OvertheCounter Monocyclic NonSteroidal AntiInf

Authors: Ariel Marchlewicz Urszula Guzik Danuta Wojcieszyńska

Publish Date: 2015/09/30

Volume: 226, Issue: 10, Pages: 355-

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Abstract

Recently the increased use of monocyclic nonsteroidal antiinflammatory drugs has resulted in their presence in the environment This may have potential negative effects on living organisms The biotransformation mechanisms of monocyclic nonsteroidal antiinflammatory drugs in the human body and in other mammals occur by hydroxylation and conjugation with glycine or glucuronic acid Biotransformation/biodegradation of monocyclic nonsteroidal antiinflammatory drugs in the environment may be caused by fungal or bacterial microorganisms Salicylic acid derivatives are degraded by catechol or gentisate as intermediates which are cleaved by dioxygenases The key intermediate of the paracetamol degradation pathways is hydroquinone Sometimes after hydrolysis of this drug 4aminophenol is formed which is a deadend metabolite Ibuprofen is metabolized by hydroxylation or activation with CoA resulting in the formation of isobutylocatechol The aim of this work is to attempt to summarize the knowledge about environmental risk connected with the presence of overthecounter antiinflammatory drugs their sources and the biotransformation and/or biodegradation pathways of these drugsIn an age of high level care of human health many pharmaceuticals are commonly used to cure or prevent diseases and other ailments such as headache muscle pain or inflammatory conditions Presently overthecounter drugs are very popular especially overthecounter monocyclic and polycyclic nonsteroidal antiinflammatory drugs NSAIDs Among these drugs the most popular and the most often used are monocyclic NSAIDs such as ibuprofen acetaminophen and salicylic acid and its derivatives like mesalazine due to their availability Ziylan and Ince 2011 For example the yearly intake of ibuprofen is up to 300 t in Germany 162 t in England and 58 t in Poland Sosnowska et al 2009 Guzik et al 2013a In the USA during 2001–2005 about 29 billion doses of paracetamol in all forms were sold Li et al 2014 The high intake of these widely available drugs may lead to their or their metabolites’ presence in the environment In connection with the presence of NSAIDs in the environment there is a risk of longterm exposure causing chronic toxic effect in organisms living there This may cause negative effects for living creatures and the accumulation of drugs or their metabolites in the food chain Carlsson et al 2006 Sosnowska et al 2009 Current knowledge about the microbial metabolism of nonsteroidal antiinflammatory drugs is still very little and the fact that we can find them in the environment suggests that sewage treatment plants are not currently adapted to completely remove these drugs before they reach the environment These drugs and their metabolites are found in wastewater influent and effluent from wastewater treatment plants For example in Germany acetylsalicylic acid was detected in the sewage effluents at 022 μg/L Heberer 2002 and paracetamol was detected in groundwater used as a source of public drinking water in California at 189 μg/L Li et al 2014 Observed metabolites are formed as a result of the metabolism by activated sludge microorganisms or enter the treatment plants as the human body biotransformation products with municipal wastewater Buser et al 1999 Zwiener et al 2002 MarcoUrrea et al 2009 Ziylan and Ince 2011 The fate of medicines including monocyclic NSAIDs in the natural environmental is still less known The main aim of this work is a compilation of the actual knowledge about sources and risks connected with the presence of monocyclic nonsteroidal antiinflammatory drugs in the environment Moreover authors describe microbiological degradation of the three most widespread painkillers antipyretic and antiinflammatory and overthecounter drugs—acetylsalicylic acid paracetamol and ibuprofenThe development of modern analytical methods makes it possible to detect NSAIDs in the environment Considering the high intake of drugs it may be assumed that this has an impact on the presence of pharmaceuticals in wastewaters and surface waters The main sources of drugs that reach the environment are excreted in nonmetabolized form or slightly modified ie hydroxylated conjugated and disposed of through the toilet Buser et al 1999 Heberer 2002 Khan and Ongerth 2002 Zwiener et al 2002 Metcalfe et al 2004 Nearly half of respondents declared the disposal of medications in the household trash That is why the presence of pharmaceuticals is expected in the landfill leachate or leachatecontaminated groundwater Kuspis and Krenzelok 1996 Musson and Townsend 2009 Hospitals’ wastewaters and discharges from pharmaceutical production also constitute a significant source of pharmaceuticals in the environment In many countries hospitals and pharmaceutical factories do not have separate wastewater treatment plants WWTP therefore these contaminants pass into the general wastewater treatment system Metcalfe et al 2004 The burdened sewage flows into WWTPs but not all NSAIDs are removed in biological sewage treatment with activated sludge Drug detection in WWTP effluent confirmed inadequacy of wastewater treatment plants to completely removing these pollutants from sewage Ternes 1998 Buser et al 1999 Tixier et al 2003 Lee et al 2005 Gómez et al 2007 Salgado et al 2010 Consequently this leads to the detection of drugs even in surface waters such as lakes or rivers Winkler et al 2001 Dębska et al 2005 Roberts and Thomas 2006 Vieno et al 2006 Togola and Budzinski 2008 Pailler et al 2009 Additionally Kolpin et al 2004 observed an increased concentration of drugs in downstream above places of outflows from WWTP

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