The nationwide case-cohort study in pharmacoepidemiology: a study of iatrogenic anaphylaxis and agranulocytosis

Drug safety is an important palt of postmarketing surveillance. In ancient times, people were already aware of the fact that drugs could have side effects. The oldest drugs were mainly of plant and animal origin, but also mercury, arsenic and antimony were used, the toxic effects of which were well known. In 1224 Frederick II, Emperor of Hohenstaufen ordered inspection of drugs and mixtures prepared by apothecaries and in 1518 the Royal college of Physicians was founded, whose Fellows were also concemed with quality control of drugs. The first drug to be banned because of its toxicity was antimony in the 17th century. It was used again, however, after it cured Louis XIV from typhoid fever. One of the first descriptions of an intoxication to a drug which is still in use today, was made by William Withering in 1785. He described digitalis intoxication as follows: "The Foxglove, when given in very large and quickly repeated doses, occasions sickness, vomiting, purging, giddiness, confused vision, objects appearing green or yellow, increased secretion of urine with frequent motions to patt with it, and sometimes inability to retain it; slow pulse, even as low as 35 in a minute, cold sweats, convulsions, syncope and death".

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