How to make pharmaceutical drugs less toxic to the environment?

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The last few years have seen the advent of a new eco-fear: the disturbing afterlife of pharmaceuticals. Drug residues excreted by humans and livestock linger in our waterways, often for months, before breaking down. The effects of these residues are difficult to isolate and poorly understood, but scientists have found evidence of problems. Some have found an alarming number of intersex fish – that is, fish whose testes contain eggs – in rivers laden with estrogen and estrogen-like compounds (from pharmaceuticals and other chemicals). Others have observed that antidepressants like Prozac can disrupt the maturation of frogs and hamper the minnows.

As the Associated Press reported in a widely read article in 2008 investigationeven our drinking water contains traces of many medicines. The quantities are infinitesimal and there is no evidence of danger to human health. But we don’t know how chronic exposure to even the lowest concentrations of these compounds, in unpredictable mixtures, might affect us – accurate testing of long-term consequences is essentially impossible. Based on the precautionary principle, not to mention the inherent nastiness of drug-contaminated water, vigilance is certainly in order. We have eco-friendly laundry detergent and remover, so why not develop greener drugs?

This is exactly what a handful of chemists are trying to do by learning from a few green drugs by chance while researching new strategies to reduce the environmental footprint of pharmaceuticals. Passionate people like Buzz Cue Jr. (a retired Pfizer scientist who is now an industry consultant) and Klaus Kummerer (a German chemistry professor) publishes articles and lectures at conferences, touting a new approach to pharmaceuticals that takes into account the post-cleansing phase. While companies have done a lot to reduce the environmental impact of drugs manufacturing– by reducing waste and using more harmless solvents, for example – they have done little to make drugs themselves more environmentally friendly.

Development “benign by design“Drugs pose a series of thorny challenges. In general, the qualities that make drugs effective and stable – bioactivity and resistance to degradation – are the same that cause them to worryingly persist after doing their job. And presumably even die-hard eco-martyrs (those who keep the thermostat at 60 all winter and forgo air travel) would be reluctant to sacrifice medical efficiency for the sake of aquatic wildlife. In addition, the molecular structures of pharmaceuticals are, in the words of chemist Carnegie Mellon Terry collins, “exquisitely specific.” Typically, you can’t just add a feature like greenery to a drug without affecting its entire design, including important medical properties.

Still, some drugs work well, but with minimal environmental impact. Glufosfamide, a treatment for pancreatic cancer, is incredibly biodegradable, as is valproic acid, an epilepsy drug. “Biologics,” which include insulin and vaccines, are made up of naturally occurring compounds (as opposed to synthesized compounds), so they easily break down in the environment. One of the greenest drugs turns out to be this little blue pill: the human body completely converts Viagra into much less powerful metabolites. * (Well over half of the antibiotic amoxicillin, on the other hand, passes through the patient unchanged.) Such drugs offer tantalizing clues that scientists may be able to apply to future formulas.

While trying to learn from these accidentally green drugs, scientists are also looking for new ways to keep minnows away from Prozac. Cue and others dream of a “magic switch” that would allow a drug to remain stable until it is released into the environment, at which point – presto! – it would become biodegradable. One way to do this is to make the drugs “photodegradable” with light-sensitive molecular triggers, which would cause the drug to break down in the waste treatment plant. Another possibility is to design a drug that is inherently less stable and attach it to a temporary stabilizer that would not break until it got inside the body. This research, however, is at the conceptual stage, far from reaching your local Rite-Aid.

Efforts to reduce drug dosages, a complementary tactic, have made more progress. Take, for example, a processing developing for osteomyelitis, a type of bone infection. Rather than flooding your whole body with antibiotics, the medicine uses a special molecule to transport the antibiotics directly to the site of infection. Likewise, several new cancer therapies can target malignant cells with greater precision than ever before. And researchers continue to improve “bioavailability,” that is, the proportion of the drug’s active ingredients that actually reach relevant patient tissues. All of these approaches allow for lower doses without compromising efficacy. This means fewer side effects for the patient and for the planet. (Caution: In some of these cases, although the doses are lower, the drug is more potent, which could negate the environmental gains.)

Today, companies have little incentive to make drugs that are more environmentally friendly, unless it coincides with other benefits that improve profits, such as reduced side effects. Drug design is laborious and expensive, and adding another criterion makes the task even more difficult. In Europe, however, politicians are starting to exert pressure: in 2006, the EU published guidelines for pharmaceutical companies to follow when assessing the environmental risk of new drugs. And since 2005, a government sponsored initiative Swedish database included information on the biodegradability, bioaccumulation and toxicity of drugs, so that physicians and patients can assess environmental friendliness along with other factors. The United States has also taken note of the problem. About every five years, the Environmental Protection Agency compiles a list of “candidate contaminants” for possible regulation. The most recent list, completed in 2009, for the first time recognized pharmaceuticals – nearly a dozen of them. That doesn’t necessarily mean the EPA will regulate the drugs, but it’s a signal to drug companies that the problem is on the government’s radar.

Until greener drugs hit drugstore shelves, we can take modest steps on our own to mitigate the damage by keeping the offending substances out of our medicine cabinets in the first place. Many drugs are a godsend, of course, but there is plenty of evidence that Americans are probably getting more of them than we need. Patients expect to leave the doctor’s office with a prescription, and doctors force, prescribing antibiotics dangerously. The practice of giving Zoloft and other psychoactive drugs instead of talk therapy has already triggered a backlash. If we could reduce the free and harmful use of drugs we would all be better off, and so would the minnows.As Slate to Facebook. follow us on Twitter.

Correction, January 19, 2011: An earlier version of this article stated that Viagra’s metabolites were relatively harmless. Definitive evidence of their potential for harm is not yet available. (Return to the corrected sentence.)



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