Wednesday, November 28, 2007

Greenpeace Guides the Way for e-waste

What to buy if you’re compelled towards holiday consumerism, yet feel just a twinge of guilt when you pick out the latest hot-pink cell phone or the must-have computer game-console?

Fear not, dear consumer. Greenpeace just released its “Guide to Greener Electronics.” Although the truly greener thing would be to hang on to the old phone or out-dated uncool game device until the bitter end, and then choose not to replace - that's a bit idealistic these days. At the very least, you can now figure out how to recycle the thing, and perhaps replace it with a more environmentally friendly model.

Ratings are based on reduction of hazardous materials (and intent to reduce hazardous chemicals in the future) in production and ease of recycling. Criteria include elimination or phase-out of persistent organic flame-retardants such as polybrominated biphenyls, producer take-back programs and transparent information on amounts of recycled product. What’s not clear is if recycling practices (what happens once they collect the stuff) are evaluated as well.

One particularly useful feature of the report are the links to recycling programs for each brand. So, by following the links I could finally print out a Waybill for that Dell computer I threatened to send back to Michael Dell several years back - but then decided it wasn't worth spending another dollar on that lemon. Every major component had to be replaced before its second birthday. It has spent the last two years hiding under our futon couch just waiting for this moment. Though I’d never again buy a Dell, they ranked pretty high with a 7.3 on the 10-point scale. That places them in a tie, for fourth highest score. The loser was Nintendo with an astounding ZERO points!

Tuesday, November 27, 2007

Even more on grapefruit juice

Ok, this is it. One last word on grapefruit juice. As both JLowe at Impact Analysis and my sister who actually reads the Wall Street Journal just informed me, grapefruit juice is now being pharmacueticalized if there is such a word. That is, someone's finally decided to capitalize the inhibitory potential of grapefruit juice extracts.

You can read a more detailed analysis at Terra Sigillata who suggests that trying to boost drug activity (and minimize dose) may be asking for trouble.
But then, as the WSJ article suggests there are some cases where boosting the efficacy of a poorly absorbed drug might be advantageous.

My take - after all this discussion of drug interactions - is why add yet another drug (unless absolutely necessary) when it's clear as Terra suggests that we're not only looking at combining drugs but also interindividual differences in how each body handles drugs - which depends on many factors including genetics, nutrition, gender, age, etc.

Monday, November 26, 2007

More on grapefruit juice and drugs

A few weeks back, I wrote about drug interactions. On the recommendation of my editor (it was originally for the local paper,) I'd removed the details of how certain drugs are metabolized - the part I found most interesting, and the part he thought would most likely lead to bored and frustrated readers.

At the time I'd agreed with him and cut. But then, over the Thanksgiving Holiday, when I'd jokingly commented on the cranberry juice cocktail my friend was about to finish off, she said,

"...but I only take the Lipitor at night. Drinking a glass of cranberry juice during the day shouldn't matter."

Maybe, maybe not. I don't know much about the combination of Lipitor (atorvastatin calcium) and cranberry juice but the comment reminded me of why I'd written about the details of drug metabolism in the first place.

While the science of drug metabolism is complicated enough, when one adds the potential for drug-drug or drug-food interactions the level of complexity can skyrocket.

First, a quick introduction to drug metabolism. Lipitor is a drug metabolized primarily by enzymes belonging the CYP detoxification or drug metabolizing system. Years ago the CYP system was one of the few recognized detoxification systems in the body. That is, a collection of enzymes working together to metabolize toxic chemicals and send them on their way before they can cause any damage. Back then we knew of only a couple of enzymes, now there are dozens and dozens grouped into "families" of CYP enzymes. In the case of Lipitor, CYP3A4 is key for proper metabolism and eventual excretion of the drug.

For chemicals that require metabolism by CYP enzymes prior to excretion, the CYPs play an important role in determining the half-life of a drug or chemical.

Half-life refers to the length of time required for a drug or chemical to be reduced to one-half the initial concentration. Knowing the half-life is necessary to determing dosage ensuring that 1) there is sufficient levels of drug in the system and 2) concentrations don't get too high that they become toxic.

Anything that screws with the half-life of a chemical is potentially very dangerous. For chemicals that must be metabolized in order to be excreted, an increase in CYP metabolism would reduce half-life, resulting in drug concentrations that may no longer effective. Conversely, a reduction of CYP metabolism, or inhibition of metabolism can increase half-life, causing drugs to accumulate to toxic, possibly even lethal concentrations.

And even asking "what's the half-life" of a drug under normal conditions isn't so simple. Take the example of Lipitor. While the parent compound Lipitor (the actual drug that you ingest) may have a half-life of only fourteen hours, the metabolites of the drug - which in this case are most active - have a much longer half-life of twenty to thirty hours. That means that it can take up to thirty hours for half the initial concentration of active metabolites to exit your body.

Now lets consider the interaction between grapefruit juice (really certain chemicals in grapefruit juice) which act as inhibitors of CYP3A4. In this case, those CYP enzymes responsible for metabolic breakdown of Lipitor would be inhibited, essentially extending the half-life of the drug possibly leading to potentially toxic concentration of the drug.

And, what makes this all really complicated is that depending on how an inhibitor like grapefruit juice does it's dirty-work, the inhibitory effects may either very short-term or can last for days. In the case of grapefruit, according to one article in Pharmacy Times drinking grapefruit juice not only has immediate (within 30 minutes) impacts on metabolism, but, depending on how long and how much one has been drinking, inhibitory effects can last up to three days. This is because the chemicals responsible for inhibition by grapefruit juice, essentially combine irreversibly to CYP3A4, taking them out of action for good, necessitating synthesis of new enzyme.

Phew - maybe my editor was right! Well, you get the point I hope.

When taking new drugs or adding new food and beverages to your diet, it's well worth the little extra effort to inform your doctor or your pharmacist of the changes.

Wednesday, November 14, 2007

Environmental Impact of Clothing Revealed

It's not easy finding information on the waste products, the energy used, or the carbon dioxide produced by your favorite shoe manufacturer or clothing company, but that's exactly what Patagonia (you know, the expensive but generally well-made and stylish outdoor adventure clothing company) does on their site, called the "Footprint ChroniclesTM ."

Of course not many of us really want to know. But this winter I'll be working with students at a local high school building a website that focuses on the environmental impacts of their favorite outfits. When I came across the Patagonia site, I knew I had my model.

They highlight a few key products (an organic cotton t-shirt, a waterproof shell, a wool sweater and a leather shoe,) covering the major categories of textiles, and provide details on the carbon dioxide production, energy use, and waste production.

For example according to the site, fiber for the cotton T originated in Izmir Turkey, traveled to Bangkok for spinning and sewing and then on to Reno, Nevada for distribution, traveling 14,100 miles, and generating 27 pounds of CO2 (remember this is a gas!), ten ounces of waste, and using enough electricity to power an 18w compact fluorescent bulb for 72 days.

After trying in vain to gather information on the ubiquitous Crocs ( a couple of emails to Tia Mattson their public relations manager asking questions about recycling and the chemistry of crosslite (PCCR) the primary material - only left me waiting by the phone for her call which never came), the apparent openness of Patagonia was a welcome find.

Of course, ever the skeptic I tried to find the holes. What about tanning? What about other toxics surely used in dying processes? Well, I couldn't find much on dying, but on their discussion page, readers did raise questions about tanning, and, the "localcrew" responded to reader's comments with seemingly honest and useful information. Patagonia also notes that although they still use PFOA in their "Eco-Rain Shell" they are seeking alternatives to the persistent environmental contaminant. Finally, a closer look at endpoints like "waste generated" reveals that this includes only solid waste, and not liquid or hazardous waste.

At the very least, it'll be a great place for students to begin, for in addition to maps and videos of manufacturing locations, they also provide detailed references which include several websites on Life-cycle analysis for various materials, energy use, and CO2 emissions.

Check it out, and thank you Patagonia for doing (at least part of) my howework!

Friday, November 09, 2007

Bindeez and Aqua Dots

As many are aware by now, there's been a lot of interest in Bindeez beads, the toy beads that can turn toxic if or when ingested. I first read about this in the New York Times, which reported how doctors treating a comatose child in Australia, first discovered that a solvent used in production of the beads, once ingested, can be metabolized into the infamous date-rape drug, GHB.

According to news reports, ingestion of these beads have led to additional hospitalizations, both in Austrailia and here in the U.S. where the beads were sold as Aqua-beads.

Both countries have issued recalls or bans for the products.

That industrial solvent, 1,4-butanediol according to an article by Rueters was apparently used by some manufacturers in China, in place of the less potentially toxic solvent 1,5-pentanediol. The intense news coverage has led
Science blogs to name 1,4-butanediol "Molecule of the Day."

Scienceblogs provides brief description of how our alcohol-metabolizing enzymes convert the industrial solvent 1,4-butanediol into GHB. There's also an interesting educational site about the conversion of 1,4-butanediol at Neuroscience for Kids.

Tuesday, November 06, 2007

Drug Interactions: more common than you might think

Many years ago, my father suffered a TIA or transient ischemic attack – a sort of mini-stroke. This episode occurred in association with a very common type of cardiac irregularity called atrial fibrillation. And what should have been a relatively short hospital stay turned into an all too real example of the adverse effects resulting from multi-drug interactions.

Following the TIA, thanks to a quick response by the local ambulance company, by the time my father reached the hospital he was relatively symptom free. A fact apparent to all but the admitting doctor who, upon checking for impaired mental capacity, asked him to recite the months backwards, beginning with the current month.

He said, “Enuj.”

It was the month of June, and that was my dad.

But as doctors struggled to find a safe and effective dosage of Coumadin (known generically as warfarin), a common blood thinner used to prevent future and more severe blood clots that can cause TIAs and worse, my dad’s blood levels of Coumadin bounced around, predictably unpredictable, thanks in part to his well developed drug metabolism system. You see, in his early twenties, following a bout of spinal meningitis, my father was diagnosed with epilepsy. For the rest of his life, he relied upon a combination of Meberal and Tegretol, two powerful medications to keep the seizures at bay.

Meberal is a derivative of phenobarbital, a drug that I’d been using in the toxicology laboratory at that time to increase the amounts of specific drug metabolizing enzymes. Tegretol will do the same. These enzymes belong to a system of detoxification enzymes that essentially alter toxic chemicals into more excretable compounds sending them on their way out of the body before they can cause any damage. Most likely, it was those same enzymes, induced by years of Meberal and Tegretol, which wreaked havoc with my father’s early Coumadin levels, measured then as “pro-time”, or anticoagulant activity.

To be fair, Coumadin is one of the most difficult drugs to manage, in part, because it is so susceptible to interactions with other drugs and nutrients (more on that later). Says Ed Tessier Pharm.D, and clinical pharmacist at Baystate Franklin Medical Center in Greenfield, MA, “It’s a life saving drug, but it’s known nationally as one of the most difficult to manage, not only because of drug interactions but genetics as well.” As with most biological systems, there is a strong genetic component of the detoxification system. Some of us are rapid metabolizers, some of us are not.

But here’s the thing. Although many of us don’t think we’re prime candidates for Who Wants to Host a Complex Drug Interaction, many of us do occasionally ingest potentially toxic combinations of drugs and chemicals in our food and drink without a second thought. Sometimes one of these combinations render drugs ineffective, sometimes it turns them toxic.

Take caffeine and Tylenol (or acetaminophen) for example. Acetaminophen is one of those drugs metabolized by the liver enzymes mentioned above and according to an article published online by eMedicine by Dr. Susan Farrell, assistant professor in the Department of Emergency Medicine at Harvard Medical School, “Acetaminophen is the most widely used pharmaceutical analgesic and antipyretic agent in the United States and the world….. As such, acetaminophen is one of the most common pharmaceuticals associated with both intentional and accidental poisoning.”

Most of the time, most of the acetaminophen we ingest is metabolized by specific detoxification enzymes to nontoxic by-products or metabolites, which we excrete without a problem. But sometimes, depending on the amount ingested, or, since we are talking about drug interactions, whatever else we may have ingested prior to, or along with the acetaminophen, some of it takes the toxic route, resulting in highly toxic metabolites. If you’re a cat owner, this may sound familiar. Acetaminophen and cats are a potentially lethal combination because in cats, unlike in humans, most acetaminophen is routinely metabolized via this toxic route.

Since most of this drug metabolizing drama takes place in the liver, it is the liver that is most susceptible to toxic metabolites. Notes Farrell, “In the United States, acetaminophen toxicity has replaced viral hepatitis as the most common cause of acute hepatic failure, and it is the second most common cause of liver failure requiring transplantation in the United States.”

Now say we drink a few too many Starbucks Grandes in addition to ingesting a hefty dose of Tylenol. According to Dr. Sidney Nelson, Professor of Medicinal Chemistry at the University of Washington, and lead author of a recent article in Chemical Research and Toxicology on the interaction between APAP and caffeine, “…very high concentrations of caffeine (the amounts individuals might achieve by drinking approximately 20 cups of coffee) can triple the amount of a liver toxic metabolite of acetaminophen.”

Twenty cups? That seems like an awful lot, although these days between high-test coffee and higher-test energy drinks, it would be wise for those heavy drinkers to take note. Not only that, but if one were to add a night of excessive drinking (this time I mean alcohol), followed by a morning requiring Tylenol and caffeine, it may not take twenty cups before your liver begins to suffer the consequences.

Says Dr. Nelson “…There is a period of 12-36 hours [after acute alcohol consumption] during which more acetaminophen toxic metabolite will be formed because of increased amounts of the metabolizing enzyme.”

You see alcohol, like my dad’s anti-seizure drugs also increases specific enzymes involved in certain detoxification (sometimes toxification) systems. And unfortunately, it’s not just “recreational drugs” like caffeine and alcohol that can interact with other drugs in potentially devastating ways. For a few years following my father’s TIA, after doctors figured out the correct Coumadin dosage, his blood levels of the drug remained relatively stable. He was an extremely attentive patient, interested in tracking levels of the drug as the doctors made them available, well aware of potential interactions of drugs and diet.

Then one day his Coumadin level shot up. This time, his medications weren’t to blame, nor was his overactive liver. Something was inhibiting the metabolism. The culprit, doctors eventually discovered, was his latest favorite beverage, grapefruit juice. Once again, my father’s real-life experience reflected what I had learned in toxicology. To inhibit detoxification enzymes in some of our experiments, we had used quercitin, one of the active substances in grapefruit.

According to Ed Tessier, for most Coumadin patients grapefruit juice may not be as important as other food and drug interactions, however, “grapefruit does affect metabolism of a great number of other drugs, including most of the “statin” drugs to lower cholesterol (such as atorvastatin – Lipitor®) and can lead to rhabdomyolysis - a life threatening condition which results in muscle tissue injury and possible kidney failure.”

As we add new foods to our diet, and new pharmaceuticals and herbal remedies to our medicine cabinets the potential for interaction is never-ending. One more product I am compelled to mention is St. John’s Wort, the herbal remedy commonly used to treat depression, also induces detoxification enzymes.

According to Nelson, “Chronic ingestion of St. John’s Wort….may increase the formation of the toxic metabolite of acetaminophen. If acetaminophen is taken in therapeutic doses, it is very unlikely that there would be any problem. However, if the individual taking these drugs takes larger doses of acetaminophen and drinks large amounts of caffeinated beverages (say 8 cups or more of strong coffee) or takes large amounts of caffeine-containing drugs, they would form significantly more of the toxic metabolite that could put them at risk of liver damage.”

And, among the many medications that may fall prey to enzymes induced by St. John’s Wort are most antidepressants, as well as many migraine medications, HIV medications, and birth control pills. Only in the case of some of these drugs -- including birth control pills -- the result of increased metabolism isn’t increased toxicity, but reduced efficacy.

Should this brief lesson in drug interaction scare you off your meds, fear not. These days, doctors like Kathleen McGraw MD, Medical Director of Hospital Medicine at Baystate Franklin Medical Center are blessed with instant access to reams of information on drug interactions through the web some of which can be downloaded onto hand held computing devices.

Within minutes of my mentioning St. John’s Wort, McGraw was on her PDA running the Epocrates program, scrolling through lists of drugs known to be adversely impacted by St. John’s Wort. Just as quickly she rattled off drugs affected by grapefruit juice.

To avoid problems caused by the potent chemicals in grapefruit juice, says McGraw, “I tell patients they need to give it up totally (same with cranberry juice) unless it is something they can't live without in which case they have to commit to having the same amount every single day. Given that choice, everyone says they'll quit.”

Adds McGraw, “I encourage every patient on Coumadin to remind any physician giving them a prescription for a new medication (especially antibiotics) about the Coumadin and ask if it will be affected.”

Thankfully, since the days of my dad’s TIA, the science and the awareness of drug-drug and drug-food interactions have come a long way. But it’s a two-way proposition. For pharmacists and doctors to do their part, we have to do ours, whether it’s disclosing that we’re on Coumadin, Viagra, birth control pills, herbal medications, Starbucks Grandes or the newest favorite, pomegranate juice.

UPDATE March 2010: it is well known that individual metabolic differences can dramatically impact drug metabolism. Particularly important for drugs like warfarin (coumadin.) A recent study shows that by tailoring doses based on genetic testing may help reduce hospitalizations due to drug imbalance. Read more here:

Reprinted from the Montague Reporter, please feel free to quote using proper attribution.

Saturday, November 03, 2007

Back to the Tap

The following article about Nestle's interest in our local water isn't my usual entry, but after noticing that the moderate sized tanker truck I was following down Route 2 in Massachusetts, was carrying none other than "Water," my stomach turned as a I imagined a future of similar "Water" trucks, removing water from one town, selling it to another, all for corporate profit.

So, I am posting this, with hopes that it will encourage citizens around the country to keep close tabs on their own water - before it's sold off - and to consider getting their drinking water (whenever possible) the "old fashioned way" - from the tap.

(Reprinted from The Montague Reporter)

This week, Nestle Water North America announced it was suspending its plan to explore the aquifir below the Montague Plains as the source for a potential water bottling plant in our community. So it seems Montague residents won’t be paying $2 a bottle to purchase our own pure Montague Plains water, at least not from Nestle, and at least not in the near future.

But that’s no reason to let down our guard. That was the message from Tuesday evening’s meeting held by the Montague Alliance to Protect our Water. Following a detailed “tour” of water flow in the plains, and the aquifer below, hydrogeologist Nancy Caffall (formerly with the state Department of Environmental Protection,) noted that “this kind of formation is particularly attractive for bottling companies.”

That’s one reason to keep on guard. Although Nestle’s may have found drilling on State land too “complicated,” because of the nature of the aquifer, and the profitability of a good water source, there’s always the potential for Nestle or another corporate bottler to pursue access through private land abutting the state owned plains.

“A municipal official from the town of Montague should ask if Nestle is talking to other property owners in the area,” suggested Russ Cohen, of the Department.of Fish and Game Riverways Program, prompting discussion of how best to inform nearby property owners of the larger impact, and potential risks of opening the door to a Nestle representative.

What would it take to discourage or deny drilling permits in the state of Massachusetts? In addition various MA DEP regulations, says Nancy Caffall, there is also the Massachusetts Water Management Act which requires that water withdrawals not stress the host river basin. That is, all withdrawals to a particular basin are considered rather than a more piecemeal approach, or one that considers only the impact on nearby surface waters.

Ironically, what makes spring water Spring Water is that it must be withdrawn from a location that is hydrogeologically connected to a surface stream. In other words, sites that are often more ecologically sensitive – with nearby habitat, freshwater fish streams etc.

And, says Kirt Mayland, Director of the New England Office of the Eastern Water Project of Trout Unlimited, the water industry wants to keep it this way – rather than going to sites where there’d be less impact. For example in Wisconsin, bottlers have drilled wells near some of the best trout streams in the region.

The case of Montague verses Nestles didn’t get as far as evaluation of impacts on nearby streams, or host river basins, in part thanks to the now famous Article 97. In addition to guaranteeing the people’s right to public resources, Article 97 also grants that removal of natural resources from public lands must be in the best interest for wildlife and wildlife habitat. So, unless like us, critters living on the plains have turned to bottled water, it’s hard to envision how corporate withdrawal would be of benefit to them, or to the public.

But as one meeting participant pointed out, “While Article 97 seemed like a real silver bullet, and although it has the most wonderful language for resource protection, there are a lot of terrible plans that happen – in this case the state may have been sensitive to all the opposition because it’s on state land.” Since most legislation regulating and protecting water was passed in the old days, when we drank water from the kitchen sink, or the bubbler down the hall, and before the rise of the multi-billion dollar bottled water industry, there are plenty of loopholes that corporations with deep pockets can ferret out. In short, there’s plenty of work to be done identifying and filling in the loopholes of state water legislation.

Not only is the extraction of a common trust resource, one that should be as free and accessible as the air we breath an issue, but between the trucking and the bottling there are plenty of other environmental impacts of the bottled water industry.

“There’s a whole lot of trucking,” impressed Mayland who noted that because the industry is so reliant on trucking, and because fuel prices are soaring, and because we here in the Northeast are major consumers of bottled water, the Route 91 corridor is of particular interest to bottled water developers, as are other locations in the Northeast that combine access to good water with access to good roads.

There is no doubt we have, in part, brought this upon ourselves by becoming a culture reliant upon bottled water. According to the group Corporate Accountability International “One of the most visible examples of corporate control of water is bottled water. It is the fastest growing sector of the US beverage market and just three corporations – Coke, Pepsi and NestlĂ© – make up over half of the US bottled water market. These corporations are privatizing our water, bottling it and selling it back to us at prices hundreds, even thousands of times what tap water costs. They have turned a shared common resource into a $100 billion global market – and one of the world’s fastest growing branded beverages.”

But if corporate greed isn’t enough to make you think twice about purchasing that next bottle of Aquafina, Poland Springs, or Evian, then think locally. We all know what happens to bottles that aren’t recycled, they’re tossed into garbage, flattened along the road side, or floating down the river. Then there is the toxic side of plastic bottles, and the potential for bottles, depending on the plastic to leach small amounts of toxicants into drinking water.

It’s time to turn back to the tap, relinquishing the bottle, and protect our municipal waters.