Fatal toxicity index of medicinal drugs based on a comprehensive toxicology database

The fatal toxicity index (FTI) is the absolute number of fatal poisonings caused by a particular drug divided by its consumption figure. Consequently, it is a useful measure in evaluating toxicity of the drug and its relevance in fatal poisonings. In this study, we assessed the FTI of medicinal drugs in 3 years (2005, 2009, and 2013) in Finland. As the measure of drug consumption, we used the number of defined daily doses (DDD) per population in each year. There were 70 medicinal drugs in Finland for which the mean FTI expressed as the number of deaths per million DDD over the three study years was higher or equal to 0.1. The Anatomical Therapeutic Chemical (ATC) classification system was used for the classification of the active ingredients of medicinal drugs according to the organ or system which they act on. Of these 70 drugs, 55 drugs (78.6 %) acted on the nervous system (denoted by ATC code N), 11 (15.7 %) on the cardiovascular system (C), three (4.3 %) on the alimentary tract and metabolism (A), and one (1.4 %) on the musculoskeletal system (M). The nervous system drugs consisted of 20 psycholeptics, (ATC code N05), 20 psychoanaleptics (N06), eight analgesics (N02), six antiepileptics (N03), and one other nervous system drug (N07). The highest individual FTIs were associated with the opioids methadone, dextropropoxyphene, oxycodone, tramadol, and morphine; the antipsychotics levomepromazine and chlorprothixene; and the antidepressants doxepin, amitriptyline, trimipramine, and bupropion. Buprenorphine was not included in the study, because most of the fatal buprenorphine poisonings were due to smuggled tablets. A clearly increasing trend in FTI was observed with pregabalin and possibly with bupropion, both drugs emerging as abused substances.Peer reviewe

Purchases of prescription drugs before an alcohol-related death : A ten-year follow-up study using linked routine data

Background: Physician's intention to prescribe drugs could potentially be used to improve targeting of alcohol interventions and enhanced disease management to patients with a high risk of severe alcohol-related harm within outpatient settings. Methods: Comparison of ten-year incidence trajectories of 13.8 million reimbursed purchases of prescription drugs among 303,057 Finnish men and women of whom 7490 ultimately died due to alcohol-related causes (Ale+), 14,954 died without alcohol involvement (Alc-), and 280,613 survived until the end of 2007. Results: 5-10 years before death, 88% of the persons with an Alc+ death had received prescription medication, and over two-thirds (69%) had at least one reimbursed purchase of drugs for the alimentary tract and metabolism, the cardiovascular system, or the nervous system. Among persons with an Alc+ death, the incidence rate (IR) for purchases of hypnotics, and sedatives was L38 times higher (95% confidence interval (C1):1.32,1.44) compared to those with an Alc death, and 4.07 times higher (95%C1:3.92,4.22) compared to survivors; and the IR for purchases of anxiolytics was 1.40 times higher (95%Ck1.34,1.47) compared to those with an Ale death, and 3.61 times higher (95%C1:3.48,3.78) compared to survivors. Conclusions: Using physician's intention to prescribe drugs affecting the alimentary tract and metabolism, cardiovascular system and nervous system could potentially be used to flag patients who might benefit from screening, targeted interventions or enhanced disease management. In particular, patients who are to be prescribed anxiolytics, hypnotics, and sedatives, and antidepressants may benefit from enhanced interventions targeted to problem drinking.Peer reviewe

Unintentional drowning : Role of medicinal drugs and alcohol

Background: Alcohol is a well-known risk factor in unintentional drownings. Whereas psychotropic drugs, like alcohol, may cause psychomotor impairment and affect cognition, no detailed studies have focused on their association with drowning. Finland provides extensive post-mortem toxicological data for studies on drowning because of its high medico-legal autopsy rates. Methods: Drowning cases, 2000 through 2009, for which post-mortem toxicological analysis was performed, came from the database of the Toxicological Laboratory, Department of Forensic Medicine, University of Helsinki, using the ICD-10 nature-of-injury code T75.1. The data were narrowed to unintentional drowning, using the ICD-10 external-injury codes V90, V92, and W65-74. Each drowning case had its blood alcohol concentration (BAC) and concentrations of other drugs recorded. Evaluation of the contribution of psychotropic drugs to drowning was based on their blood concentration by means of a 6-grade scale. Results: Among victims >= 15 years old, unintentional drownings numbered 1697, of which, 303 (17.9%) were boating-related and 1394 (82.1%) non-boating-related. Among these, 65.0% of boating-related and 61.8% of non-boating-related victims were alcohol-positive (=BAC >= 50 mg/dL). The male-to-female ratio in alcohol-positive drownings was 7.3. At least one psychotropic drug appeared in 453 (26.7%) drowning cases, with some victims' bodies showing up to 7 different drugs. Overall 70 different psychotropic drugs were detectable, with 134 (7.9%) cases both alcohol-negative and psychotropic-drug-positive, of these, 59 (3.5%) were graded 4 to 6, indicating a possible to very probable contribution to drowning. Our findings suggest that psychotropic drugs may play a significant role in drowning, in up to 14.5% of cases, independently or in association with alcohol. Conclusions: Psychotropic drugs alone or in association with alcohol may be an overlooked risk factor in drowning, due to their effects on psychomotor function and cognition. Future studies should also address other mechanisms-for instance drug-induced long-QT syndrome-by which drugs may contribute to drowning.Peer reviewe

Suomalainen huumekuolema 2007 : Poikkitieteellinen tutkimus oikeuslääketieteellisistä kuolinsyyasiakirjoista

Nimekesivulla myös: Nuorisotutkimusverkost

Oikeuskemiallisesti todetut myrkytyskuolemat Suomessa vuonna 1981

Summary: Fatal Poisonings Verified in Forensic Chemistry Examinations in Finland in 1981

The alpha v beta 1 integrin functions as a fibronectin receptor but does not support fibronectin matrix assembly and cell migration on fibronectin

The fibronectin receptor, alpha 5 beta 1, has been shown to be required for fibronectin matrix assembly and plays an important role in cell migration on fibronectin. However, it is not clear whether other fibronectin binding integrins can take the place of alpha 5 beta 1 during matrix assembly and cell migration. To test this, we expressed the human alpha v subunit in the CHO cell line CHO-B2 that lacks the alpha 5 subunit. We found that the human alpha v combined with CHO cell beta 1 to form the integrin alpha v beta 1. Cells that expressed alpha v beta 1 attached to and spread well on fibronectin-coated dishes, but did so less well on vitronectin-coated dishes. This, along with other data, indicated that alpha v beta 1 functions as a fibronectin receptor in CHO-B2 cells. The alpha v beta 1-expressing cells failed to produce a fibronectin matrix or to migrate on fibronectin, although the same cells transfected with alpha 5 do produce a matrix and migrate on fibronectin. The affinity of the alpha v beta 1-expressing cells for fibronectin was fourfold lower than that of the alpha 5 beta 1- expressing cells. In addition, alpha v beta 1 was distributed diffusely throughout the cell surface, whereas alpha 5 beta 1 was localized to focal adhesions when cells were seeded onto fibronectin-coated surfaces. Thus, of the two fibronectin receptors, alpha v beta 1 and alpha 5 beta 1, only alpha 5 beta 1 supports fibronectin matrix assembly and promotes cell migration on fibronectin in the CHO-B2 cells. Possible reasons for this difference in the activities of alpha v beta 1 and alpha 5 beta 1 include the lower affinity of alpha v beta 1 for fibronectin and the failure of this integrin to localize in adhesion plaques on a fibronectin substrate. These results show that two integrins with similar ligand specificities and cell attachment functions may be quite different in their ability to support fibronectin matrix assembly and cell motility on fibronectin