Pick Your Poison

I have a confession to make.  For years now I’ve been guilty of poisoning my patients.  Not the “Arsenic and Old Lace” type of poisoning, or the Dr. Kevorkian variety that shepherds patients into the next life, but poisoning none the less.

No, the kind of poison I provide is both legal and even encouraged in this age of modern medicine.  You could go so far as to say that I would be unable to ply my trade without the particular type of toxins I promote.

Now, before you report me to the state authorities you need to understand the basic gist of my message: most of the medications we prescribe are actually designed to poison some natural physiological process in order to achieve a therapeutic goal.

To understand where I’m going with this you need to imagine for a moment that you are a member of an early society of hunter-gatherers foraging off the land and enjoying an occasional mastodon barbecue.  Your life expectancy would be no more than about 40 years and your demise would come at the claws of some oversized carnivore or as the victim of a microscopic pathogen.  Lack of optimal nutrition and vitamins would stunt your growth and leave you susceptible to a myriad of illnesses that in today’s world would be easily treatable.

It was in this environment that our bodies developed (I use this term in an attempt to avoid offending the third of my readership that holds to evolution, the third that believes in creation, the third that favors intelligent design, and the third that maintains our ancestors were deposited on earth by passing UFOs—as well as those who have trouble adding fractions).  We were never really constructed to live as long as we do now, and our ability to outlive these common modes of death (infection, predators, trauma) and stick around long enough to die of cancer and heart disease is a relatively recent phenomenon.

As such, our bodies have highly developed mechanisms in place to deal with the physiological repercussions of being attacked by a saber-toothed tiger, winnowing away from starvation, and succumbing to tularemia or Staph aureus.  For example, if your body senses a drop in blood volume it assumes that you are bleeding to death and triggers a series of responses designed to maintain adequate perfusion to the brain and other vital organs (sodium retention, vascular constriction, increased adrenalin and cortisol).  To protect you from starvation when nutrition is scarce your fat cells horde adipose (an excellent source of concentrated calories) during times of plenty.  Such adaptations kept our distant ancestors alive amid the trying circumstances of their meager existence.

Now return to the 21st century.  If you look at the mechanism of action of most of the drugs we use you’ll realize that they help you by interfering with processes that your body thinks are perfectly appropriate.  Take aspirin, for example, which works by blocking the production of thromboxane, a molecule that serves as glue and holds platelet cells together in blood clots.  If you’ve just been gored by a megaloceros you can count thromboxane as your best friend as it seals up the wound and keeps you from exsanguinating.  If, however, your wound is nothing more than a tiny tear in the inner lining of a cardiac blood vessel, sticky platelet cells become your mortal enemy as they congregate in your coronaries and cause a heart attack.  Aspirin effectively poisons thromboxane production for the life of the platelet cell.

The body’s adaptation to conserve fluid is a healthy reaction in a bleeding cave-dweller or a parched bedouin, but it’s exactly this response that triggers uncontrollable swelling and life-threatening shortness of breath in patients with congestive heart failure.  Finely tuned feed-back receptors in the carotid arteries and kidneys sense a weak cardiac pulse and low blood pressure and mistake these as signs of dehydration or blood loss.  To counteract this, the body releases hormones that conserve fluid, raise blood pressure, and rev up the heart.  Over time these reflexive measures further weaken the heart and kidneys and are every bit as deadly as an entelodon with a grudge.  We block these responses by poisoning the nephrons of the kidney (with diuretics like furosemide), sabotaging the enzymes that produce vasoconstricting substances (with ACE-inhibitors and ARBs), and barricading the receptors on the heart that bind adrenalin.

The concept of using poisons in the therapy of physical maladies is not new.  For many decades the only treatment for syphilis consisted of ingestion of mercury (a highly toxic heavy metal) or early arsenic-based antibiotics.  Prior to the development of penicillin, the glittery yet deadly metal silver used to be a mainstay in the treatment of gonorrhea.  To this day we still rely heavily on compounds that, in higher doses, can be used as potent poisoning agents (see previous posts on warfarin and digitalis).  The Botox favored by aging and sagging celebrities is nothing more than botulinum toxin—one of the most potent of all biological poisons—and many anesthesia drugs are based on the same curare found on the tips of arrows in South America.

The drugs that fall into the broad category of cancer chemotherapy are perhaps the most blatant of all therapeutic poisons.  In order to treat malignancy you need to have a medication that kills cancer cells but doesn’t harm non-cancerous ones.  The only problem is that cancer cells are so similar to native cells that it’s next to impossible to tease out a difference that you can exploit.  One thing that does separate cancerous from normal cells is the rate of growth—by nature, malignant cells are constantly dividing (this rapid growth is what makes cancer problematic).  If you can find a chemical that targets rapidly-dividing cells you’ve got your therapy.  This is in essence how many chemotherapy drugs work.  The problem is that malignant cells aren’t the only ones in the body with a rapid rate of turnover—hair follicles and cells that line the gastrointestinal tract are often unintended victims of “friendly fire” and as such produce the loss of hair and bowel side effects that we associate with chemotherapy.

In fairness, there are many drugs on the market that don’t fall into the category of therapeutic poisons.  Some medications serve as replacements for physiological substances gone missing, e.g. thyroid hormone replacement and insulin.  The entire class of antimicrobial drugs (antibiotics and the like) is poisonous, just not to humans.  These drugs exploit the numerous differences between human cells and bacteria and are able to kill the bugs without harming the host.  Penicillin weakens bacterial cell walls, the fluoroquinolones (such as Levaquin) disrupt bacterial DNA, and drugs like erythromycin do stuff I don’t even really understand (they bind rRNA subunits and mess with aminoacyl translocation, whatever that is).

The human body is a bit like a teenager with a set of car keys—sometimes we have to sabotage its activity in order to protect it from itself.  The older you get, the more your body reacts in ways that are not conducive to life in the golden years.  We no longer live in the age of saber-toothed tigers and famines.  Our new adversaries are vascular decrepitude, unchecked malignant cell growth, and a few dozen other common maladies for which the body’s own systems are at least partially to blame, and for these problems we’ve developed a cornucopia of poisons that will buy us a few extra years and a few more miles.

We as doctors just need to keep the whole poison paradigm in mind.  Fancy packaging and slick advertising of modern medicines aside, we’re still applying the same principles that our forebears did when they used mercury, arsenic, and silver to root out disease; the only difference is that our pills and potions are more refined and scientifically tested.

In the end I suppose I’m guilty as charged when it comes to the peddling of poisonous nostrums.  In my defense I do try to remember the age-old exhortation of Hippocrates to “first, do no harm” (primum non nocere) and weigh the benefit of my intended therapy against the very real danger of sabotaging a normal (yet perhaps unhealthy) bodily process.