When covid-19 began spreading in 2020, humans around the world were fed 4. 5 trillion doses of a myriad of pharmaceuticals. In 2021, 3500 million tablets of a single drug were sold in India alone: paracetamol, a painkiller used to treat some symptoms of covid-19. Big Pharma shifted gears as corporations rushed to expand effective vaccines and reach the market, distributing more than 12. 6 billion doses in record time.
But long before COVID-19 hit, new and existing drugs were being produced at a breakneck pace, a trend that is sure to grow in the future. In the next five years, drugmakers could introduce three hundred new drugs, according to fitness study company IQVIA. Predicted.
However, medications, even life-saving ones, in position and doses can be contaminants.
These chemical concoctions that enter the human bloodstream and alleviate much of the human suffering end up seeping into the veins of the Earth, into rivers, lakes and estuaries, with scientists largely ignorant of the evils potentially generated in this larger wild world.
A global study published this year found that rivers everywhere, including Antarctica, are infected with pharmaceuticals. Alistair Boxall and his colleagues analyzed samples from 1,000 sites in more than a hundred countries, looking for 61 active pharmaceutical ingredients, the must-haves that turn mundane compounds into medicines.
More than 4000 active ingredients from the pharmaceutical industry are currently used. All are compounds designed to elicit a biological response, to manipulate the functioning of living organisms. This fact means that active ingredients from the pharmaceutical industry released into waterways have the potential to harm the environment.
The initial findings of Boxall’s team indicated that concentrations of at least one active pharmaceutical element exceeded levels of protection from aquatic life at a quarter of the sites studied. A follow-up study published in June suggests that this number may be higher, closer to 40%. if a wider diversity of affections is taken into account.
These statistics show staggering clinical oversight, says Boxall, a professor of environmental science at the University of York in the United Kingdom. He says he’s disappointed that now, decades after many drugs were first widely used, they continue to be classified as “emerging contaminants. “
“It’s only in the last 10 to 20 years that it began to be recognized that prescription drugs can harm the environment,” he said.
Of the 61 active pharmaceutical ingredients evaluated, some continued to appear repeatedly. Among the most ubiquitous in the world’s waterways were carbamazepine, used to treat epilepsy, as well as caffeine, a stimulant, and metformin, a first-line drug for type 2 diabetes prescribed through doctors and used through patients around the world.
Mongabay to take a look at just one of those three, opting for metformin, not because it stands out as a harmful pollutant, but because its environmental pathways and our false impression of its ecological effects illustrate other highly prescribed pharmaceuticals.
About 90% of other people diagnosed with diabetes have type 2 diabetes, where the body gradually loses its ability to use insulin, a hormone produced by the pancreas. Insulin helps cells absorb sugar in the form of glucose from the blood. But insulin resistance leads to high blood sugar levels. Over time, too much sugar in the blood can damage important organs such as the kidneys, weaken nerves, and in excessive cases, lead to blindness or loss of limbs.
Metformin hydrochloride, or 1,1-dimethylbiguanide hydrochloride, is the most widely prescribed diabetes drug today. The exact mechanism by which it lowers glucose levels is unknown. Absorption of glucose in the intestine. Like many medications, it has a litany of effects that vary from patient to patient.
Metformin was synthesized in a laboratory in Dublin, Ireland, in 1922, but it wasn’t until 1957 that French physician Jean Sterne first reported its hypoglycemic properties. The decades from 1940 to 1960 saw an increase in its medicinal use worldwide, which corresponds to an explosion of the release of new drugs, to which is added the massive distribution of antibiotics.
While other countries approved metformin for the treatment of diabetes, the United States did not do so until the mid-1990s. Regulators acted cautiously after a debacle with another diabetes drug: phenformin. Phenformin was linked to severe lactic acidosis, or accumulation of acid in the blood, resulting in thousands of deaths in the United States in the 1960s and 1970s.
Concerns about human protection have naturally remained at the heart of drug development. But ecological considerations have figured prominently in metformin’s global approval, and environmental damage is rarely a barrier to approval of new drugs in most countries today.
This truth now leads scientists to ask the question: how much of a pharmaceutical product, or a mixture of those contaminants, can result in an overdose for a river system?
The answer is that we simply don’t know and knowledge is very scarce.
Despite its global reach, the Boxall team’s initial survey captured the footprint of active pharmaceutical ingredients for just 471 million people, without assessing any express harm. year – and watercourses.
The expansion of the human population since World War II has resulted in a growing demand for drugs around the world, especially in countries where incomes have risen more recently. . Other non-unusual denominators of the spread of pollution come with the simple and widespread acceptance of drugs across the planet.
India, for example, is now the world’s third-largest pharmaceutical manufacturer by volume, which has earned it the nickname “the world’s pharmacy. “no longer through patents). The resulting less expensive drugs are easily found in the Indian domestic market, while they are also shipped worldwide. About 40% of generic formulations sold in the U. S. UU. se provided through India, according to one estimate.
While most people associate medical waste with hospitals, medical services are not, in fact, the most important source of pharmaceutical contamination. Although drug production plants generate waste containing active pharmaceutical ingredients, families are the largest source of pharmaceutical contaminants.
Which brings us back to metformin. India is currently home to the largest number of other people with diabetes after China: 80 million in total, more than the entire French population. In Delhi, a city of nearly 20 million people, an estimated 25-33% of the population suffers from diabetes, and many are metformin users.
Those who take the ubiquitous diabetes drug are inadvertently polluting its important water source, the Yamuna River, which irrigates much of northern India’s crops.
“Any replacement in a company’s use of drugs will influence what we see in a river,” Boxall explained. In fact, many pharmaceutical compounds, in addition to metformin, pass through the human body without losing their potency and are completely metabolized. In fact, more than two-thirds of a dose of metformin can end up intact in urine or feces.
And most of it goes directly through medicinal plants.
According to India’s leading pollutant control agency, wastewater is the main pollutant of India’s waterways. They are treated.
Delhi is an exception in this regard, with the capacity to treat 80% of its waste. However, according to government data, 24 of the capital’s 34 wastewater treatment plants did not meet wastewater treatment criteria in 2021. The Yamuna receives the maximum wastewater from the megalopolis.
Despite being among India’s best-equipped waste-fighting facilities, the capital’s wastewater treatment plants are not designed to extract pharmaceutical contaminants. The researchers detected a cocktail of 22 active pharmaceutical ingredients, in addition to metformin, in river water samples taken in the capital region. According to the new study, Delhi had some of the highest average concentrations of active pharmaceutical ingredients in the world, along with Addis Ababa in Ethiopia, La Paz in Bolivia and Lahore in Pakistan.
Studies like those published by Boxall’s team fill a gap. The parts of the planet that, so far, have gained the least attention in mapping pharmaceutical contaminants (South America, sub-Saharan Africa and parts of South Asia) are proving to be among the most affected.
Lagos in Nigeria, sub-Saharan Africa’s most populous city, is a hotbed of pollution, with 26 pharmaceutical compounds detected in the Odo-Iya Alaro River. “There are no restrictions on who can open a pharmacy,” explained Charles Obinwanne Okoye, an environmental biologist at the University of Nigeria, “and other people can buy medicines without a prescription. “
“It’s first and foremost a waste control problem,” Okoye said, with woefully inadequate wastewater treatment systems in countries where pharmaceutical use was rampant.
The same households that manufacture the drugs in the target organism (humans or livestock) can turn them into harmful ecological pollutants, especially in waterways where other water users are exposed to them.
Downstream of Delhi’s Yamuna River, informal settlements use water for their needs, including, in some cases, drinking. They also use river water to irrigate crops, as prescription drugs can contaminate the food supply.
Direct exposure can also be harmful to wildlife. In clinical studies, brown trout (Salmo trutta) exhibits behavior similar to methamphetamine, known as methamphetamine. But fish dependence on illicit drugs is not the only problem.
Some prescription drugs are a subset of a wider variety of chemicals called endocrine disruptors, which mimic hormones and interfere with the endocrine system. These chemicals are found in everything from plastic bottles to pesticides, and are also used in prescription drugs.
Metformin would possibly also fall into this category. Although the diabetes drug does not structurally resemble traditional endocrine disruptors, it is becoming increasingly popular “that endocrine disruption can occur through mechanisms other than classical binding to endocrine receptors. “According to some studies, metformin produces “extensive and unknown changes” in fish. , mammals and invertebrates.
The scientists found that when fat-headed piscardos (Pimephales promelas) were exposed to degrees of metformin equivalent to those found in wastewater, male fish showed symptoms of feminization, some men were abnormally small, and the drug also affected fish reproduction. However, other studies have not captured effects on the species.
Some experts argue that when it comes to endocrine disruptors, higher doses don’t mean greater effects. They say there is no unequivocal and undeniable correlation between dose duration and impacts. Therefore, the traditional justification for determining limits for environmental pollutants would possibly not apply to endocrine disruptors. In some cases, lower doses can produce effects very different from the concentrations studied in laboratory experiments.
This low-dose effect is also manifested in other types of prescription drugs similar to antimicrobials. Disease-causing pathogens, as well as bacteria, viruses and fungi, can evolve in the human body and in nature to antibiotics designed to attack them. This happens primarily through their exposure to medical compounds that evolved to kill them, with a subset of the surviving pathogenic population likely immune to the antibiotic, an evolved trait that is passed on to offspring.
Sulfamethoxazole is an antibiotic and expansion promoter for livestock. It is also a non-unusual contaminant. Today, their effectiveness is largely undermined, with bacterial targets becoming resistant.
It is important to note that toxic levels of antibiotics are not required to produce significant antimicrobial resistance. Even lower doses, such as those potentially found in waterways, can build resistance by allowing microbes to become familiar and adapt to a threat.
This “silent pandemic” of microbe-resistant infections stealthily empties the medical arsenal of antibiotics accumulated over decades. A study commissioned by the UK government estimated that deaths from antimicrobial resistance infections could amount to just 10 million by 2050. Antimicrobial resistance is already wreaking havoc in India, where access to physical care is poor. More than 50,000 newborns die there each year from drug-resistant infections.
Despite their destructive potential, active pharmaceutical ingredients have remained poorly studied and regulated.
“Pharmaceutical pollutants are an example of scary chemicals that fall outside the scope of existing foreign treaties that apply to chemicals and waste,” said Mirella Miettinen, an environmental law specialist at the University of Eastern Finland.
Miettinen is one of the principal investigators of the LDS project, which aims to reduce life-cycle environmental hazards of pharmaceuticals.
Despite the growing awareness of scientists, there are no systematic reports on the effects of medicines on ecological health. This is true in countries where there is a steady expansion in the use of pharmaceuticals, combined with poor waste management. But that’s not a limited amount of time for “pharmaceutical” economies, as countries like India, China and Brazil call it in industrial jargon.
Boxall reports that of the roughly 2,000 prescription drugs used in Europe, less than a fifth of the knowledge about ecological effects is available. Sweden is a pioneer on this front. The Scandinavian country brought an environmental classification formula for prescription drugs in 2005.
The risk-benefit investigation conducted through EU regulators when authorising a new medicine takes into account environmental risk, Miettinen ed. Meanwhile, the U. S. FDA. The U. S. Food and Drug Administration has the authority to deny applicants sufficient data on the environmental effects of a new drug. medicament. However, a plethora of approval exceptions means that environmental testing is the norm for new drug applications.
Experts like Miettinen argue that regulators deserve to take environmental effects into account when authorizing new prescription drugs and limiting the use of a drug that carries the greatest environmental risk.
Similarly, overprescribing and misuse of prescription drugs will need to be controlled. Much more studies are also needed on the effects of single drugs and multi-drug interactions on waterways around the world.
But even knowing what the effects are wouldn’t be enough. Take metformin, for example. It is an essential first-line drug; Consumers and healthcare providers can’t seamlessly replace a “greener” version. To do this, a company finds it financially advantageous to produce one that is just as efficient, verify it safely, and make it available – a lengthy and expensive process.
“We want moves in other degrees to solve the problem,” Miettinen said, adding “creating incentives for the progression of compounds with improved biodegradability. “
Once we enter the market and our bodies, tracking becomes much more complicated.
Regulation of contaminants at production sites is a reasonable blow, and commercial waste control frameworks come with pharmaceutical manufacturers. “The pharmaceutical industry is a highly polluting industry that belongs to the red category,” said Gopal Krishna, an India-based environmental activist. they are industries that generate hazardous waste. “
Hospitals are well placed to adopt the processing of active pharmaceutical ingredients before they enter the public wastewater stream. Several technologies are being tested lately to remove active pharmaceutical ingredients in hospitals, many of them in Europe.
But household waste is much more sensitive to treat. For the most industrialized countries, this means comprehensive improvements to wastewater infrastructure. For less industrialized countries, the procedure deserves to start with the structure of waste treatment services, with developers stepping up to install complex water remedies. technologies, some of which are now considered too expensive even for the richest countries.
Metformin back provides a clever example of inherent problems. It is already ubiquitous in the water supply, even in industrialized countries such as the United Kingdom and the United States, because traditional remedy strategies cannot eliminate it.
Radboud University Medical Center in the Netherlands partnered with Dutch company VitalFluid on strategies to extract pharmaceutical waste from hospital wastewater. They were based on a complex oxidation procedure that increases reactive oxygen and nitrogen. Even then, metformin turned out to be a persistent contaminant to extract.
“Solutions like activated carbon filters or ozone remedies will degrade many more pharmaceuticals,” Boxall explained. “The reason is that they are expensive. “
The installation of such systems on a large scale will weigh heavily on taxpayers. More than a decade ago, upgrading a single Canadian processing plant to treat biological waste and prescription drugs costs more than Rs 2. 44 billion. Last July, the Delhi government approved one million rupees to plug the Yamuna River. The government plans to use the cash to identify new sewer lines, build 10 new wastewater treatment sets and upgrade six existing treatment plants.
Clearly, achieving the purpose of fully assessing and managing global pharmaceutical contaminants well is in the future.
This article was first published on Mongabay.
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