Monday, December 29, 2008

An Unexpected Cure- Anabuse

Jack Dini

(From a series on Unintended Consequences)


Scabies is an itchy condition of the skin caused by tiny mites. The severe scratching brought on by this infection can often trigger infections, which leave scars. Scabies was endemic during World War II in Europe. Swedish researchers discovered that it could be treated by using disulfiram (tetryethylthiuram disulfide), a chemical that had been used in the rubber industry), as an ointment. (1)

In Denmark, Drs. Jens Hald and Erik Jacobsen, were interested in finding a pill that would be effective against intestinal worms. They had reasons to believe that disulfiram might be the solution so decided to run some tests. They first experimented with rabbits. As far as they could tell, rabbits infected with the internal parasite and then fed disulfiram pills showed no adverse reactions and the drug seemed to work.

What to do next? They undertook what is a taboo in medical research—self -experimentation. Lawrence Altman, in his fascinating book on this topic Who Goes First?, says this about Jacobsen, “He lived by a strong moral code. In his work, he believed that pharmacologists should test a drug on themselves before doing so on another human. He practiced what he preached.” (1)

So Jacobsen and Hald began taking disulfiram pills on a daily basis in their different laboratories. Shortly after the experiment began. Jacobsen decided to have a bottle of beer with the sandwich his wife had made for him. By the time lunch was over, Jacobsen felt groggy and nauseated, and his head throbbed. The next day he ate another sandwich and was fine. Then he had lunch with his managing director. During this event they had consumed a glass of aquavit in a friendly gesture of comradery. Once again, the symptoms re-appeared, but then after a while were gone. So he went on about his business. (1)

Later that same week, Jacobsen had a beer with a meatball sandwich his wife had made. Again he had another attack so went home early. He wanted to blame the meatball sandwich but found that the rest of his family had eaten similar sandwiches with no ill effects. The attacks continued but Jacobsen shrugged them off until he met Hald in the corridor at work one day. As Jacobsen related his observations and problems with nausea, etc., Hald said, “That’s funny. I have had the same bug.” (1)

Hald told of a recent visit of one of his friends where they shared some cognac. Hald had become sick and the friend had not. These shared experiences got them both to wondering if there could be some relation between disulfiram and alcohol. They decided to do more tests; avoid both the drug and alcohol, drink alcohol but avoid the drug, take the drug but avoid alcohol, and lastly, have alcohol while on the drug. Bingo! Both had the symptoms return when mixing the drug with alcohol.

Then they repeated the experiment on a fellow laboratory worker. After a few days the same result was obtained. It did appear that for some reason the body needed a few days to trigger the disulfiram-alcohol reaction. As a final test, Jacobsen took some pills before injecting himself with a small amount of alcohol. His blood pressure fell almost to zero and he nearly died. There was no longer any question about a reaction between alcohol and disulfiram. Soon after this, a chemist friend identified the odor on Jacobsen’s breath as acetaldehyde, a toxic product of oxidation of alcohol. (1)

As far a Jacobsen and Hald were concerned there went the grand scheme for the proposed cure for intestinal parasites, and since they felt alcoholism wasn’t an important medical problem in Denmark, they saw no reason to continue with this project. That is, until Jacobsen attended a civic affairs meeting in October 1947. He was asked to fill in for a speaker who cancelled at the last minute and during the course of his talk he mentioned the experiences he and Hald had with disulfiram and how as a result of this neither could stand alcohol while on the pills. John Emsley reports, “A journalist from the Copenhagen newspaper Berlingskee Tidende was present, and reported the story. Alcoholics who read about disulfiram realized that here was a treatment that might wean them off alcohol, and several of them wrote to Jacobsen, asking for disulfiram tablets. Clinical tests on alcoholic volunteers showed that the drug could be used to break the addiction to alcohol. Antabuse, the trade name Jacobsen gave the drug was launched.” (2)

So how does disulfiram (Antabuse) work? It blocks the enzyme that converts acetaldehyde to acetic acid and as the body builds up acetaldehyde, it produces a condition know as acetaldehydemia. This usually results in a very unpleasant reaction. Again from Emsley, “Even a little alcohol taken by someone on Antabuse produces enough acetaldehyde for their body to react unpleasantly to it. They feel very ill because they are in effect experiencing a severe hangover, the symptoms of which are nausea, vomiting, labored breathing, flushing, chest pains, and throbbing headache. The experience is so dreadful that they will usually avoid alcohol while they remain on Antabuse, although it has been found that some people become tolerant of the drug and its effect is diminished. Most people who take Antabuse find it effective, but they must also be alert to the fact that some common household products contain alcohol, such as vanilla extract (35% alcohol), cough medicines (up to 25% alcohol), and mouth washes (around 25% alcohol.)” (2)

Walter Gratzer rightly notes that this is an example of a heroic experiment conducted by doctors on themselves that could never have come about by design. (3) One- they weren’t even looking for a treatment for alcoholism, two- if they hadn’t experimented on themselves they would never have known of the consequences of mixing alcohol with the drug, and 3- if Jacobsen hadn’t been asked to be a substitute speaker at a civic meeting, the results would probably been buried in laboratory notebooks and never revealed to the public.

A final word of caution. Mixing Antabuse and alcohol can be deadly. Joe and Teresa Graedon highlight the fact that ‘in some cases, the reaction could be lethal, so anyone on Antabuse really needs to watch out for alcohol.” (4)




References

1.Lawrence K. Altman, Who Goes First?, (New York, Random House, 1987), 98-104

2.John Emsley and Peter Fell, Was it something you ate?, (Oxford, Oxford University Press, 2001), 28

3.Walter Gratzer, Eurekas and Euphorias, (Oxford, Oxford University Press, 2002), 163

4.Joe Graedon and Teresa Graedon, Deadly Drug Interactions, (New York, St. Martin’s Griffin, 1997), 146

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