The Life-Cycle of Pharmaceuticals in the Environment

B.M. Peake, R. Braund, Alfred Tong, Louis A Tremblay

• Publisher: Woodhead Publishing
• Year: 2015
• Print ISBN:
  9781907568251
• eBook ISBN:
  9781908818454
• Topic: Medicine
• Subtopic: Pharmacology

The Life-Cycle of Pharmaceuticals in the Environment identifies pathways of entry of pharmaceuticals into the environment, beginning with the role of global prescribing and disposal practices. The book then discusses typical levels of common pharmaceuticals and how they can be determined in natural waters such as raw and treated sewage, and in potable water. In addition, sections examine methods currently available to degrade pharmaceuticals in natural waters and some of their ecotoxicological impacts, along with future considerations and the growing concept of product stewardship. - Encompasses the full lifecycle of common pharmaceuticals, from prescription and dispensing practices to their occurrence in a range of different types of natural waters and their environmental impact - Explores the role of the healthcare system and its affect on users - Beneficial for environmental engineers involved in the design and operation of appropriate degradation technologies of the pharmaceutical prescription and disposal practices

1

Introduction

Abstract

Pharmaceuticals are gaining recognition as part of a larger group of emerging contaminants within the environment. The potential risk associated with these products both individually and collectively is still subject to debate; however, the increasing production and consumption of pharmaceuticals globally is worthy of further consideration and investigation as evidenced by the growing research being published in this area.

This chapter sets the scene for the increased interest in this growing area, identifies the pathways of entry into the environment, and provides the platform framework for the remainder of the text.

Keywords

Pharmaceuticals

Environmental risk

Emerging contaminants

1.1 Overview: Do pharmaceuticals pose a significant environmental risk?

The global community is becoming increasingly aware of both the environmental presence and the real or potential environmental impact of man-made chemicals (anthropogenic compounds) such as pesticides, personal care products, and pharmaceuticals. In the past, the large-scale chemical wastes associated with their industrial production were considered and known to pose significant environmental risks if their environmental discharge was not monitored. However, after appropriate measures were placed worldwide on controlling the production and disposal of industrial waste, it became apparent that new emerging contaminants comprising many anthropogenic compounds could also be potentially detrimental to the environment.

The first group of these emerging contaminants to receive notoriety were pesticides. In 1962, a book written by Rachel Carson entitled Silent Spring raised issues concerning public misinformation on the safety of pesticide use in the US, particularly dichlorodiphenyltrichloroethane (DDT) and its adverse effects on bird life. This was followed by the realization that many other chemicals were commonly present in consumer products (Halden, 2010). Perchlorinated and perfluorinated hydrocarbons used as flame retardants in clothing, carpets, and upholstery have the potential to persist and bioaccumulate in wildlife, and a major issue raised by the scientific community at that time was how best to manage these chemicals in redundant consumer goods placed in landfills (Weber et al., 2011). Public concerns about emerging contaminants escalated from the discovery that certain compounds disrupted the hormonal (endocrine) systems of a range of organisms and as such have the potential to detrimentally affect human and animal functions in trace quantities over a prolonged period of exposure. For example, detrimental effects on the reproductive health of humans have been associated with the use of bisphenol A as a plasticizer in water bottles, microwaveable containers, and other household products (Ohlson and Hardell, 2000).

Given the increased global production and use of these anthropogenic chemicals in modern-day society by governments, local bodies, corporations and private individuals and the myriad of new anthropogenic chemicals consistently available over time, it could be predicted that environmental pollution associated with these chemicals would become increasingly important in the twenty-first century (Kummerer, 2010). The recognition that private individuals and small communities can pollute the environment and lead to the release of contaminants at detectable levels was a significant milestone (Daughton, 2007). Such a concept was soon realized for pharmaceuticals and personal care products, which are often collectively referred to by the environmental science community as PPCPs.

Personal care products are a heterogeneous group of chemical substances that are used for various health, beauty, and hygiene formulations. Such chemicals may be present in everyday cosmetic items such as sunscreen lotions, lip balm, perfumes, shampoos, and toiletries as diverse as toothpaste, mouthwash, and shaving cream. On the other hand, pharmaceuticals (or drugs) are largely defined in various acts and regulations around the world (such as the Medicines Act 1981 and Medicines Regulations 1984 in New Zealand legislation) as chemical substances or medicines used therapeutically for humans or animals to treat illnesses or ailments. However, there are some regional variations on what constitutes a pharmaceutical or medicine. For example, animal remedies are not considered medicines under the above act and regulations in New Zealand legislation. Because of the broad definition of PPCPs, it was clear from the very onset that it is unlikely there will ever be a single approach to effectively minimize and control their discharge into the environment.

The production of pharmaceuticals is a significant economic activity for pharmaceutical industries around the world. A total of US$954 billion was spent on prescription medications globally in 2011 alone (see IMS Total Unaudited and Audited Global Pharmaceutical Market By Region, http://www.imshealth.com/deployedfiles/ims/Global/Content/Corporate/Press%20Room/Top-Line%20Market%20Data%20&%20Trends/2011%20Top-line%20 Market %20Data/Regional Pharma_Market_by_Spending_2011-2016.pdf, accessed 10-6-14). In addition, much money has been spent globally on the direct-to-consumer marketing of both therapeutic and lifestyle drugs. The increasing number of new drug entities and the various dosage forms available (i.e., tablets, creams, ointments, and suspensions) to satisfy the demands of modern healthcare have made pharmaceuticals more affordable to the consumer than ever before. In 2013 alone, over 100 new formulations or chemical entities were approved by the US Food and Drug Administration (FDA) for clinical use (http://www.centerwatch.com/drug-information/fda-approvals/, accessed 10-6-14).

Given the money that is spent by many governments and consumers in funding the insatiable need for pharmaceuticals in healthcare and the wide availability of therapeutic agents, the progression of a pharmaceutical from synthesis in the laboratory to market is also a costly business. Billions of dollars are typically spent by pharmaceutical companies to develop a new chemical compound with a vision that this potential drug will be a commercial success in the market (Yamane et al., 2013). Drug development typically involves three phases: a preclinical phase which seeks to gather the pharmacological behavior of the chemical generally in laboratory animals or isolated tissues, a clinical phase where the drug is tested in both healthy and sick volunteers in order to determine its effects on humans, and finally, a postmarketing surveillance phase where the new chemical entity (which is now considered a medicine) is used in the general population (Nutt and Attridge, 2014). Here, pharmacovigilance data related to the use of the new medicine are reported through everyday clinical use, and this aspect is especially important for the determination of any adverse effects which may not have been apparent or observed during the earlier stages of clinical testing (Yamane et al., 2013; Chen et al., 2014). If any excessive adverse drug reactions (ADRs) or major concerns over public safety are reported, the new medicine could be withdrawn from market, and there have been some notable historical examples of this happening.

In 1957, thalidomide was withdrawn as an over-the-counter medication for nausea and morning sickness due to the belated reports of the development of phocomelia (limb deformations in fetuses) in pregnancy (Diggle, 2001). A lawsuit against the pharmaceutical company that developed the drug (Grunenthal) ensued (Botting, 2002). In 1999, Merck and Co. (now Merck Sharpe and Dome, MSD) marketed the drug rofecoxib (Vioxx) as a specific nonsteroidal anti-inflammatory drug (NSAID) inhibitor of cyclooxygenase isoenzyme 2 (COX-2) (McIntyre and Evans, 2014). COX-2 is responsible for the production of inflammatory mediators in the human body, whereas cyclooxygenase isoenzyme 1 (COX-1) is a constitutive enzyme responsible for the maintenance of various physiological functions (Howard and Delafontaine, 2004). It was envisioned that the use of COX-2-specific inhibitors would be associated with a lower incidence of major gastrointestinal events, such as stomach ulcers and bleeding, compared to the use of nonspecific NSAIDs which also prevented mucus formation by COX-1, which has been known to occur with heavy aspirin use and hence have the potential to aggravate peptic ulcer formation (Katz, 2013). However, MSD withdrew the rofecoxib from the market in 2004 in the light of evidence that showed that its use was associated with an increased risk of myocardial infarction compared to nonspecific NSAIDs (Collins et al., 2013).

As can be seen from these instances of postmarketing withdrawals of new pharmaceuticals, drug development ventures are not only costly but also risky for a drug development company. For a new chemical entity to be a success, profits made from the marketing and sales of the drug must cover all of the earlier development costs (Bansal et al., 2009). Usually, a 10-year patent period is given to an innovator product (the first drug of a new chemical entity marketed) which prevents other pharmaceutical companies from producing generic products that can compete with the innovator product on the market and drastically reduce the revenue obtained by the pharmaceutical company for the development of the original product (Knezevic and Griffiths, 2011). Drug development and marketing is a high-stakes process. As we have seen, if the risks of using a drug outweigh the clinical benefits, government health departments around the world can decide to withdraw the drug from the market. This could potentially be the worst outcome for a pharmaceutical company which has invested billions of dollars on the development of a drug but cannot recuperate the costs of the development from any subsequent sales. In short, the public perception and reputation of the drug among authorities is everything to a drug development corporate. As we will discuss later, given that the risks for many of these pharmaceuticals cannot be accurately evaluated, inaccurate information about the environmental effects of pharmaceutical contaminants can generate a frenzied media phenomenon which may vilify a drug when it does not necessarily deserve such a reputation. In such a hypothetical situation where the drug is withdrawn on such a media-frenzied reputation, not only will a pharmaceutical company suffer financial loss but patients will also lose out on what could be an effective therapy. As we will discuss in Chapter 4, given that pharmaceuticals are typically detected in low concentrations in the environment and the lack of conclusive evidence in many instances that such levels are detrimental to flora and fauna (Chapter 5), will some drugs fall prey to postmarketing withdrawal in the future in the midst of unverified environmental activism and sensationalism? In Chapter 7, we look at some of the dilemmas faced by regulatory and legislative authorities associated with setting minimum guideline values to reflect the environmental concentration of particular pharmaceuticals considered to be persistent organic pollutants in the light of often limited information.

Investigations into the environmental impact, fate, and behavior of pharmaceuticals have only been undertaken in the last 40 years or so (Stumm-Zollinger and Fair, 1965). In the 1970–80s, the concept of natural and synthetic estrogens as contaminants in the environment was first considered and their behavior during sewage treatment studied (Tabak and Bunch, 1970; Tabak et al., 1981). The drive to learn more about contaminants in wastewater was made greater due to the concept of reuse of urban waste water beginning in the 1980s (Rice, 1999). While many cities around the world currently still do not reuse wastewater, there are some exceptions. For example, the cities of Windhoek in Namibia and Singapore are both dependent on water recycling to support their inhabitants due to the scarcity of natural sources of freshwater in these areas (Isaacson and S...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Dedication
• Foreword
• Acknowledgements
• 1: Introduction
• 2: Prescribing practices
• 3: Disposal of unused medications
• 4: Detection and presence of pharmaceuticals in the environment
• 5: Impact of pharmaceuticals on the environment
• 6: Degradation of pharmaceuticals in wastewater
• 7: Regulatory practices to control the discharge of pharmaceuticals into the environment
• 8: Green chemistry, green pharmacy, and life-cycle assessments
• 9: Summary and Conclusions
• Index