referred to health care facility. Final medical outcome was 'no effect' for 50.8% cases, 'minor effect' for 31.1%, and 'moderate effect' for 18.0%. The more common adverse clinical effects reported were drowsiness (27.9%), tachycardia (6.6%), agitation (6.6%), nausea (4.9%), dizziness (4.9%), slurred speech (4.9%), and tremor (4.9%). A moderate medical outcome occurred in 13.6% of ingestions of 2400 mg. Management involved a health care facility in 18.2% of ingestions of 2400 mg. This study found that adult ingestions of higher doses of metaxalone, particularly >2400 mg, were associated with more serious medical outcomes and were managed at health care facilities. This study also proposes triage guidelines for when ingestions can be safely managed at home.

Severe botulism after focal injection of botulinum toxin.

We report a 34-year-old woman who developed clinical botulism after the cosmetic use of an unapproved botulinum toxin type A. Electrophysiologic findings demonstrated complete denervation with complete electrical silence. She had a lengthy recovery but was able to ambulate by discharge.

Botulinum neurotoxin type D enables cytosolic delivery of enzymatically active cargo proteins to neurones via unfolded translocation intermediates.

Multi-domain bacterial protein toxins are being explored as potential carriers for targeted delivery of biomolecules. Previous approaches employing isolated receptor binding subunits disallow entry into the cytosol. Strategies in which catalytic domains are replaced with cargo molecules are presumably inefficient due to co-operation of domains during the endosomal translocation step. Here, we characterize a novel transport vehicle in which cargo proteins are attached to the amino terminus of the full-length botulinum neurotoxin type D (BoNT/D). The intrinsic enzymatic activity of the neurotoxin allowed quantification of the efficacy of cargo delivery to the cytosol. Dihydrofolate reductase and BoNT type A (BoNT/A) light chain (LC) were efficiently conveyed into the cytosol, whereas attachment of firefly luciferase or green fluorescent protein drastically reduced the toxicity. Luciferase and BoNT/A LC retained their catalytic activity as evidenced by luciferin conversion or SNAP-25 hydrolysis in the cytosol of synaptosomes, respectively. Conformationally stabilized dihydrofolate reductase as cargo considerably decreased the toxicity indicative for the requirement of partial unfolding of cargo protein and catalytic domain as prerequisite for efficient translocation across the endosomal membrane. Thus, enzymatically inactive clostridial neurotoxins may serve as effective, safe carriers for delivering proteins in functionally active form to the cytosol of neurones.

Using potentially life-shortening drugs in neonates and infants.

OBJECTIVE: To describe the frequency, background, and impact of decisions to give analgesic or other drugs that may, intentionally or unintentionally, shorten the life-span of severely ill neonates. SETTING: The Netherlands. DESIGN: Retrospective, cross-sectional study. PATIENTS: Questionnaires were mailed in The Netherlands to physicians reporting 338 consecutive deaths of infants under 1 yr of age from August through November 1995. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Questions were asked about medical end-of-life decisions preceding the death of the infant and about the decision-making process. Potentially life-shortening drugs, mostly opioids, were given in 37% of all deaths. The estimated effect in terms of the shortening of life was <1 wk in 72% of all patients in whom the administration of potentially life-shortening drugs had been the most important end-of-life decision. Most decisions to administer such drugs were discussed with parents and colleagues. The decisions were discussed regarding virtually all patients in whom the physician had intended to hasten death; doses of opioids tended to be larger in this group. CONCLUSIONS: The frequency with which drugs that may shorten life are administered before the death of severely ill infants confirms the important role of modern medicine in dying in neonatology. Most physicians caring for neonates feel that palliative medication may be warranted in dying infants, even if it shortens life. A distinction between intentionally ending life and providing adequate terminal care by alleviating pain or other symptoms, which is important in moral and judicial terms, is probably not easily made for some of these patients.