Tuesday, February 19, 2008

Weeds, Sick Cows, a Failed Suicide, and Your Grandmother's Heart Medicine

Sweet clover grows as a weed thoughout many areas of the United States, particularly the Great Plains. It is not a native species, having been introduced to this continent by 17th-century European settlers. It's used in animal feed, but otherwise it's considered to be a nuisance by many people.

Except, interestingly, for people who have heart rhythms like this:

Something goes wrong with the pacer node of the heart and instead of sending out a regular pulse it sends rapid and erratic signals, some of which sneak through to the ventricles which can then contract and perfuse the tissues of the body. A lot of people are walking around with this. A couple million. And there are about 160,000 new diagnoses made here every year.

People with atrial fibrillation are at greater risk for stroke and pulmonary embolism because blood can "pool" in the fibrillating upper chambers of the heart; allowing clots to form. These can be ejected from the heart, clogging arteries and stopping blood flow to areas of the brain or lungs.

This risk can be reduced by administering drugs that interfere with clotting mechanisms.

I don't think a work day goes by in which I do not administer Coumadin (also called Warfarin or Jantoven) to somebody or other. Hospitals often treat people with new-onset or rapid-ventricular-rate atrial fibrillation, so we do coumadin teaching and get people anti-coagulated on other drugs until the coumadin reaches a therapeutic level in their bloodstream. Sometimes the heart can be shocked back into regular rhythm by elective cardioversion.

That's not the interesting part, though. This is:

"The development of the anticoagulant warfarin is a good example of scientific exploration leading to development of a poison and, eventually, to the serendipitous discovery of a therapeutic agent. In 1922, a hemorrhagic disease was noted in cattle in the Northern Plains of the United States and in Canada. The chief diet of these cattle was silaged sweet clover, a crop that had been introduced to the Plains in the early 1900s.

In 1939, scientists Campbell and Link identified bishydroxycoumarin (dicoumarol), produced by the fungus Aspergillis, as the toxic agent in sweet clover. Bishydroxycoumarin produced anticoagulation by its antagonism of vitamin K. The anticoagulant properties of this substance were exploited by K.P. Link in 1948 in the development of "warfarin," a potent rat poison. In 1951, a military recruit survived a suicide attempt using warfarin, and researchers perceived that the agent, if properly titrated, could be used therapeutically as an anticoagulant."

From Poisons to Therapeutics: The Historical Origins of Contemporary Pharmacology,
Susan Russell Neary, PhD, ARNP-BC


wunelle said...


My mother was on Coumadin for this condition, and had a severe stroke when the medicine was temporarily withdrawn in preparation for a colonoscopy. She had worked herself onto a very narrow ledge, and the short time without the anticoagulant caused a clot to form and be sent out, just as you describe.

A non-medical person like myself hasn't the foggiest idea of how these drugs come to be. So this is an interesting story with an oblique connection.

Amy said...

Thank goodness for Coumadin! I was diagnosed with atrial fib. when I was 22, and have had multiple ablation and cardioversion procedures without success. Trials of 2 different antiarrythmics (flecainide and sotalol) have both resulted in the development of sustained and unstable V-tach (fortunately, both incidents happened in the hospital while I was being monitored), so Coumadin is the only thing keeping my brain and lungs safe. I knew that warfarin was used as rat poison, but I didn't know about the rest of the info. in your post.

Nurse Practitioners Save Lives said...

I guess it's true about what won't kill you, may cure you... Coumadin is a scary med to keep in control at times. It definitely does the job though.