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EDITORIAL
Year : 2012  |  Volume : 44  |  Issue : 5  |  Page : 547-549
 

Ecopharmacovigilance: An issue urgently to be addressed


Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh, India

Date of Web Publication31-Aug-2012

Correspondence Address:
Bikash Medhi
Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0253-7613.100363

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How to cite this article:
Medhi B, Sewal RK. Ecopharmacovigilance: An issue urgently to be addressed. Indian J Pharmacol 2012;44:547-9

How to cite this URL:
Medhi B, Sewal RK. Ecopharmacovigilance: An issue urgently to be addressed. Indian J Pharmacol [serial online] 2012 [cited 2018 Oct 17];44:547-9. Available from: http://www.ijp-online.com/text.asp?2012/44/5/547/100363


"Every rose has its thorn" and so have the drugs too. Drugs have been a boon for the humanity in curbing the ailments though not fully but to a great extent. Along with beneficial effects they also impart some adverse reactions sooner or later. Owing to this fact, a new branch of science called "Pharmacovigilance" sprouted in 1960 after the incidence of thalidomide disaster. [1] Pharmacovigilance became well accepted and practiced in developed world but developing part of globe consumed decades to it. At present, India has also started a national program to monitor the adverse effects of drugs. [2] Unfortunately, however, despite this achievement worldwide, the effect of drug use on environment remains unaddressed. The exorbitant decline in number of vultures in Indian subcontinent shook the environmental scientists and activists. [3] Prior to this observation, research on the impact of chemical pollution was restricted to persistent organic pollutants. [4] At this verge, attention has been drawn to the environmental impact of chemicals used in small concentration, that is, drugs giving birth to the subject of ecopharmacovigilance. Ecopharmacovigilance can be defined as science and activities concerning detection, assessment, understanding, and prevention of adverse effects or other problems related to the presence of pharmaceuticals in the environment, which affect human and other animal species. [5]


  Sources of Entry of Pharmaceuticals into Environment Top


Drug use in both the human and veterinary population is escalating day by day. According to one estimate 100,000 tons of antimicrobials are consumed every year. [6] More than 30 billion doses of nonsteroidal antiinflammatory drugs (NSAIDs) are consumed annually in the United States only. [7] Consumed drug passes out of the system either as metabolites or unchanged through excretion. Drugs are usually water soluble and therefore find their way into the sewage. Industrial waste of the pharmaceutical companies also contributes toward the entry of drugs into the environment. Though such industries adopt the sewage treatment process before disposal but because of their obsolete processes the contamination of environment by

drugs continues. Few drugs are not entirely removed by treatment process leaving their traces to go into water in environment. [8] Cocaine, oral contraceptives, carbamazepine, and iodine contrast media are some of the examples. [9-11] Cocaine has been detected in Po river in Italy. [12] In Niagara river antidepressant drugs, carbamazepine and other antileptics, and lipid-regulating agents (statins) were detected. [13] Apart from these, there are numerous examples of drugs found in aquatic environment. These include antibacterials like flouroquinolones, hormones, paracetamol, diclofenac, etc. Thus water becomes contaminated although with minimum amount of numerous drugs. Supplied as drinking water, it leads to an unwitting re-entry of drugs into humans.

Such pollution of environment by the drugs or their metabolites is creating an alarming situation. According to a report published in Washington Times, treated waste water taken from a plant in an industrial area in south India where about 90 Indian drug factories dump their residues, it was revealed that enough of a single, powerful antibiotic was being spewed into one stream each day to treat every person in a city of 90,000. Waste water downstream from the Indian plants contained 150 times the highest levels detected in the United States of America. [14]Sewage contaminated with traces of drugs may also be used in irrigation. Drugs or their metabolites also find their path to enter the food chain through this route.

Leftover medicines constitute another dominating cause of environmental contamination with drugs. Improper disposal of leftover medication usually contaminates the environment to a great extent. Drug residuals from the formulations like transdermal patches also leave the significant amount of drug in environment. [15] Transdermal patches containing fentanyl are reported to retain 28-84% of the loaded drug after removal from skin. [16]


  Consequences of Environmental Pollution by Pharmaceuticals Top


Exposure of human beings and animals to drugs through environment affects them directly or indirectly. The foremost in discussion is microbial resistance. Continuous exposure to low dose of antimicrobials through drinking water may bring resistance. Decreasing interest of pharmaceutical companies in development of new antimicrobials in favor of developing "lifestyle" drugs may add on to the problem.[17] Although, effect of very low doses from the environmental cycling is not clear, special populations like pregnant women, children, geriatric population, persons with renal or hepatic insufficiencies may remain at a greater risk to such exposure because in these categories the pharmacokinetics gets altered and even minor doses may also prove to be toxic. [18] Similarly, some drugs in these micro doses may also show synergistic actions. Nocebo effect of the drugs even in subtherapeutic concentrations present in environment cannot be ruled out. Moreover, type B adverse reactions may also take place at these doses. [11]

Some examples of impact of drugs through environment on human beings and animals are cited here. The foremost is a substantial decline in number of vultures in Indian subcontinent secondary to their indirect exposure to diclofenac. A study from Pakistan revealed that due to the use of diclofenac in treatment of livestock and consumption of their dead bodies by vultures led to the kidney failures of these vultures. [19] Consequently over a period of time population of vultures declined so drastically that they were declared endangered species. Various Government and nonGovernmental organizations became active to save these most efficient scavengers of nature. Similarly,

Government of India also banned diclofenac in India for veterinary use. [20] Sterility in frogs due to traces of oral contraceptive pills in water became the cause of decrease in number of frogs. [21]Ivermectin which is used as anthelmintic in veterinary practice gets excreted through feces and subsequently affects other organisms like dung beetle adversely. [22] Presence of sex hormone in aquatic environment has also feminized the male fishes. Few workers have also tried to correlate the alarming decline in sperm count in men that has decreased by 50% in 50 years.[23] Several persons get unintentionally exposed to an array of drugs through environment. Not only the drugs but also the excipients used in the formulations may pose a threat to the environment.[24]


  Remedial Measures Top


Drug use has become an inevitable part of our lives but it is not imperative to compromise with the balance of ecosystem on any grounds. Solutions need to be suggested to save this only livable planet from ill effects of these chemicals. These may include better sewage treatment plants, education over rational use of drugs, and development of biodegradable products. [25]Biopharmaceuticals may be an alternative but we still lack a scientific evidence to accept them as a complete substitute of drugs in practice. [26]

A mandatory provision may be made in the process of drug development to establish safety in the context of environment and a study of the impact of drug over environment. Environmental Risk Assessment (ERA) has become mandatory before seeking market authorization of drugs in European Union (EU). We should, however, remember that the results of ERA are affected by several factors like dose of the drug used, characteristics of drug, metabolism of drug, biodegradation, measured environmental concentration, and ecotoxicity. It is also difficult to predict the chronic hazard potential of a drug in subacute concentrations on the basis of acute toxicity studies. [27],[28] Countries like United Kingdom have witnessed the impact of stringent regulations. The American Senate has also passed a legislation to monitor the drugs in environment. As stated above, a number of Governmental and nonGovernmental organizations have also taken initiatives. Few of them are proving to be benchmark for international stakeholders, for example, in Nepal aviaries are being constructed following their success in Pinjore, India. But India with a multifold (almost 150 times) contamination as compared with developed countries is still striving for a robust system to safeguard the environment. Attention is paid to the culprit drugs only after the alarming episodes are reported. It will now be pertinent for regulatory as well as scientific society to work hand in hand to address this vital issue.

 
  References Top

1.Grootheest KV. The dawn of Pharmacovigilance: An historical prospective. Int J Pharm Med 2003;17:195-200.  Back to cited text no. 1
    
2.Gupta YK. Ensuring Patient Safety - Launching the New Pharmacovigilance Programme of India. Pharma Times 2010;42:21-6.  Back to cited text no. 2
    
3.Prakash V, Green RE, Pain DJ, Ranade SP, Saravanan S, Prakash N, et al. Recent changes in populations of resident Gyps vultures in India. J Bombay Nat Hist Soc 2007;104:129-35.  Back to cited text no. 3
    
4.Jones OA, Lester JN, Voulvoulis N. Pharmaceuticals: A threat to drinking water? Trends Biotechnol 2005;23:163-7.  Back to cited text no. 4
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5.Silva LJG, Lino CM, Meisel L, Barceló D, Pena A. Ecopharmacovigilance. In: Barcelo D, The Handbook of Environmental Chemistry, Germany: Springer-Verlag Berlin and Heidelberg GmbH & Co. KG; 2012. p. 213-42.  Back to cited text no. 5
    
6.Wise R. Antimicrobial resistance: Priorities of action. J Antimicrob Chemother 2002;49:585-6.  Back to cited text no. 6
    
7.Green G. Understanding NSAIDs: from aspirin to COX-2. Clin Cornerstone 2001;3:50-60.  Back to cited text no. 7
    
8.Joss A, Zabczynski S, Gobel A, Hoffmann B, Loffler D, McArdell CS, et al. Biological degradation of pharmaceuticals in municipal wastewater treatment: Proposing a classification scheme. Water Res 2006;40:1686-96.  Back to cited text no. 8
    
9.Zuccato E, Chiabrando C, Castiglioni S, Calamari D, Bagnati R, Schiarea S, et al. Cocaine in surface waters: A new evidence-based tool to monitor community drug abuse. Environ Health 2005;4:14.   Back to cited text no. 9
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10.Kolpin DW, Furlong ET, Meyer MT, Thurman EM, Zaugg SD, Barber LB, et al. Pharmaceuticals, hormones, and other organic wastewater contaminants in U.S. streams, 1999-2000: A national reconnaissance. Environ Sci Technol 2002;36:1202-11.  Back to cited text no. 10
    
11.Velo G, Moretti U. Ecopharmacovigilance for better health. Drug Saf 2010;33:963-8.  Back to cited text no. 11
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12.Castiglioni S, Fanelli R, Calamari D, Bagnati R, Zuccato E. Methodological approaches for studying pharmaceuticals in the environment by comparing predicted and measured concentrations in River Po, Italy. Regul Toxicol Pharmacol 2004;39:25-32.  Back to cited text no. 12
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13.Heberer T. Occurrence, fate, and removal of pharmaceuticals residues in the aquatic environment: A review of recent research data. Toxicol Lett 2002;131:5-17.  Back to cited text no. 13
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14.World's highest drug levels entering India stream. The Washington Times, 2009 Jan 26.  Back to cited text no. 14
    
15.Daughton CG, Ruhoy IS. The afterlife of drugs and the role of pharmEcovigilance. Drug Saf 2008;31:1069-82.  Back to cited text no. 15
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16.Marquardt KA, Tharratt RS, Musallam NA. Fentanyl remaining in a transdermal system following three days of continuous use. Ann Pharmacother 1995;29: 969-71.  Back to cited text no. 16
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17.Charles PG, Grayson ML. The dearth of new antibiotic development: Why we should be worried and what we can do about it. Med J Aust 2004;181: 549-53.  Back to cited text no. 17
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18.Lai KM, Scrimshaw MD, Lester JN. The effects of natural and synthetic steroid estrogens in relation to their environmental occurrence. Crit Rev Toxicol 2002;32:113-32.  Back to cited text no. 18
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19.Oaks JL, Gilbert M, Virani MZ, Watson RT, Meteyer CU, Rideout BA, et al. Diclofenac residues as the cause of vulture population decline in Pakistan. Nature 2004;427:630-3.  Back to cited text no. 19
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20.Taggart MA, Senacha KR, Green RE, Jhala YV, Rahmani AR. Diclofenac residues in carcasses of domestic ungulates available to vultures in India. Environ Int 2007;33:759-65.  Back to cited text no. 20
    
21.Kvarnryda M, Grabicb R, Brandta I, Berg C. Early life progestin exposure causes arrested oocyte development, oviductal agenesis and sterility in adult Xenopus tropicalis frogs. Aquat Toxicol 2011;103:18-24.  Back to cited text no. 21
    
22.Carlsson C, Johansson AK, Alvan G, Bergman K, Kühler T. Are pharmaceuticals potent environmental pollutants? Part I: environmental risk assessments of selected active pharmaceutical ingredients. Sci Total Environ 2006;364:67-87.  Back to cited text no. 22
    
23.Carlsen E, Giwercman A, Keiding N, Skakkebaek NE. Evidence for decreasing quality of semen during past 50 years. BMJ 1992;305:609-13.  Back to cited text no. 23
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24.Cserháti T, Forgács E, Oros G. Biological activity and environmental impact of anionic surfactants. Environ Int 2002;28:337-48.  Back to cited text no. 24
    
25.Velo G, Erice Statement 2009: Communication, medicines and patient safety. Br J Clin Pharmacol 2010; 69: 207-8.  Back to cited text no. 25
    
26.Kühler TC, Andersson M, Carlin G, Johnsson A, Akerblom L. Do biological medicinal products pose a risk to the environment?: A current view on ecopharmacovigilance. Drug Saf 2009;32:995-1000.  Back to cited text no. 26
    
27.Webb S. A data-based perspective on the environmental risk assessment of human pharmaceuticals I-collation of available ecotoxicity data and II-aquatic risk characterisation. In: Kümmerer K, editor. Pharmaceuticals in the Environment Sources, Fate, Effects and Risks. 1 st ed. Heidelberg, Germany: 7 Springer-Verlag; 2001. p. 175-230.  Back to cited text no. 27
    
28.Ferrari B, Paxeus N, Lo Giudice R, Pollio A, Garric J. Ecotoxicological impact of pharmaceuticals found in treated wastewaters: Study of carbamazepine, clofibric acid, and diclofenac. Ecotoxicol Environ Saf 2003;55:359-70.  Back to cited text no. 28
    



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