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 Table of Contents  
Year : 2021  |  Volume : 6  |  Issue : 3  |  Page : 149-152

A systematic review protocol examining the effect of environmental cardiovascular and antidiabetic agents on aquatic organisms and humans

Department of Pharmacology, PGIMER, Chandigarh, India

Date of Submission06-Aug-2021
Date of Decision07-Sep-2021
Date of Acceptance17-Sep-2021
Date of Web Publication22-Nov-2021

Correspondence Address:
Prof. Samir Malhotra
Department of Pharmacology, PGIMER, Chandigarh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jncd.jncd_45_21

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Context: Pharmaceuticals are released into the environment through human and industrial waste and waste due to handling. They significantly contaminate aquatic systems and through food chain, enter the body of human beings. The development of new techniques such as liquid chromatography and mass spectrometry has helped to detect and measure even the trace amounts of pharmaceutical compounds in the environment. At present, cardiovascular and antidiabetic agents are one of the most commonly prescribed drugs worldwide owing to chronicity of the diseases. However, there is a lack of knowledge regarding their effects on aquatic organisms and human beings once they are released into the environment.
Aim: The aim of the study is to identify the extent and characteristics of the toxicity caused by environmental cardiovascular and antidiabetic agents on aquatic organisms and humans.
Settings and Design: It will be systematic review of all original research articles which assess the environmental toxicity of one or more cardiovascular and antidiabetic drugs.
Methodology: This systematic review will be conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data regarding acute and chronic toxicities caused by cardiovascular and antidiabetic drugs to fish, daphnia, algae, and humans will be collected. In addition, we will report sampling strategies and methodologies adopted to quantify drugs from the samples.

Keywords: Cardiac drugs, ecopharmacology, ecotoxicology, hypoglycemic drugs, non-communicable diseases

How to cite this article:
Gamad N, Bhansali S, Malhotra S. A systematic review protocol examining the effect of environmental cardiovascular and antidiabetic agents on aquatic organisms and humans. Int J Non-Commun Dis 2021;6:149-52

How to cite this URL:
Gamad N, Bhansali S, Malhotra S. A systematic review protocol examining the effect of environmental cardiovascular and antidiabetic agents on aquatic organisms and humans. Int J Non-Commun Dis [serial online] 2021 [cited 2023 Mar 26];6:149-52. Available from: https://www.ijncd.org/text.asp?2021/6/3/149/330912

  Background Top

Between 2500 and 500 BC, ancient Hindu, Chinese, and Mediterranean civilizations used various medicinal drugs in their practice to relieve from pain. These medicinal substances were derived from natural extracts of herbs, plants, roots, vines, and fungi.[1] After World War II, chemical drug discoveries and usage developed rapidly to kill or immobilize microbes selectively which continued growing thereafter.[2] Following this rapid development, environment nowadays receives pharmaceutical products on a global scale through domestic, industrial, or hospital effluents and through effluents from waste water treatment plants, where pharmaceuticals are incompletely removed. The main trail pharmaceuticals follow to aquatic environment, thereby contaminate groundwater or surface water, which might re-enter into humans through food chains or drinking water.[3] Various investigators have reported the presence of numerous pharmaceuticals in wastewater. Since then, many improvements in analytical methodologies have facilitated the detection of very low concentrations of pharmaceuticals in surface water, wastewater, groundwater, and drinking water.[4] Hughes et al. reported that antibiotics, antiepileptics, and painkillers are the most studied compounds possibly due to frequent consumption worldwide. In contrast, other potentially toxic therapeutic classes such as cardiovascular and antidiabetic agents have not received much attention.[5]

The production and consumption of cardiovascular and antidiabetic drugs are on the rise corresponding to the increased incidence of cardiovascular disorder and diabetes worldwide. Several studies have investigated the acute and chronic effects of cardiovascular and antidiabetic drugs in the aquatic environment: for acute toxicity, concentrations that are likely to cause negative effects on aquatic organisms are detected in water.[6],[7] Despite the fact that there are not many studies on chronic toxicity, investigators found that antidiabetic drugs exhibit marked toxicity to human cells, even higher than that of the well-known poisonous metal, arsenic.[8]

Previous studies and reviews examining the occurrence of cardiovascular and antidiabetic drugs in environmental samples mainly emphasized on the analytical techniques applied to detect these compounds and their physicochemical properties that affect their presence in the aquatic environment.[9],[10]

Therefore, the aim of this study is to conduct an exhaustive systematic review of all available studies that have investigated the presence of cardiovascular and antidiabetic drugs in the aquatic environment to date, in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. In addition, the corresponding sampling strategies and methodologies adopted will be discussed in an effort to assess the quality and validity of the included studies.


  • To evaluate the characteristics of the toxicity caused by environmental cardiovascular and antidiabetic agents on aquatic organisms and humans
  • To assess the extent of the toxicity caused by environmental cardiovascular and antidiabetic agents on aquatic organisms and humans

  Methodology Top

This will be a systematic review of all original research articles which assess the environmental toxicity of one or more cardiovascular and antidiabetic drugs.

A preliminary literature search was conducted in PubMed, EMBASE, MEDLINE, and PROSPERO to look for any review with the same research question and objectives. After ensuring no such publications or registrations, a review protocol was written and registered in the PROSPERO (number of registration: CRD42021227667). We developed an inclusion criteria as per PICOT format as shown in [Table 1].
Table 1: Eligibility criteria for the systematic review

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Search strategy

The standard PRISMA checklist will be followed for the design, implementation, and reporting of this study. To identify as many original papers as possible, published or not, this review will be conducted through a search on PubMed, OpenGrey, and Web of Science using Medical subject headings (MeSH), or equivalent. All original studies written in English that assesses at least one cardiovascular or antidiabetic drug will be included. Initial screening will be done by two authors independently based on the title and abstract. Full texts of the studies that appear to meet inclusion criteria will be retrieved to substantially assess the eligibility criteria. Disagreement will be resolved through discussion with third author or consensus.

Data extraction

Once the study is included in our systematic review, following data will be collected and tabulated: the year of publication, country in which the study was conducted, compound tested, source of the sample, organism in which the compound was tested or determined, dose or concentration at which the compound was tested, duration of exposure and toxicity tests conducted and their findings. If the study identified direct environmental toxicity in any organism without conducting any laboratory tests or simulations, such data will also be collected and highlighted. Our preliminary search found that there are hardly any studies which have assessed direct environmental toxicity on humans. Hence, we will draw implications on humans from the findings of the selected studies conducted on organisms as mention on the selection criteria.

Data collection and analysis

The results obtained from the searches will be screened for relevance, and eligible studies will be selected for inclusion against the predefined inclusion/exclusion criteria. Two reviewers (NG and SB) will then independently extract data from the studies selected for inclusion using a data extraction form, and the third reviewer (SM) will cross-check the data.

Risk of bias within and across studies

Cochrane's risk of bias tool will be used to assess the risk of bias among included studies, if applicable.

Statistical plan

Where data allows, a meta-analysis will be undertaken using RevMan. Detailed narrative synthesis of the results will be done for each drug tested against different aquatic organisms. The findings will be detailed as per each organ system and implications for humans will be drawn.

  Discussion Top

Many individual studies suggest that pharmaceutical products persist in the environment in concentrations enough to cause toxicity in target and nontarget organisms. In a meta-analysis, Lopes et al.[11] highlighted that antidepressants contaminating the aquatic environment produce negative effects on reproductive systems of crustaceans. Exposure to antibiotics in food chains caused by unaltered access to sewage is known to cause alteration in the microbial community, antimicrobial resistance, and lethal infections in humans.[12] In the drug regulatory process, most of the emphasis is on assessing safety and efficacy in humans. Although the sponsors are obliged to provide data on environmental impact assessments of their compounds before seeking regulatory approval, the process is not fool-proof and the compounds are usually certified by laboratories which are funded by sponsor themselves.[13] In developing countries like India, there are multiple problems-huge population, increased burden of cardiovascular diseases and diabetes-rightly called as “diabetes capital of the world,” increased consumption of drugs treating those diseases, increased number of manufacturing companies, less attention to sewage treatment, among others-together increase the presence of drug in the environment. Hence, we planned this research to generate comprehensive evidence on environmental impact of most commonly prescribed medications-cardiovascular and antidiabetic drugs. The results of this review may help to formulate stringent policies against the management of industrial waste and sewage.

  Conclusion Top

Significant toxicity is caused by drugs released to environment, most so by commonly prescribed drugs such as cardiovascular and antidiabetic drugs. Since systematic reviews stand at the top most layer of pyramid for evidence generation, this study will ascertain the details of the environmental toxicity caused by such drugs and will help generate policies for sewage management and treatment of effluents.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Pharmaceuticals. Encyclopedia Britannica, 2008. Available from: http://global.britannica.com/topic/pharmaceutical. [Last accessed on 2021 Aug 02].  Back to cited text no. 1
Pharmaceutical Sciences University of California Irvine-Irvine, CA 92697: 949-824-5011. 2011. Short History of Drug Discovery. Available from: http://https://pharmsci.uci.edu/programs/a-short-history-of-drug-discovery/. [Last accessed on 2021 Aug 02].  Back to cited text no. 2
Cooper ER, Siewicki TC, Phillips K. Preliminary risk assessment database and risk ranking of pharmaceuticals in the environment. Sci Total Environ 2008;398:26-33.  Back to cited text no. 3
World Health Organization (WHO). Pharmaceuticals in drinking-water. 2012. Available from: https://www.who.int/water_sanitation_health/publications/2011/ pharmaceuticals_20110601.pdf. [Last accessed on 2021 Aug 05].   Back to cited text no. 4
Hughes SR, Kay P, Brown LE. Global synthesis and critical evaluation of pharmaceutical data sets collected from river systems. Environ Sci Technol 2013;47:661-77.  Back to cited text no. 5
MacLaren RD, Wisniewski K, MacLaren C. Environmental concentrations of metformin exposure affect aggressive behavior in the Siamese fighting fish, Betta splendens. PLoS One 2018;13:e0197259.  Back to cited text no. 6
Sumpter JP, Runnalls TJ, Donnachie RL, Owen SF. A comprehensive aquatic risk assessment of the beta-blocker propranolol, based on the results of over 600 research papers. Sci Total Environ 2021;793:148617.  Back to cited text no. 7
Zhang R, He Y, Yao L, Chen J, Zhu S, Rao X, et al. Metformin chlorination byproducts in drinking water exhibit marked toxicities of a potential health concern. Environ Int 2021;146:106244.  Back to cited text no. 8
Zhou Y, Meng J, Zhang M, Chen S, He B, Zhao H, et al. Which type of pollutants need to be controlled with priority in wastewater treatment plants: Traditional or emerging pollutants? Environ Int 2019;131:104982.  Back to cited text no. 9
Godoy AA, Oliveira ÁC, Silva JG, Azevedo CC, Domingues I, Nogueira AJA, et al. Single and mixture toxicity of four pharmaceuticals of environmental concern to aquatic organisms, including a behavioral assessment. Chemosphere 2019;235:373-82.  Back to cited text no. 10
Lopes DG, Duarte IA, Antunes M, Fonseca VF. Effects of antidepressants in the reproduction of aquatic organisms: A meta-analysis. Aquat Toxicol 2020;227:105569.  Back to cited text no. 11
Singer AC, Shaw H, Rhodes V, Hart A. Review of antimicrobial resistance in the environment and its relevance to environmental regulators. Front Microbiol 2016;7:1728.  Back to cited text no. 12
Jena M, Mishra A, Maiti R. Environmental pharmacology: Source, impact and solution. Rev Environ Health 2019;34:69-79.  Back to cited text no. 13


  [Table 1]


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