An observational case series of dabigatran and rivaroxaban exposures reported to a poison control system.

OBJECTIVE: Characterize clinical presentations and outcomes of dabigatran and rivaroxaban exposures reported to a poison control system. METHODS: Data for cases of dabigatran and rivaroxaban exposures called into the California Poison Control System from January 2011 to July 2013 were collected. Data collected included patient demographics, type of exposure, medication, dosage, vital signs, laboratory values, interventions, outcomes, and disposition. Exclusion criteria included confirmed nonexposures or miscoded cases. RESULTS: A total of 56 cases were identified, with 7 excluded, leaving 37 dabigatran and 12 rivaroxaban cases. Children age 12 years or less accounted for 5 dabigatran and 2 rivaroxaban cases. Bleeding was reported in 15 dabigatran cases. There were 4 cases of acute self-harm overdose with dabigatran ranging from 1800 to 3900 mg. Mild bleeding was reported in only one of these overdose cases. There were 2 fatal hemorrhages in dabigatran cases, both in chronic therapeutic dosing. Bleeding was reported in 5 rivaroxaban cases, all in patients with chronic exposure; no deaths were reported. There were no adverse outcomes in pediatric patients. Coagulation parameters did not correlate well with bleeding. CONCLUSIONS: In our series, the greatest risk of adverse events was in patients chronically taking these agents, irrespective of excess dosing. Acute self-harm ingestions and accidental pediatric ingestions had few adverse effects, although massive overdose can lead to abnormal coagulation studies. It does not appear that single low-dose ingestions of either medication will lead to clinically significant bleeding. It may be possible to manage some pediatric exposures and most accidental ingestions with observation.

Toxicological detection of pholcodine in blood, urine and hair in three cases of fatal intoxication.

Pholcodine is an opioid antitussive reputed for its low toxicity and absence of addictive effect. We report three cases of pholcodine intoxication with fatal outcome. Large concentrations of pholcodine were quantified by gas chromatography coupled to mass spectrometry (GC/MS) in peripheral postmortem blood (respectively 2890 ng/mL, 979 ng/mL and 12,280 ng/mL). Segmental hair analyses by GC/MS and detected pholcodine in three 1.5-2 cm segments (38-161 ng/mg, 8.54-41.6 ng/mg, and 0.26-2.66 ng/mg, respectively). These findings underline that pholcodine can be involved in fatal poisoning and raise the question of misuse or abuse and of taking account of this drug in opioid overdose prevention policies.

The prevention by sulphydryl compounds of the toxicity in the cat of 2,6-dimethoxyphenol and its morpholinopropionyl ester.

1 Intravenous (minus)-2,6-dimethoxyphenyl-2-morpholinopropionate hydrochloride (M&B 16,573) produced anaesthesia of short duration in the mouse, rat, rabbit, cat, dog and monkey. In the cat but not in other species, a severe and usually fatal toxic reaction was seen 1-2 h after administration. 2 This toxic reaction but not the anaesthetic properties of M&B 16,573 was prevented by the intravenous administration of cysteine or N-acetylcysteine. Cysteamine or dimercaprol were ineffective. 3 Intravenous administration of 2,6-dimethoxyphenol or 2,6-dimethoxyquinol in the cat produced a response similar to the delayed toxic effects of M&B 16,573 but not preceded by anaesthesia. The toxic effects of these compounds were prevented by cysteine. 4 Intravenous 4-allyl-2,6-dimethoxyphenyl-2-morpholinopropionate hydrochloride produced anaesthesia in the cat without the delayed toxic effects seen after M&B 16,573. 5 The acute toxicity of 2,6-dimethoxyquinol in mice was reduced by the administration of cysteine or N-acetylcysteine. 6 It is postulated that the delayed effects produced by M&B 16,573 in the cat are due to the formation of 2,6-dimethoxyquinol and 2,6-dimethoxybenzoquinone in this species, the toxicity of the latter being reduced by sulphydryl compounds.

A simple gas chromatographic identification and determination of 11 CNS stimulants in biological samples. Application on a fatality involving phendimetrazine.

A method is presented for the simultaneous identification and quantification of several CNS stimulants, including amphetamine in plasma and urine by GC/FID using mephentermine as an internal standard. No derivation is necessary and after a single alkaline extraction, GC analysis for the 11 compounds tested is achieved in 23 min. The lower limit of detectability was found to be 4 ng/ml for amphetamine in plasma. This method is sensitive, reproducible, selective and applicable in forensic and clinical toxicological analyses. Toxicological findings, after a fatality involving phendimetrazine are presented as an application of the procedure.

Cases of overdosage with viloxazine hydrochloride (Vivalan).

Twelve cases of viloxazine overdosage are reported. All patients recovered without sequelae and no ECG abnormalities were observed. Gastric lavage was performed in most cases and was probably beneficial. As viloxazine is rapidly absorbed (Bayliss & Case 1975, Case & Reeves 1975) lavage should be carried out as soon as possible after the tablets are taken. Since the drug is almost exclusively excreted in the urine, it is suggested that forced diuresis be carried out to reduce blood levels as quickly as possible.

[Pathologico-morphologic picture of subchronic trimorfamide poisoning in dogs]. / Patologicko-morfologický obraz subchronickej intoxikácie psov trimorfamidom.

Animals in groups of six dogs and six bitches were given daily in their food, individually, for a period of six months, the fungicide trimorphamide, at dosages of 0, 300 and 500 mg.kg-1 of their weight. After they had been killed, a significant reduction in their weight was observed along with hemosiderosis of the liver, kidneys and spleen of all the experimental animals. No other important structural changes were found by dissection and pathologico-histological examinations of almost all organs and tissues.

[Acute poisoning by viloxazine chlorhydrate taken by itself]. / Intoxications aiguës par le chlorhydrate de viloxazine pris isolément.

One of the missions of the Poison Control Centres is to collect an important number of cases concerning a substance in order to determine its toxicological pattern for man. Such data were collected for Viloxazine chlorhydrate, an antidepressant belonging to a new chemical, ingested without association with other drugs, at doses varying from 100 mg to 4 g. The toxicological action of this drug was moderate, as no death occurred in the cases under study. The depression of the central nervous system was characterised only by a transitory loss of consciousness with recovery within a few hours. Two cases of convulsive seizure and one of extrapyramidal syndrome were the only complications in these intoxications. This confirms the difference between viloxazine and other antidepressants (tricyclics or IMAO inhibitors) whose toxic action on C.N.S. is more pronounced and sometimes complicated by cardiovascular disorders.

[Acute poisoning with L-triiodothyroinine, L-thyroxine and phendimetrazine bitartrate with suicidal intention]. / Akute Intoxikation mit L-Trijodthyronin, L-Thyroxin und Phendimetrazinbitartrat aus suizidaler Absicht

It is reported on an acute intoxication after application of 8 mg L-thyroxin, 2 mg L-triiodotyronine (200 tablets Thyreotom) and 4.5 g hendimetrazine bitartrate (100 tablets Sedafamem). The clinical picture is described. An endangering of the vital function of the organism was not observed. The symptoms disappeared after 4 days. The pharmacological aspects of the intoxication after application of the hormone of the thyroid gland, its significance for the pathogenesis of the thyreotoxic crisis and its therapy are discussed

Oxaflozane overdose in a child.

A case of severe poisoning in a 2 year-old child who ingested 150 mg of oxaflozane, a non-tricyclic antidepressant, is reported. After loss of consciousness, opisthotonos and coma, recovery was obtained with conservative treatment. Atropine-like symptoms were noted. The maximal plasma concentration of oxaflozane was 63 ng/mL. The elimination half-life for N-dealkyloxaflozane was 4.8 h.

Fatality from illicit phendimetrazine use.

Phendimetrazine is an anorectic agent which recently has been detected in three medical examiner's cases. In one instance death was attributed to this drug. Methods of detecting and identifying this drug in urine and blood are discussed. In the one instance where death was attributed to this substance, the blood concentration was 300 ng/ml.

[On the pathogenesis of the glomerulosclerosis ultrastructural and autoradiographic investigations on the rat kidney (author's transl)]. / Zur Pathogenese der Glomerulosklerose Ultrastrukturelle und autoradiographische Untersuchungen an der Rattenniere

The light- and electron microscopic changes in the glomeruli of the rat's kidney have been investigated in the course of ageing and after subtotal nephrectomy, constriction of the renal vein, and intoxication by N-nitrosomorpholine. In spite of the fact that four different experimental models have been used, identical changes were always found in the glomeruli. Morphologically they consisted of a diffuse thickening of the glomerular basement membrane and of an increase in the mesangial matrix without a proliferation of the glomerular cells. Despite this thickening of the glomerular basement membrane, functionally an increased permeability of the glomerular capillaries for macroproteins could be observed, shown by a moderate proteinuria. For these morphological changes the term "glomerulosclerosis" is suggested; they are interpreted as a non-specific, non-inflammatory reaction of the glomerulus to an impairment caused by a number of varied influences. From the study of the formal pathogenesis of the glomerulosclerosis presented here one can conclude that in the individual experimental models the same result has been achieved in different ways. One possibility in the development of glomerulosclerosis is an increased production of the components of the basement membrane and of the mesangial matrix. This is the pathway which appears to be followed after nephrectomy. Another possibility is a slowing down of the breakdown of both the matrix and the membrane. This seems to be the case in the glomerulosclerosis occuring in the course of ageing, and after hypoxic and toxic changes. It could be accounted for by a functional disturbance of, presumably, the mesangial cells responsible for the breakdown of the basement membrane and of the matrix. On the other hand, one may have to consider a primary alteration of the macromolecules of these structures, as is already known from studies of the, chemically closely related, collagen. The light- and electron microscopic studies of the normal and of the altered glomeruli have led to certain conclusions concerning the origin and the fomation of the glomerular basement membrane and the mesangial matrix. In order to widen the scope of the studies, additional autoradiographic investigations with 3H-proline and 3H-leucine have been performed in ultrathin and semithin sections of the rat's glomeruli. The results of the studies presented here suggest that of the three cell types of the glomerulus the visceral epithelial cells (podocytes, "Deckzellen") may participate on the formation of the glomerular basement membrane, whereas the mesangial cells appear to be responsible for the synthesis of the mesangial matrix.