Vergiftung durch Alkaloide von Veratrum album in Baldriantinktur

Ohne Zusammenfassung     

A neurally mediated inotropic effect of veratridine and cevadine on isolated guinea-pig papillary muscle

Summary The positive inotropic effect of veratridine and cevadine was investigated in the isolated, isometrically contracting guinea-pig papillary muscle. The increase of the force of the rested-state contraction, elicited after incubation of the resting muscle with veratridine or cevadine, served as a measure of the neurally mediated, sympathomimetic effect of these alkaloids. Concentrations exceeding 5 mol/l veratridine or 15 mol/l cevadine produced concentration-dependent increases of the force of the rested-state contraction. These concentrations are larger than those causing the maximum positive inotropic effect on muscles contracting continually at a rate of 1 Hz. The positive inotropic effect of 30 mol/l veratridine as manifested by the rested-state contraction was absent in the presence of 100 nmol/l tetrodotoxin and in muscles from reserpine-pretreated animals. It was significantly inhibited by 50 nmol/l (–)-propranolol, but not by the same concentration of (+)-propranolol. The effect of 30 or 60 mol/l cevadine was likewise absent in catecholamine-depleted preparations. It is concluded that the indirect inotropic effect of veratridine or cevadine, which is attributed to their noradrenaline-releasing effect on intracardiac nerves, requires higher concentrations than the direct positive inotropic effect, which is a consequence of the increased transsarcolemmal influx of Na ions into the myocardial cell.These results were communicated to the Deutsche Pharmakologische Gesellschaft (Honerjäger 1977)     

Three fatal cases of PMA and PMMA poisoning in Denmark

Paramethoxyamphetamine (PMA) and paramethoxymetamphetamine (PMMA) are methoxylated phenylethylamine derivatives with effects similar to methylenedioxymetamphetamine (MDMA) and sold as such. However, PMA and PMMA are more potent than MDMA, but have a slower onset of action, which encourages users to take more. Three fatal cases involving PMA and PMMA in Denmark in year 2000 are investigated including history, pathological, and toxicological findings. The methods used for extraction, identification, and quantitation of PMA and PMMA are described. In two of the cases, lethal postmortem blood concentrations of PMA and PMMA were determined at 3.4 and 3.3 mg/kg (case 1) and 0.78 and 0.68 mg/kg (case 3), respectively. In addition, other drugs such as MDMA, tetrahydrocannabinol, cocaine, and alcohol were involved in these cases. In the third case, death occurred four days after the ingestion of tablets containing PMA and PMMA, and therefore only low postmortem concentrations of PMA and amphetamine were detected. However, in a serum sample taken at admission to the hospital, PMA and PMMA were found, but not quantitated. It is believed that the cause of death in case 2, multiple-organ failure, was caused by overdoses of PMA and PMMA.     

Benzodiazepines and alcohol are associated with cases of fatal buprenorphine poisoning

Background  

Although buprenorphine therapy has proved to be successful in opioid maintenance treatments, the drug is also widely abused in many countries by intravenous injection or sniffing (“snorting”). In Finland, buprenorphine is the most important abused opioid causing fatal poisonings.     

Nitrate poisoning in cattle fed Chenopodium album hay

Three cows fed Chenopodium album hay died 30 min after showing ataxia, bluish-brown mucous membranes, rapid and difficult breathing, increased heart rates, tremors and coma. Brown-colored and badly coagulated blood was the prominent necropsy finding. Slight pulmonary edema was prominent and all visceral organs were hyperemic. The hay contained 2,500 ppm nitrate-nitrogen and 11 ppm nitrite nitrogen.     

Disposition of cocaine in fatal poisoning in man

A fatal case of intravenous (IV) cocaine administration is presented. Cocaine tissue concentrations (mg/kg) in descending order were: kidney, 26; spleen, 22; brain, 14; heart, 6.1; skeletal muscle, 6.1; lung, 3.4; liver, 1.6; and adipose, 1.0. Body fluid cocaine concentrations (mg/L) were: urine, 39; bile, 10; vitreous humor, 2.4; and blood, 1.8. These results are in excellent agreement with cocaine tissue distribution in the dog following IV administration and limited tissue data in previously reported cocaine fatalities in man.     

A fatal case of propranolol poisoning

Propranolol hydrochloride is a beta-adrenergic blocking drug used in a variety of clinical conditions. Overdoses can result in severe hypotensive states usually associated with bradycardia or asystole or with profound myocardial depression. We report on an 18-year-old man who ingested a massive dose of propranolol HCl in a suicide attempt. The patient was brought to the hospital in an unresponsive state within 30 minutes of ingestion. He was initially stabilized but subsequently died nine hours after the drug was ingested. Invasive monitoring during this period revealed the shock to be secondary to marked depression of his systemic vascular resistance. Cardiac rhythm and left ventricular output were maintained throughout the attempted resuscitation. This hemodynamic picture suggests that decreased systemic vascular resistance may be another mechanism of shock in significant propranolol HCl overdoses.     

Blood-pressure lowering, positive chronotropy and inotropy by the Veratrum alkaloids germidine and germerine but negative chronotropy by veratridine in mice

Germidine and germerine, the Veratrum alkaloids lowered blood pressure accompanied with positive chronotropy and inotropy in mice. Germerine was more potent than germidine in both blood-pressure lowering and positive inotropy, whereas veratridine produced negative chronotropy and positive inotropy. An acyl group (an acetyl or a 2-methylbutyroyl group) at 3-O-R¹ position and a 2-methylbutyroyl group at 15-O-R² position in germine were important to produce the positive inotropy and chronotropy. The presence of a veratroyl group at 3-O-R¹ position and a free hydroxyl group at 15-O-R² position may be essential to produce the negative chronotropy by veratridine. The positive inotropy by germidine and veratridine may be due to TTX-resistant Na⁺ channel activation.