| 1. |
- Jönsson, Anna K., et al.
(författare)
-
Increased Risk of Drug-Induced Hyponatremia during High Temperatures
- 2017
-
Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 14:7
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate the relationship between outdoor temperature in Sweden and the reporting of drug-induced hyponatremia to the Medical Products Agency (MPA). Methods: All individual adverse drug reactions (ADR) reported to MPA from 1 January 2010 to 31 October 2013 of suspected drug-induced hyponatremia and random controls were identified. Reports where the ADR had been assessed as having at least a possible relation to the suspected drug were included. Information on administered drugs, onset date, causality assessment, sodium levels, and the geographical origin of the reports was extracted. A case-crossover design was used to ascertain the association between heat exposure and drug-induced hyponatremia at the individual level, while linear regression was used to study its relationship to sodium concentration in blood. Temperature exposure data were obtained from the nearest observation station to the reported cases. Results: During the study period, 280 reports of hyponatremia were identified. More cases of drug-induced hyponatremia were reported in the warmer season, with a peak in June, while other ADRs showed an opposite annual pattern. The distributed lag non-linear model indicated an increasing odds ratio (OR) with increasing temperature in the warm season with a highest odds ratio, with delays of 1-5 days after heat exposure. A cumulative OR for a lag time of 1 to 3 days was estimated at 2.21 at an average daily temperature of 20 degrees C. The change in sodium per 1 degrees C increase in temperature was estimated to be -0.37 mmol/L (95% CI: -0.02, -0.72). Conclusions: Warm weather appears to increase the risk of drug-induced hyponatremia.
|
|
| 2. |
- Karlsson, Sofia A., et al.
(författare)
-
The impact of a changed legislation on reporting of adverse drug reactions in Sweden, with focus on nurses' reporting
- 2015
-
Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 71:5, s. 631-636
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: In March 2007, a legislative amendment was issued in Sweden compelling nurses to report all suspected adverse drug reactions (ADRs) to the national pharmacovigilance system. The aims of this study were to describe the status of ADR reporting, before and after the implementation of the legislative changes, and to describe the general characteristics of suspected ADRs reported by nurses. Methods: The Swedish pharmacovigilance system during the study period constituted six regional centres responsible for the handling of all spontaneous ADR reports within their region. In this study, we identified all individual ADR reports from 2005 and 2010, analysed in depth the ADR reports from two regional centres and collated information about the reporter and the nature of the reported ADR. Results: From the two regional centres, a total of 898 and 1074 reports were submitted in 2005 and 2010 respectively. Nurses submitted 31% (275 reports) of the reports in 2005 and 24% (260 reports) in 2010. Nurses' reporting of serious ADRs was 3% (seven reports) in 2005 and 7% (17 reports) in 2010 with reporting of unlabelled ADRs at 4% (11 reports) in 2005 and 17% (45 reports) in 2010. Most of the serious and/or unlabelled reactions were related to vaccine administration (14 reports in 2005 and 36 reports in 2010). Conclusions: The overall ADR reporting by nurses did not appear to increase after the change in reporting legislation. The proportion of serious and/or unlabelled ADRs reported by nurses did however appear to increase during the same period. Taken together, our data suggests that further pro-active measures should be considered in order to involve nurses in the reporting of suspected ADRs.
|
|
| 3. |
- Lövborg, Henrik, et al.
(författare)
-
A fatal outcome after unintentional overdosing of rivastigmine patches
- 2012
-
Ingår i: Current drug safety. - : Bentham Science Publishers Ltd.. - 2212-3911 .- 1574-8863. ; 7:1, s. 30-32
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Rivastigmine is an acetylcholine esterase inhibitor used in the treatment of dementia. Patches with rivastigmine for transdermal delivery have been used to increase compliance and to reduce side effects.CASE REPORT: We describe an 87-year old male with dementia treated with multiple rivastigmine patches (Exelon 9,5 mg/24 h) who developed nausea, vomiting and renal failure with disturbed electrolytes resulting in death. The symptoms occurred after six rivastigmine patches had concomitantly been erroneously applied by health care personnel on two consecutive days. The terminal cause of death was considered to be uremia from an acute tubular necrosis that was assessed as a result of dehydration through vomiting. The rivastigmine intoxication was assessed as having caused or contributed to the dehydrated condition. The medication error occurred at least partly due to ambiguous labeling. The clinical signs were not initially recognized as adverse effects of rivastigmine.DISCUSSION: The presented case is a description of a rivastigmine overdose due to a medication error involving patches. This case indicates the importance of clear and unambiguous instructions to avoid administration errors with patches and to be vigilant to adverse drug reactions for early detection and correction of drug administration errors. In particular, instructions clearly indicating that only one patch should be applied at a time are important.
|
|
| 4. |
- Lövborg, Henrik, et al.
(författare)
-
A prospective analysis of the preventability of adverse drug reactions reported in Sweden
- 2012
-
Ingår i: European Journal of Clinical Pharmacology. - : Springer Verlag (Germany). - 0031-6970 .- 1432-1041. ; 68:8, s. 1183-1189
-
Tidskriftsartikel (refereegranskat)abstract
- Adverse drug reactions (ADRs) are a major patient safety issue, and a substantial proportion of ADRs are, in fact, preventable. The aim of this study was to describe the proportion and pattern of preventable ADRs in spontaneously reported suspected ADRs and to study the feasibility of using data from an ADR reporting system for this purpose. less thanbrgreater than less thanbrgreater thanAll reports of ADRs, except those in which a vaccine was the suspected drug, submitted to the regional pharmacovigilance center of southeastern Sweden between 2008 and 2009 were analyzed. Causality between the suspected ADR and the medication was assessed using the World Health Organization (WHO) criteria, and preventability was assessed using Hallas criteria. less thanbrgreater than less thanbrgreater thanDuring the study period, 1,290 ADRs were received and 1,255 were classified as having at least a possible causality between a reaction and a drug. Of these, 172 (14%) ADRs were considered preventable, 35 (20%) were classified as definitely preventable, and 137 (80%) as possibly preventable. Of all preventable ADRs, 96 (56%) were related to prescribing, 35 (20%) to administration, and 41 (24%) to clinical and laboratory monitoring of treatment. Warfarin, oxycodone, and ioversol were the most common drugs with preventable ADRs. less thanbrgreater than less thanbrgreater thanThis study found that a substantial part of reported ADRs are preventable. Most of these are related to drug prescription, suggesting that interventions aiming to reduce preventable ADRs should focus on this process. Moreover, systems for ADR reporting may be useful in the mission of reducing the unsafe use of drugs.
|
|
| 5. |
- Lövborg, Henrik, et al.
(författare)
-
Medication errors related to transdermal opioid patches: lessons from a regional incident reporting system
- 2014
-
Ingår i: BMC Pharmacology & Toxicology. - : BioMed Central. - 2050-6511. ; 15
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: A few cases of adverse reactions linked to erroneous use of transdermal opioid patches have been reported in the literature. The aim of this study was to describe and characterize medication errors (MEs) associated with use of transdermal fentanyl and buprenorphine. Methods: All events concerning transdermal opioid patches reported between 2004 and 2011 to a regional incident reporting system and assessed as MEs were scrutinized and characterized. MEs were defined as "a failure in the treatment process that leads to, or has the potential to lead to, harm to the patient". Results: In the study 151 MEs were identified. The three most common error types were wrong administration time 67 (44%), wrong dose 34 (23%), and omission of dose 20 (13%). Of all MEs, 118 (78%) occurred in the administration stage of the medication process. Harm was reported in 26 (17%) of the included cases, of which 2 (1%) were regarded as serious harm (nausea/vomiting and respiratory depression). Pain was the most common adverse reaction reported. Conclusions: Of the reported MEs related to transdermal fentanyl and buprenorphine, most occurred during administration. Improved routines to ascertain correct and timely administration and educational interventions to reduce MEs for these drugs are warranted.
|
|
| 6. |
- Lövborg, Henrik, et al.
(författare)
-
Structure-activity relationship analysis of cytotoxic cyanoguanidines : selection of CHS 828 as candidate drug.
- 2009
-
Ingår i: BMC research notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 2, s. 114-
-
Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: N-(6-(4-chlorophenoxy)hexyl)-N'-cyano-N''-4-pyridyl guanidine) (CHS 828) is the first candidate drug from a novel group of anti-tumour agents - the pyridyl cyanoguanidines, shown to be potent compounds interfering with cellular metabolism (inhibition of nicotinamide phosphoribosyl transferase) and NF-kappaB signalling. Substituted cyanoguanidines are also found in anti-hypertensive agents such as the potassium channel opener pinacidil (N-cyano-N'-(4-pyridyl)-N''-(1,2,2-trimethylpropyl)guanidine) and histamine-II receptor antagonists (e.g. cimetidine, N-cyano-N'-methyl-N''-[2-[[(5-methylimidazol-4-yl]methyl]thio]ethyl)guanidine). In animal studies, CHS 828 has shown very promising activity, and phase I and II studies resulted in further development of a with a water soluble prodrug. FINDINGS: To study the structural requirements for cyanoguanidine cytotoxicity a set of 19 analogues were synthesized. The cytotoxic effects were then studied in ten cell lines selected for different origins and mechanisms of resistance, using the fluorometric microculture cytotoxicity assay (FMCA). The compounds showed varying cytotoxic activity even though the dose-response curves for some analogues were very shallow. Pinacidil and cimetidine were found to be non-toxic in all ten cell lines. Starting with cyanoguanidine as the crucial core it was shown that 4-pyridyl substitution was more efficient than was 3-pyridyl substitution. The 4-pyridyl cyanoguanidine moiety should be linked by an alkyl chain, optimally a hexyl, heptyl or octyl chain, to a bulky end group. The exact composition of this end group did not seem to be of crucial importance; when the end group was a mono-substituted phenyl ring it was shown that the preferred position was 4-substitution, followed by 3- and, finally, 2-substitution as the least active. Whether the substituent was a chloro, nitro or methoxy substituent seemed to be of minor importance. Finally, the activity patterns in the ten cell lines were compared. Substances with similar structures correlated well, whilst substances with large differences in molecular structure demonstrated lower correlation coefficients. CONCLUSION: According to this structure-activity relationship (SAR) study, CHS 828 meets the requirements for optimal cytotoxic activity for this class of compounds.
|
|
| 7. |
- Rickardson, Linda, et al.
(författare)
-
Image-based screening for the identification of novel proteasome inhibitors
- 2007
-
Ingår i: Journal of Biomolecular Screening. - : Elsevier BV. - 1087-0571 .- 1552-454X. ; 12:2, s. 203-210
-
Tidskriftsartikel (refereegranskat)abstract
- The proteasome is a new, interesting target in cancer drug therapy, and the proteasome inhibitor bortezomib has shown an effect in myeloma patients. It is of interest to efficiently discover and evaluate new proteasome inhibitors. The authors describe the development of an image-based screening assay for the identification of compounds with proteasome-inhibiting activity. The stably transfected human embryo kidney cell line HEK 293 ZsGreen Proteasome Sensor Cell Line expressing the ZsProSensor-1 fusion protein was used for screening and evaluation of proteasome inhibitors. Inhibition of the proteasome leads to accumulation of the green fluorescent protein ZsGreen, which is measured in the ArrayScan® High Content Screening system, in which cell morphology is studied simultaneously. When screening the LOPAC1280 substance library, several compounds with effect on the proteasome were found; among the hits were disulfiram and ammonium pyrrolidinedithiocarbamate (PDTC). Cytotoxic analysis of disulfiram and PDTC showed that the compounds induced cytotoxicity in the myeloma cell line RPMI 8226. The average Z' value for the assay was 0.66. The results indicate that the assay rapidly identifies new proteasome- inhibiting substances, and it will be further used as a tool for image-based screening of other chemically diverse compound libraries.
|
|
| 8. |
|
|
