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Cherrie Patete
The great advances in medical therapy in the past century have been due largely to the rapid development of chemistry and pharmacology. During this period innumerable compounds obtained in chemical laboratories, were tested for their pharmacological activity. Those proving satisfactory were then produced commercially.
The extent of public acceptance and usage of any one drug has usually been determined by the medical profession. The use of many of the new compounds was only of short duration; they were frequently replaced by other compounds found to be more effective, or which did not provoke inconvenient side reactions.
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The case of "Heroin" (diacetylmorphine) is almost unique. Hailed as a wonder drug, it was received with enthusiasm by the medical profession. Inevitably, the deleterious effects of the drug were discovered. Although many doctors discontinued prescribing heroin and all warned against careless use of the drug, the market for it continued to flourish. A dangerous addiction-producing drug, it was not easy to curtail its usage.
Although diacetylmorphine was not prescribed as a medicine much before 1900 its preparation had already been reported in 1874 by C. R. Wright at St. Mary's Hospital in London.[1] The main purpose of his work was to determine the constitution of some natural and purified alkaloids. By boiling anhydrous morphine alkaloid for several hours with acetic anhydride he was able to isolate acetylated morphine derivatives. The general conception of the morphine molecule in those days was that it was represented by the double empirical formula[2] which gave rise to the rather confusing nomenclature in his article. The extreme acetylated derivative which he obtained, he called " Tetra acetyl morphine." This compound corresponds to diacetylmorphine according to our present nomenclature.
This "Tetra acetyl morphine" was sent to F. M. Pierce, Associate at Owens College, London, for biological assay. After having tested the compound in animal experiments he reported the following results to Wright. The effects were:1"... great prostration, fear, sleepiness speedily following the administration, the eyes being sensitive and pupils dilated, consider able salivation being produced in dogs, and slight tendency to vomiting in some cases, but no actual emesis. Respiration was at first quickened, but subsequently reduced, and the heart's action was diminished and rendered irregular. Marked want of coordinating power over the muscular movements and the loss of power in the pelvis and hind limbs, together with a diminution of temperature in the rectum of about 4, were the most noticeable effects."
From a medical point of view the interest in this new morphine derivative was not very high for the first twenty years. In 1890, a German scientist, W. Dankwortt,[3] prepared diacetylmorphine by heating anhydrous morphine with excess acetylchloride. The result of his work is important, not from the pharmacological, but from the chemical point of view. Because of the nature of the compounds he was able to isolate, he concluded that the morphine molecule had a simple empirical formula rather than the double one.
In the last decade of the 19th century Dreser[4] and other investigators studied the physiological effects of diacetylmorphine. The favourable reports of these investigators along with the growing interest in the drug shown by the medical profession of that time, led the Bayer Company in Eberfeld, Germany, to start production of the compound on a commercial scale (1898).
The new compound was marketed by Bayer under the name "Heroin." (The name is probably derived from "heroisch" which in German medical terminology means large, powerful, extreme, one with pronounced effect even in small doses.) Later this name became a synonym for the drug.
The new remedy received a spontaneous and widespread acceptance comparable to the acceptance of drugs like penicillin or cortisone in the past few years. The high frequency of tuberculosis and other respiratory diseases had created a great demand for an effective remedy and it was hoped that heroin would meet this need.
Prescribed for almost all illnesses in which codeine or morphine had been found, heroin was also considered to be effective in combating addiction to these two drugs. This enthusiasm for the new drug is best illustrated in the medical literature of the time. Though by no means exhaustive, these following excerpts are typical of the writings of the day.
In 1898, Strube[5] reported on the results of studies at the Medical University Clinic of Berlin. Testing heroin on 50 patients afflicted with phthisis, he found it effective in relieving their cough and in producing sleep. Though Strube observed no adverse effects, he felt that further observations were necessary to determine whether continual use might be harmful or lead to chronic "heroinism".
At the request of Dreser, Floret experimented with the drug in the Poliklinik der Farbenfabriken (1898).[6] He found it valuable in the treatment of bronchitis, asthma and tuberculosis. For cases of dry bronchitis where codeine has been ineffective, Floret reported that heroin was unusually prompt and dependable.
These were among the experiments that led to Dreser's[7] endorsement of heroin at the congress of German Naturalists and Physicians in 1898. Claiming that heroin was ten times as effective as codeine in the treatment of respiratory diseases, he estimated that it had only one-tenth of the toxic effects.
H. Leo[8] in reporting the frequent success he had observed in administering the drug, gave a detailed case history of one of his patients. In 1896, the patient, then 71 years of age, developed a severe cough with expectoration and suffered from dyspnea. After being hospitalized in the summer of 1897, and again in the summer of 1898, the patient was finally sent to a sanatorium in November 1898. By this time his condition had become considerably worse. Respiration was rapid and difficult, fat and muscular tissue had deteriorated, the lungs were enlarged and heart action was poor.
"February 4. The patient had been given the first dose the evening before. The night was still without sleep, but the cough was looser and effortless. Also the dyspnea was not so pronounced. After he had taken the drug he felt very comfortable and stated that he no longer felt sick. The action of the heart was somewhat more regular. The appetite was better.
Manges[9] who had previously reported on the advantages of heroin over morphine in the treatment of coughs, phthisis and asthma, reiterated his confidence in the drug in 1900.[10] Reviewing the treatment of the 341 respiratory cases by his colleagues, he stated that addiction was noted in less than eight per cent, without the bad effects accompanying morphine treatment. Where most of the cases included in Manges report did not show habituation, in two cases it had also been found to be successful in breaking addiction to morphine.
Prompted by Harnack's[11] warning in 1899, that heroin might be a dangerous poison, Turnauer[12] tested the drug for the possibility of harmful after effects. After treating 48 cases of phthisis, bronchitis and dyspnea, Turnauer noted a tolerance to the drug. After administering heroin for a long period, he found that the dosage needed to be increased. He stated that he found "No harmful results, especially as I observed no abstinence symptoms whatever. Generally it appeared that in all cases in which period of time was allowed to elapse the full effect could again be obtained with small doses ... It may be concluded that, regarding tolerance to heroin, certain individuals react peculiarly and it is recommended that in the case of old and feeble persons, the initial dose should not be over 0.005 g."
Horatio C. Wood[13] Jr., 1899, also found that the dosage had to be increased in order to remain effective. He warned that experimentation was still not adequate to warrant the conclusion that heroin was not addiction producing.
In 1901, Joseph Jacobi, basing himself on the use of heroin in 85 cases, claimed the drug as superior as a cough-soothing remedy. Although he found its use more effective with patients who had never used strong narcotic drugs, he reported that any tendency towards tolerance could be averted if dosage was curtailed for several weeks. He also recommended that its use should be alternated with morphine or codeine.
At about this time the enthusiasm for heroin started to wane. Morel-Lavalle[15] in 1902 warned against its habit-forming properties although he thought it safer to use than morphine. Along with many others Morel-Lavalle advocated treatment by heroin in demorphinisation. His practice was criticized by Jarrige[16] in 1902 who claimed that physicians would thus make "heroinists" of their patients. Citing several cases of heroinism, he was emphatic in his contention that the withdrawal of heroin was much more painful than that of morphine. Rather than reducing the use of narcotics, the advocation of heroin was responsible for many persons becoming drug addicts.
In 1903 Pettey[17] reported that of the last 150 cases he had treated for drug addiction, eight were heroin users and of these, three had first become addicts through the use of heroin. He further reported that the heroin habit was just as difficult to cure as the morphine habit.
Sollier,[18] in 1905, deplored the use of heroin in the treatment of morphinism. This practice, he claimed, had resulted in the number of heroin addicts becoming as great as that of morphine addicts. Heroin was extremely toxic and the extent of poisoning in the heroinists he had seen, was much greater than it would have been for the same amount of morphine. Sollier found that the mental and physical deterioration from the use of heroin was very rapid. He opposed its use in the treatment of both morphinism and respiratory diseases.
In the same year Atwood[19] reported a case of heroinism in a woman who had become addicted to heroin after its use in surgery. Although not as vehement as Sollier and Jarrige, Atwood advised caution in prescribing the drug. Atwood believed cases of heroin addiction to be rare, but he pointed out that such cases would become more common if no discretion was used by the medical profession and he was against its prescription for coughs, recurring headaches, rheumatism and other chronic diseases.
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