Monday, June 8, 2015

Digitalis - or putting my toddler into heartblock

My family and I have recently moved to a different part of the country and while I wait for the paperwork to go through to start a new job I am getting on with planting a garden in our new home.  I came home with seeds - pansies, sunflowers, violets and foxglove all of which looked very pretty on the packet and was planting them while my toddler enthusiastically "helped" (as toddlers do).

It wasn't until I was about ready to plant and looking at the packet for a second time that a bell started ringing in my head.  I turned it over and sure enough, there in very small print was the warning that foxglove was poisonous if ingested.  With the small tornado enthusiastically eating grass beside me, the seeds were quickly disposed of in the bin.

So what is foxglove, apart from quite pretty?

(public domain image sourced from wikipedia)

Foxgloves or digitalis which is its latin name are a family of around 20 different flowers found in Europe, west Asia and northern Africa.

Foxglove had clearly been used by herbalists for a long time.  It appears to have been unknown to Greek and Roman physician but was widely used in Europe from the middle ages onward for a variety of conditions, it seems mainly chronic coughs and the invariably fatal 'dropsy'.  Dropsy was the name used for the accumulation of excess fluid throughout the body. Today we know that to generally be a sign that the heart is failing to work properly.

Digitalis is now known as digoxin and has been used throughout much of the 20th century to treat, 'dropsy' - a term used to encompass both heart failure and atrial fibrillation(an abnormal heart rhythm) in the modern clinical setting.  In other words, this was a herbal remedy that actually worked.  So it's interesting that it's use was not noted or quantified by the mainstream medical profession until late 18th century.  This work was done by a doctor named William Withering.

Withering was born in 1741 in Shropshire to a prosperous apothecary.  He graduated with a medical degree from the University of Edinburgh in 1766.  Withering started as a general practitioner in Staffordshire and then in 1775 moved to Birmingham (on the advice of friend Erasmus Darwin - grandfather of Charles Darwin).  His practice in Birmingham was wildly successful and he became a physician of national fame.



Not only a physician, also a keen scientist, Withering was passionate about medicine, minerology and botany publishing papers in all three fields. Despite many scientific accomplishments - he is best remembered for the 10 year clinical trial that brought digitalis to modern medicine.

"In the year 1775 my opinion was asked concerning a family receipt for the cure of the dropsy. I was told that it had long been kept a secret by an old woman in Shropshire, who had sometimes made cures after the more regular practitioners had failed. I was informed also, that the effects produced were violent vomiting and purging; for the diuretic effects seemed to have been overlooked. This medicine was composed of twenty or more different herbs; but it was not very difficult for one conversant in these subjects, to perceive, that the active herb could be no other than the Foxglove"

These are the famous opening lines from Withering's book An account of foxglove and some of its medical uses, first publised in 1785.

Interestingly - this is one also one of the first noted cases of academic plagarism.  The previously mentioned Erasmus Darwin also published on foxglove five years earlier - from work clearly stolen from Withering.

Withering quantified that digitalis could both slow the heart and induce a diuresis (reduction in fluid). He also noted its effects in overdose - nausea, vomiting, diarrhoea, yellowed vision, abnormal heart rates, seizures and death. He noted that although herbalists used it for cough - it had no effect. As his research continued his book shows fewer adverse outcomes as his understanding of dose increased.

Withering's book was a landmark in medical research as it not only showed a new treatment for dropsy but described the importance of acheiving consistency of dose, dose response relationship and adverse events.  This is, in effect, an early effort in an area now known as clinical pharmacology.


Although digoxin is now losing popularity as a treatment for heart failure and atrial fibrillation in favour of newer pharmaceuticals, I'm the 1700s it was the only known treatment.  And it worked.  Suddenly dropsy was no longer fatal.  With such a narrow therapeutic window Withering's research proved invaluable and the lives of many patients were better for it.

In 1783 Withering diagnosed himself with pulmonary tuberculosis.  He attempted to treat this with several trips to warmer climes in Portugal but eventually succumbed in 1799. A memorial stone in a Birmingham church is surrounded by carved foxglove in his honour.


https://books.google.com.au/books?id=VgIta49rzT4C&pg=PR3&hl=en#v=onepage&q&f=false
http://www.historyofscience.com/articles/jmnorman-william-withering.php
http://www.clinmed.rcpjournal.org/content/6/4/393.long
http://www.onlinejcf.com/article/S1071-9164%2809%2900956-7/pdf



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