Accidental Blockbusters: Viagra

“What is luck', he said, 'but the ability to exploit accidents?” Jeanette Winterson

Viagra is a well-known name. It is used to treat over 90 % of patients with erectile dysfunction but in fact was developed for an entirely different condition.

Viagra was originally developed in Kent as a treatment for hypertension. Phase 1 trials in patients in Swansea showed that whilst it had little effect on angina, it did induce marked penile erections. And so Pfizer decided to market it for erectile dysfunction rather than hypertension.

The drug inhibits an enzyme leading to dilation of the veins increasing blood flow in certain areas. In the penis, this causes an erection. However Viagra is also used in an area linked more towards its original research field; pulmonary arterial hypertension. In this condition patients suffer from constricted blood vessels causing shortness of breath, as oxygenated blood cannot reach the heart. Viagra is used as one of the treatments for this condition to help relax the blood vessels allowing efficient blood flow to the heart.

 

Viagra, interestingly, has been documented as a drug of abuse in sports, as athletes believe that opening up blood vessels will enrich their muscles with oxygen, an especially useful feature in endurance events. In fact it has already been a point of controversy when the Italian cyclist, Andrea Moleta, was found with 82 Viagra pills on the Tour of Italy, hidden in toothpaste bottles. This bizarre incidence, seeing as doping on Viagra would be very unsubtle in such tight lycra, led to confusion at the time. Although no doping allegations could be made, seeing as Viagra is yet a banned drug, he was nonetheless excluded from the tour on suspicions of attempting to bypass blood doping tests.

The World Anti-Doping Agency (WADA) is currently investigating whether to ban Viagra in sport, by testing in possibly the least likely bunch of people to need the drug; collegiate athletes. Lacrosse players at Marywood University are taking part in a study to look at whether an increased blood-flow, and hence oxygen capacity, can really benefit athletes. If this is found to be the case, it will be added to WADA’s extensive list of banned substances.

 

Accidental Blockbusters: Disulfiram

 

“Men occasionally stumble over the truth, but most of them pick themselves up and hurry off as if nothing had happened.” Winston Churchill

Disulfiram is a drug used to support the treatment of chronic alcoholism. It came about after a strange occurrence in the 1920’s; men working in a rubber factory suddenly found that when hitting the pub after work, they had lost their tolerance to alcohol. This was largely ignored at the time until 20 years later Dr Erik Jacobsen investigated the use of disulfiram to treat intestinal worms. He ingested some of the drug before attending a dinner party, where he proceeded to become violently sick. This led to the connection between disulfiram and alcohol intolerance which further explained why the workers in rubber factories faced similar effects, as disulfiram is a product of chemicals used in their factory.

When you drink alcohol, it is normally degraded by the body into a substance called acetaldehyde. When you drink too much, acetaldehyde builds up in the body and this is what causes you to have a stonking hangover. An enzyme called alcohol dehydrogenase clears acetaldehyde out of the body but not necessarily as rapidly as you drink.

Disulfiram blocks this enzyme meaning that if you even have a sip of alcohol, you will immediately feel the same effects as if you had had a 3 day bender.

Disulfiram is sold in tablets where the effects last less than a week. However in Russia, where there is a long, destructive history with alcohol, you can have a procedure where a Disulfiram capsule is implanted into your buttocks and remains there for three years. In Moscow alone there are dozens of clinics where you can get this procedure done. In fact up to 80 % of alcohol addiction treatments in Russia are from this capsule procedure. Drinking alcohol with this tablet implanted in you is thought by Russians ‘to kill you’. Of course this would in fact be entirely unethical, but the symptoms may suggest as such to the patient. An antidote for these effects can be bought for $300 which renders the drinker back to full health.

Something Wicked This Way Comes

In the February of 1692, two girls from Salem Village in the young American colonies began to suffer from strange fits that left them screaming, uttering strange sounds, contorting into strange positions, and with violent outbursts. A minister from a nearby town described their illness as “beyond the power of Epileptic Fits or natural disease to effect” and – assuming that only the supernatural could cause this illness - the Salem Village soon began the famous Salem Witch Trials.

Swept up by hysteria, everyone accused their neighbors, friends, and family of witchcraft. The town executed twenty people, nineteen by hanging and one by pressing to death when he failed to plead guilty. Five more of the accused died in prison.  The final trial took place in May 1693 and, with the defendants found not guilty, the case officially ended – at least judicially. The trials never died in the mind of the public, however, and for the decades and centuries that followed it obsessed the public with its plethora of unanswered questions.

The Crucible, by Arthur Miller, is based on the witch trials.

One of the main questions: what caused those girls to act so strangely and spark the craze of paranoia that led to so many deaths? Many theories have been put forward throughout the centuries, mostly based on the assumption that the girls faked their illness either to fuel family rivalries or as a cruel prank.

In 1976, Linnda R. Carporael proposed a new hypothesis: that the girls were suffering from poisoning by ergot-tainted rye. Their symptoms cited in the trials – convulsion, hallucination, crawling sensations in the skin, tingling in the fingers, headaches, vomiting, diarrhea, mania, psychosis, and delirium – match that of ergotism. Moreover, there was an abundance of rye in the area and, during those years, the right weather conditions for ergot to flourish. Although this theory has been subject to some academic debate, it is still one of the most widely accepted reasons behind the seventeenth century hysteria. 

Ergot is a group of fungus whose consumption causes a number of severe pathological syndromes in humans or other animals. As early as 1095, a special hospital was founded to treat the symptoms of ergotism. The condition gained the nickname “St. Anthony’s Fire” for the order of monks who founded the hospital and the burning sensation ergot poisoning causes in the limbs of the contaminated.

The effects of ergot have also been used deliberately in drugs. As Paul L. Schiff Jr. explains:

In 1582 a preparation of ergot that was employed in small doses by midwives to produce strong uterine contractions was described by Adam Lonicer in his Kreuterbuch. The use of ergot as an oxytocic in childbirth became very popular in France, Germany, and the United States. The first use of the drug in official medicine was described by the American physician John Stearns in 1808, when he reported on the uterine contractile actions of a preparation of ergot obtained from blackened granary rye as a remedy for “quickening childbirth.” However, shortly thereafter the number of stillborn neonates rose to a point that the Medical Society of New York initiated an investigation. As a result of this enquiry, it was recommended in 1824 that ergot only be used in the control of postpartum hemorrhage. Ergot was introduced into the first edition of the United States Pharmacopeia in 1820 and into the London Pharmacopeia in 1836.

In modern pharmaceuticals, ergot is used in medicines in the form of ergotamine. One example is Cafergot, a Novartis drug which is used to treat migraine headaches. Although cases are rare, the Novartis Consumer Information cites a risk of developing ergotism associated with the drug. Cafergot was discontinued in the UK in 2012. Ergoline alkaloids, originally isolated from ergot fungus, is also used in pharmaceuticals for the treatment of Parkinson’s disease, albeit usually in synthetic derivatives.

It is incredible to consider that we are now able to harness this poison - which has tortured humanity for millennia – for good. Yet the risk of poisoning still remains high, with several outbreaks of ergotism in the twentieth century. The risk of witchcraft accusations may be lower in this day and age, but with Halloween approaching… perhaps it’s best if you watch what you eat.

Sources

Paul L. Schiff, Jr. "Ergot and Its Alkaloids" in the American Journal of Pharmaceutical Education, October 15 2006. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1637017/

“Ergot” from Wikipedia. http://en.wikipedia.org/wiki/Ergot

“Ergotism” from Wikipedia. http://en.wikipedia.org/wiki/Ergotism

“Ergotamine” from Wikipedia. http://en.wikipedia.org/wiki/Ergotamine

“Salem Witch Trials” from Wikipedia. http://en.wikipedia.org/wiki/Salem_witch_trials

"Cafergot” from Drugs.com. http://www.drugs.com/pro/cafergot.html

“Cafergot: Consumer Information” from the Novartis Canadian Website http://www.novartis.ca/products/en/pharmaceuticals-c.shtml

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