All drugs are poisons, and that’s OK

There are a number of aphorisms that one imbibes over many years of medical education, especially in medical school. Some are useful; some are not; but some stick with you for reasons that even you can’t figure out. For example, I still remember my first day of medical school over 30 (!) years ago. It started with an introductory session beginning at 8 AM that lasted about an hour, an “orientation,” if you will, after which classes began as normal. During this orientation, members of the medical school leadership, such as deans and the chairs of certain major departments, got a chance to speak to the brand new medical students, introduce themselves, and impart a little wisdom, such as they saw it. Not surprisingly, there was the usual “rah rah” about how lucky we were to be attending the University of Michigan Medical School, how we were the elite, the 170 or so students accepted out of over 3,000 applicants, the usual blather. I imagine that it’s the same sort of thing they do now in “white coat ceremonies,” but back then there was no real ceremony, and, as far as I’m concerned, it was good that there wasn’t. I personally find white coat ceremonies that nearly every medical school now indulges in when a new class enters the school to be just a little too reminiscent of rituals welcoming new initiates into a religion for my liking.

Be that as it may, one thing I remember from the thankfully nonexistent pomp and circumstance I experienced starting medical school. The first was one of the professors (I forget which one) telling us that, ten years after we graduated, we will have forgotten at least 75% of what we learned, but what we remembered would be the “right” 25% for our patients. He also told us that at 50% of what we learned would be out of date; so we would have to learn to learn.

Another aphorism that I distinctly remember from later in my medical school experience was delivered on the very first day of my pharmacology class. Within the first five minutes the professor told us that all medications were poisons. They all interfere with normal cellular processes in some way. The ones we use as physicians just interfere with cellular processes in a way that can be beneficial in disease, and, quoting Paracelsus, he noted that the dose makes the poison.

So, yes, all medications are poisons in that they “poison” an enzyme or other biomolecule. (Look for a quack near you to quote mine that statement by saying, for instance, “Orac says all medications are poisons” and leaving out the rest of the sentence.) I’ll give you an example: Aspirin. Aspirin, as many of you know, is acetylsalicylic acid. This particular molecule irreversibly inhibits an enzyme called cyclooxygenase (COX), which is involved in the production of mediators of inflammation, among other things. The exact details aren’t important, such as how aspirin inhibits the COX1 version more than COX 2 or how it does so by attaching an acetyl chemical group to the active site of the enzyme. The point is that aspirin permanently inactivates an enzyme. It poisons the cell. That’s how it works. In fact, when used as a “blood thinner,” aspirin permanently poisons a certain kind of cell, namely the platelet. Because a platelet doesn’t have a nucleus, it can’t make more COX. What it has when it’s made is all that it will ever have, and if that COX is irreversibly blocked, that platelet’s function is impaired for the rest of its lifespan. Again, without getting too technical, that’s how aspirin works as a blood thinner. It’s an antiplatelet drug.

Speaking of blood thinners, I couldn’t help but think of that medical school aphorism from pharmacology class as I read a particularly brain dead article published on the website of that über-crank and quack, Mike Adams, entitled POISON PRESCRIPTION: Warfarin rat poison widely used as prescription blood thinner. (Alternate Google cache link, given that Adams seems to have some sort of weird redirect thing going on.) Oddly enough, given the inflammatory language in this article and the general level of neuron-numbing medical ignorance on display, the article actually wasn’t written by Mike Adams himself. Rather, its author by someone named S. Johnson, who is apparently too embarrassed to use his or her first name:

Many drugs pushed out by Big Pharma are equivalent to rat poison, but only a handful can actually claim to be rat poison. Meet warfarin: a widely used blood thinner which, prior to being used to treat a common heart rhythm disorder called atrial fibrillation, was used as rat poison.

This is, of course, true. Warfarin and related chemicals have been used as rat poison. However, warfarin is also used as a useful drug. Thee is no inherent conflict in this concept, nor is “big pharma” trying to poison us like rats by using warfarin. Indeed, there is only a conflict between these two uses if you buy into the idea that anything pharmaceutical is evil and anything “natural” must be good and utterly forget the concept of the dose making the poison. Something that in small doses can have a useful therapeutic effect can be toxic in large doses. In small doses, warfarin inhibits coagulation by interfering with one set of proteins that promote coagulation. In high doses, not surprisingly, it causes massive bleeding. The former is useful in preventing thrombosis-related complications of various diseases, like atrial fibrillation. The latter is useful because rats will eat warfarin up until they start bleeding.

Johnson goes on:

The compound responsible for bleeding – dicumerol – was discovered in 1934. In the early 1940s, it started to be tested in people as a blood thinner. In 1945, a stronger version of dicumerol was patented and named after the Wisconsin Alumni Research Foundation (WARF).

Around that same time, a close cousin of warfarin, named coumafuryl, was marketed as a rat poison under the brand names Rat-A-Way and Lurat. Coumafuryl was considered an effective rat poison for its odorless and tasteless quality, making it easier to feed to rats.

Warfarin was originally too strong to be given to people. However, it was prescribed for medical use in 1954, and increased in popularity in the early 1990s for slashing the risk of annual strokes by two-thirds, from 4.2 percent to 1.4 percent.

Patients prescribed warfarin for atrial fibrillation will likely be dependent on the rat poison for the rest of their lives. Although warfarin is widely prescribed, particularly to the elderly, few patients are aware that they are literally ingesting rat poison. Warfarin is now one of the most widely used oral anticoagulants in the United States.

Yes, it is, and with good reason. It’s inexpensive, and it works. Johnson also neglects ot mention that the reason why warfarin/coumadin could be used in humans was the development of a blood test to measure how much of an anticoagulation effect it was having, which allowed for monitoring and dose adjustment and made its administration much safer.

Of course, coumadin does have a number of downsides, as Johnson notes. It requires monitoring. Bleeding complications are too common. Specific foods, particularly any food rich in vitamin K, can interfere with its effects. I know as well as anyone how tricky coumadin can be. During, any time I was on a vascular surgery rotation I’d be faced with trying to monitor and titrate patients’ coumadin doses based on their blood tests. Indeed, back then, before the development of better anticoagulant drugs, it was often my job to switch patients over from intravenous heparin to oral coumadin, and patients couldn’t go home until their blood values were within a therapeutic range. I know as well as anyone else that coumadin is a problematic drug, and physicians have always known it’s a problematic drug. so much of what Johnson writes is not anything any physician who prescribes coumadin doesn’t already know.

Next, Johnson points out that there are downsides to coumadin:

In particular, the researchers found that the rate of interracial hemorrhages associated with the use of blood thinners in the Cincinnati area increased from 0.8 cases per 100,000 people in 1998, to 4.4 cases per 100,000 people in 1999. For people 80 years of age and older, the rate jumped from 2.5 in 1998, to a shocking 45.9 in 1999.

“For many people, the benefits of preventing ischemic stroke continue to outweigh the risk of a hemorrhagic stroke. Our findings should not discourage the use of warfarin when it’s appropriate. Doctors can use these findings to make sure they are weighing the risks and benefits of warfarin use for their patients. For researchers, these results may stimulate efforts to develop safer alternatives to warfarin and better treatments for people with brain hemorrhages,” said lead author and neurologist Dr. Matthew L. Flaherty.

According to Dr. Michael B. Rothberg, a former associate professor at Tufts Medical Center, doctors should consider the risk of stroke versus the risk of bleeding when prescribing warfarin.

I wondered what article Johnson was citing; so I did some PubMed searches. This appears to be the report. Not surprisingly, there appears to be a bit of cherry picking going on here, because this report was from 2007, and a more recent report from 2014, which encompassed a nationwide study in Sweden, found the risk of warfarin-associated intracranial hemorrhage to be low. Still, there’s no denying that warfarin increases the risk of intracranial hemorrhage. How could it not. It “thins” the blood; it decreases the blood’s ability to coagulate. That’s its purpose.

As noted above, whenever a physician treats a disease or condition with a drug—or any other treatment, for that matter—it’s a question of balancing risks with benefits. All real physicians know that. It’s what they are trained to do. It’s only in the fantasy world of deluded idiots like Mike Adams, Joe Mercola, antivaccinationists, and the usual assortment of quacks and cranks that there are medications or treatments for illness that have real therapeutic effects that don’t also have risks and side effects. In some cases, these side effects and risks can be serious. Even when true, that doesn’t invalidate or otherwise render useless the treatment and its therapeutic effects.

Here’s an example I like to give. The treatments for cancer often include a combination of surgery (sometimes radical), chemotherapy (which is definitely very toxic), and radiation (which can be toxic). Given that the cancers for which these treatments are routinely used can kill you, on balance, the use of such “poisonous” treatments can be justified. Yes, they can cause horrible toxicity. But, also yes, they save lives. On balance, the benefits usually outweigh the risks. The science and art of medicine involve determining when the benefits do and don’t outweigh the risks and to proceed accordingly. It sounds straightforward, but it most definitely is not.

Of course, this being and all, there is no such thing as nuance. Demonization of pharmaceuticals is the name of the game. This becomes clear here:

Fortunately, there are alternative blood thinners out there without the dangerous side effects anchored to prescription drugs. Both cayenne peppers and vitamin C, for instance, are great for the blood vessels and heart in general. Other natural blood thinners include foods rich in salivates, a natural chemical that serves as a major ingredient for pain-relieving medications. Sources of salivates include cinnamon, turmeric, peppermint, oranges, raisins, blueberries and honey.

Here’s the problem None of these “alternative blood thinners” can do what warfarin does. If they could, physicians would use them. None of these “alternative blood thinners” can “thin the blood” to anywhere near the degree or with anywhere near the potency as coumadin. Moreover, there are now other drugs designed to have similar effects as coumadin, albeit through different mechanisms, drugs that don’t require the close monitoring that coumadin does. One example is Plavix and related drugs.

So why call warfarin rat poison in such a blaring headline and repeatedly in this article, as Johnson does? Yes, it’s true. You got us! Coumadin/warfarin was (and still is) used as rat poison! You brilliant Mike Adams drones! We evil pharma minions can’t pull one over on you!

So what if coumadin is rat poison?

All drugs are poisons, and that’s OK. They couldn’t work if they weren’t poisons. It’s the nature of the poison—and the dose—that determines their usefulness, and all drugs have risks to go along with their benefits. Damn that nuance.