Fatal suicidal poisoning with antituberculosis agents with ST elevation and acute coronary syndrome symptoms--a case report.

A 19-years old, previously healthy male, ingested the higher amount of rifampicin, isoniazyd, pyrazinamide, ketoprofene and alcohol. Within less than 20 hours he developed dyspnoe, pruritus, red man syndrome, and ECG changes suggesting acute coronary syndrome appeared - ST interval elevation. In the next few hours chest pain appeared and troponin I concentration was elevated (13.54 ng/ml). The performed echocardiography revealed global hypokinesis with the decreased left ventricular ejection fraction (approx. 30%). There was no significant pathological changes in coronarography, except for slowed blood flow. Further patient developed cardiogenic shock, pulmonary oedema and died within 32 hours from medication overdose.

[Noncardiogenic pulmonary edema in the course of poisoning with clozapine, ketoprofen and thiethylperazine]. / Niekardiogenny obrzek pluc w przebiegu zatrucia klozapina, ketoprofenem i tietylperazyna.

Pulmonary edema is a severe, potentially fatal clinical condition. It happens, when interstitial fluid is accumulating in the alveoli, impeding proper gas exchange. Typically we distinguish cardiogenic and noncardiogenic pulmonary edema. The article describes the case of severe pulmonary edema, which occurred in a young woman, free of cardiac diseases, about 30 hours after a suicidal drug poisoning (clozapine, ketoprofen, thiethylperazine). Both clozapine and ketoprofen intoxication, may be severe. Complications in these poisonings affect not only the central nervous system, but also the circulatory or respiratory system and may even occur several hours after the overdose of these drugs. The study considered the causes and possible mechanisms of pulmonary edema in poisoning with these drugs.

Toxicity of non-steroidal anti-inflammatory drugs to Gyps vultures: a new threat from ketoprofen.

Three Gyps vulture species are on the brink of extinction in South Asia owing to the veterinary non-steroidal anti-inflammatory drug (NSAID) diclofenac. Carcasses of domesticated ungulates are the main food source for Asia's vultures and birds die from kidney failure after consuming diclofenac-contaminated tissues. Here, we report on the safety testing of the NSAID ketoprofen, which was not reported to cause mortality in clinical treatment of scavenging birds and is rapidly eliminated from livestock tissues. Safety testing was undertaken using captive non-releasable Cape griffon vultures (Gyps coprotheres) and wild-caught African white-backed vultures (G. africanus), both previously identified as susceptible to diclofenac and suitable surrogates. Ketoprofen doses ranged from 0.5 to 5 mg kg(-1) vulture body weight, based upon recommended veterinary guidelines and maximum levels of exposure for wild vultures (estimated as 1.54 mg kg(-1)). Doses were administered by oral gavage or through feeding tissues from cattle dosed with ketoprofen at 6 mg kg(-1) cattle body weight, before slaughter. Mortalities occurred at dose levels of 1.5 and 5 mg kg(-1) vulture body weight (within the range recommended for clinical treatment) with the same clinical signs as observed for diclofenac. Surveys of livestock carcasses in India indicate that toxic levels of residual ketoprofen are already present in vulture food supplies. Consequently, we strongly recommend that ketoprofen is not used for veterinary treatment of livestock in Asia and in other regions of the world where vultures access livestock carcasses. The only alternative to diclofenac that should be promoted as safe for vultures is the NSAID meloxicam.

[Two complex suicidal poisonings with drugs and their medicolegal aspects]. / Dwa kompleksowe samobójcze zatrucia lekami w aspekcie orzecznictwa sadowo-lekarskiego.

The main subject of the study was a toxicological investigation of biological specimens coming from two cases of intoxication with mixture of drugs. Two young people decided to commit suicide by the use of mixture of drugs mainly analgesic in approximately equal doses. For one person the dose of drugs administered turned out to be fatal while second person survived with the symptoms of acute intoxication. The analysis carried out with the use of liquid chromatographic method with mass detection (HPLC/MS) confirmed the presence of mixture of drugs in blood of living person and in postmortem specimens of the victim in significant concentrations. The toxicological findings have delivered information for discussion in medico-legal and ethical aspects.

Mechanisms involved in the attenuation of intestinal toxicity induced by (S)-(+)-ketoprofen in re-fed rats.

In addition to suppression of prostaglandins synthesis a number of factors have been implicated in nonsteroidal antiinflammatory drugs (NSAIDs) enteropathy, including oxygen radical-dependent microvascular injuries, depletion of glutathione, and food. Inflammatory cytokines such as tumor necrosis factor-alpha regulate endothelial adhesion molecules expression and promote vascular neutrophil adherence. Racemic ketoprofen is a potent NSAID with a chiral structure existing in two enantiomeric forms. Its therapeutic effects reside almost exclusively in the (S)-(+) isomer nevertheless the potential contribution to side effects of the (R)-(-) isomer cannot be ignored. The aims of this study were to explore the role of prostaglandins depletion, tumor necrosis factor-alpha production, and glutathione homeostasis in the comparative pathogenesis of intestinal injury induced by racemic-ketoprofen and its enantiomers in re-fed rats. Racemic ketoprofen and (R)-(-)-ketoprofen dose-dependently caused similar and multiple lesions in the mid-jejunum significantly higher than those observed with (S)-(+)-ketoprofen. All the treatments significantly decreased prostaglandins content. A significant increase of tumor necrosis factor-alpha production and decreases in glutathione levels and glutathione reductase activity after treatment of the racemate and (R)-(-)-ketoprofen, were observed whereas the (S)-(+)-isomer did not change these parameters. In conclusion, (S)-(+)-ketoprofen possesses a better intestinal toxicity profile than the racemate and its (R)-(-)-isomer. Despite inhibiting cyclooxygenase activity, the attenuation of (S)-(+)-ketoprofen-induced intestinal toxicity could be correlated with a reduced oxidative damage characterized not only by a lack of changes in glutathione reductase activity and glutathione levels but also by an absence of up-regulation of tumor necrosis factor-alpha production in intestinal mucosa.