Glasgow Caledonian University1
Introduction
As the world wide population increases more demand is put on resources such as waste water treatment and drinking water supply. In our modern times most people will take medicines at some point in their lives and most of these medicines find their way into the waste water system by excretion. With changing disease profile, more people being treated at home and new medicines coming on to the market, the profile of pharmaceuticals present in waste water may slowly but continually shift. It is therefore important to review pharmaceutical use, to ensure there is an up to date profile of which drugs are cause for concern both now and in the future. The aim of this work is to review the drug prescribing pattern over a number of years, for drugs which are already of environmental concern and also drugs which may become harmful to the environment due to a changing or increasing pattern in prescribing. This will inform which substances require further investigation in the environment.
Methods
Using community prescription drug data in Scotland (2009-2014), (Information Services Scotland, 2010), initially the top 10 prescribed drugs were identified. This data showed that omeprazole has overtaken aspirin as the most prescribed drug. However the dose for each drug can vary therefore load (kg/annum) was calculated. A short-list of drugs was selected for further consideration. Metabolic pathways, breakdown mechanisms and excretion rates were also taken into consideration to determine whether metabolites and breakdown products should also be investigated in the environment.
Results/Discussion
Carbamazepine consistently has the highest load whereas simvastatin and omeprazole showed a sharp increase between 2001-2013. Carbamazepine is known to be persistent in the environment with very little removal during waste water treatment (Cunningham, V.L. et al., 2010). In a previous study, carbamazepine was found in 90% of community waste water samples tested over a 2 year period (PILLS Report, 2012). Carbamazepine metabolites may also be active and require investigation.
Omeprazole is regarded as a pro-drug and less than 0.1% is excreted unchanged in urine. There are two main metabolites excreted in human urine, hydroxy-omeprazole accounting for 15% of the dose and omeprazole acid accounting for 10% of the dose (Renberg et al., 1989). No data on the biological activity of these metabolites is available.
Atenolol was downgraded by the National Institute for Health Care Excellence (NICE) in 2006 as it was identified as provoking type 2 diabetes (Ladva, 2006). However, the prescription load has remained between 3000-4000 kg/annum since 2008. It is not metabolised and is degraded in waste water treatment to atenolol acid.
Simvastatin is one of the most prescribed drugs in Scotland and its load has increased dramatically from 441 kg in 2001 to 5001 kg in 2013, although the rate of increase has slowed since 2009. Simvastatin is a pro-drug with a complex metabolism and may be unstable in sewage conditions.
Lidocaine was considered as there has been a sharp increase in the prescribing of creams, patches and gels since 2007. An accurate load for lidocaine could not be calculated because of the formulation by which they are dispensed. Only 5% of the lidocaine dose is absorbed through the skin, the remainder will be washed off, potentially leading to an increase in environmental concentrations.
Donepezil is used in the treatment of Alzheimer's disease and donepezil load has increased from 1.85 kg in 2001 to 35.41 kg in 2014. With an increasing ageing population and a drive to keep patients at home for as long as possible, the rising trend in prescriptions is likely to continue. Although the load is relatively small, little is known about the environmental effects of donepezil and further investigation into the toxicity of donepezil to aquatic life is required.
Conclusion
An in-depth study of the prescribing patterns and pharmaceutical load has highlighted a big increase in simvastatin and omeprazole use since 2001. Although the load for donepezil is low the drug may be very potent and have environmental effects even at these low concentrations, more information about the toxicity of donepezil to aquatic life is required. The lidocaine data highlights the importance of knowing the formulation and drug metabolism as well as load and number of prescriptions.
Future work will include quantitation of the listed drugs and their metabolites in waste water. Two community waste water treatment plants in central Scotland have been identified for investigation. Samples of influent and effluent along with river water downstream of the discharge from these plants will be analysed using LCM/MS. This investigation will provide data on the effectiveness of waste water treatment in removal of the listed drugs. The degradation of simvastatin and omeprazole will also be examined in greater detail. 1. Cunningham, V.L. et al., (2010). Human health risk assessment of carbamazepine in surface waters of North America and Europe. Regulatory toxicology and pharmacology , Vol. 56(3), pp.343--351.
2. Information Services Scotland, (2010). Health-Topics/Prescribing-and-Medicines/Scottish-Drug-Tariff. Available at: http://www.isdscotland.org/Health-Topics/Prescribing-and-Medicines/Scottish-Drug-Tariff/.
3. Pharmaceutical Input and Elimination from Local Sources; Final report of the European cooperation project PILLS. 2012.
4. Renberg, L., et al., (1989). Identification of two main urinary metabolites of omeprazole in humans. Drug Metabolism and Disposition, Vol. 17, p.1.