#cheese...

HUANS SMELL AND WANT TO DISECT ZIM

A number of other MAOIs followed iproniazid onto the market, of which the best known were phenelzine and tranylcypromine. In 1961 there was a report in the Lancet of a patient who had a fatal subarachnoid hemorrhage while taking tranylcypromine. Subarachnoid hemorrhages are uncommon but occur frequently enough to make it al but impossible on the basis of a single case to implicate a drug that someone might have been taking. Reporting such a case in a journal like the Lancet, however, indicates a certain degree of suspicion on the part of the clinicians involved. This was one of seven such cases reported between 1961 and 1963. Some were fatal, but in those instances the subjects were taking more than one drug, making it impossible to finger tranylcypromine.

It also seemed that primary care physicians were noticing an increased occurrence of headaches in patients taking MAOIs. Examination of such patients suggested that some had blood pressure elevations, which could potentially tie in with the subarachnoid hemorrhages. Barry Blackwell, a psychiatric trainee at the Maudsley, drew attention to the possibility in a letter to the Lancet, which caught the eye of a hospital pharmacist in Nottingham named Rowe. He wrote to Blackwell detailing the occurrence of headache and hypertension in his wife, who had been taking a MOAI, after she ate cheese. Could there be something in cheese which cause a problem for people on these drugs? Blackwell and his colleagues were amused at the suggestion and dismissed it, not knowing that some of the American clinical trialists for tranylcypromine had noted headaches as a side effect. Max Lurie even suspected an interaction with the food that people were eating.

Gerald Samuel, working with one of the manfuacturers of an MAOI at the time, was less skeptical than the Maudsley doctors because the company had received two other suggestions of a similar nature. His remarks encouraged Blackwell and a colleague to take tranylcypromine for a week and then have cheese--nothing happened. The notion might have died at that point but that weekend Blackwell was called to see a lady who had taken phenelzine and had developed headache and hypertension--after a cheese sandwich. A patient in the hospital taking tranylcypromine agreed to take cheese with lunch and several hours later developed the increasingly familiar symptoms, as did two other patients in the hospital the afternoon after cheese made its weekly appearance on the dinner menu.

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The medical profession only began to take the observations seriously when a scientific account could be given for what was happening. Ultimate it was shown that cheese contained tyramine, which appeared in the bloodstream after it was eaten. This could indeed increase blood pressure. The implicated was that the inhibit of monoamine oxidase in the wall of the guy allowed more tyramine than usual to enter the blood stream and hence the problem. The "cheese effect" was born. A variety of other foods were then shown to be problematic as well, including both wine and beer, beans, and other vegetables.