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Drug interactions: a challenge in interpreting postmortem toxicology results and a problem in the clinical practice
Linköpings universitet, Institutionen för medicin och hälsa, Rättskemi. Linköpings universitet, Hälsouniversitetet.
Department of Forensic Medicine, Karolinska Institutet, Stockholm, Sweden.
Linköpings universitet, Institutionen för medicin och hälsa, Rättskemi. Linköpings universitet, Hälsouniversitetet.
(Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
Abstract [en]

Objective: Multiple drug intake is a problem in tbe clinical setting with potential to adverse drug reactions and certainly a problem in interpretation of forensic toxicology results. The aims of this investigation were to study the incidence of concomitant drugs in autopsy cases where citalopram or zopiclone were detected in femoral blood and to evaluate the potential of drug interactions.

Methods: All medico-legal autopsy cases in Sweden during 1992 to 2003 where citalopram or zopiclone were detected in femoral blood at the toxicological analyses were selected. The number and occurrences of concomitant drugs were recorded together with the concentrations as well as the cause of death.

Results: In the 2405 cases with citalopram, 123 different drugs, metabolites excluded, were detected 4679 times giving an average of 1.9 concomitant drugs and 1099 different dmg combinations were identified. The corresponding figures for the cases with zopiclone were 1557 cases, 118 different drugs detected 3984 times giving an average of 2.6 concomitant drugs and 977 different combinations. We found a strong positive correlation between the number of drugs detected and the frequency of cases judged to be intoxication.

Conclusions: Pharmacokinetic and pharmacodynamic interactions are a potential problem when interpreting forensic toxicological results and the conclusions about the cause and manner of death in the single case must be based on all available information from the investigation and tbe autopsy and on tbe knowledge of tbe pharmacology of included drugs. A better control of prescriptions of what different drugs an individual is given together with a comprehensive therapy control may reduce the risks of adverse drug reactions and unintended or accidental intoxications.

Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
URN: urn:nbn:se:liu:diva-85074OAI: oai:DiVA.org:liu-85074DiVA, id: diva2:564140
Tillgänglig från: 2012-11-01 Skapad: 2012-11-01 Senast uppdaterad: 2012-11-01
Ingår i avhandling
1. Postmortem toxicology: aspects on interpretation
Öppna denna publikation i ny flik eller fönster >>Postmortem toxicology: aspects on interpretation
2004 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Postmortem toxicology is a matter of analytical chemistry and the consequent interpretation of the results. Thus, both parts are of great importance to come to the right conclusion or the most probable explanation of the analytical results. When interpreting toxicological results there are a lot of different aspects to consider, such as: were the analytical methods used appropriate and with acceptable accuracy, what specimen was analyzed and how was it collected and stored before the analysis, what concentration of a drug can be considered normal or "therapeutic" and which concentration is fatal. Other circumstance to consider is the stability of the drug substances, the pharmacokinetics and pharmacodynamics of the drugs, possible drug interactions, pharmacogenetics and postmortem redistribution.

One crucial question in interpretation of postmortem toxicology results is to find reliable data on the significance of different drug concentrations. Instead of comparing concentrations found in postmortem blood with so called therapeutic concentrations in serum or plasma from the clinical setting, an inappropriate way that will lead to erroneous results, a new approach was used. Data was collected on drug concentrations in femoral blood from autopsy cases where the cause of death by certain not was intoxication and where the diseased was not incapacitated. These concentrations does not reflect any "therapeutic" concentration, which seldom is the key issue in postmortem toxicology, but represents concentrations which could be regarded as normally found and not associated with a fatal outcome. Applying this way to get reference concentrations, errors can be reduced and the problem associated with drug redistribution can be diminished.

Normally samples are stored for one year or more and for a variety of drugs no concentration changes in femoral blood were noted when stored at -20° C with the exception of e.g. ethanol, tetrahydrocannabinol (THC) and zopiclone. Vitreous humor (VH) can be used as an alternative specimen to blood and there exists a correlation between the concentration in VH compared to the blood concentration and the degree of protein binding of the substances. VH can also be used to estimate the corresponding blood concentration under certain circumstances.

Several drugs exist as racemate, containing two or several enantiomers. Chiral analysis can provide additional information about the time that has passed between intake of a drug and the time of death, thus improving the possibilities to predict whether an acute or chronic intake is at hand.

Pharmacokinetic and pharmacodynamic interactions are issues of great importance and have a great impact on interpretation in postmortem toxicology. Pharmacogenetics is another issue that attracts more and more attention in forensic toxicology. Awareness and knowledge of these factors are of utmost importance in order to produce accurate interpretations of postmortem toxicology results.

Ort, förlag, år, upplaga, sidor
Linköping: Linköping Universitet, 2004. s. 61
Serie
Linköping University Medical Dissertations, ISSN 0345-0082 ; 862
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:liu:diva-24323 (URN)3946 (Lokalt ID)91-7373-834-4 (ISBN)3946 (Arkivnummer)3946 (OAI)
Disputation
2004-10-15, Berzeliussalen, Hälsouniversitetet, Linköping, 13:00 (Svenska)
Opponent
Tillgänglig från: 2009-10-07 Skapad: 2009-10-07 Senast uppdaterad: 2012-11-01Bibliografiskt granskad

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Holmgren, PerAhlner, Johan

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