WHAT IS PHARMACOEPIDEMIOLOGY? cause deaths from liver disease 21 In 1982 behox- histamines terfenadine and astemizole 50,sI aprofen was noted to do the same." Subse- Hypertension, seizures, and strokes were noted quently the use of zomepirac, another from postpartum use of bromocriptine 52.53 nonsteroidal anti-inflammatory drug, was noted Multiple different adverse reactions were linked tto phyl itopid reactions. Serious blood dyscrasias drug was never convincingly linked to, th i X perforations were noted to be caused by a parti- coveries led to the removal of the drug involved cular slow release formulation of indomethacin. from the market. Interestingly, however, this Bendectin, a combination product indicated to withdrawal was not necessarily performed in all treat nausea and vomiting in pregnancy, was of the different countries in which each drug was removed from the market because of litigation marketed. Most of these discoveries have led to claiming it was a teratogen, despite the absence litigation, as well, and a few have even led to of valid scientific evidence to justify this claim 26 criminal charges against the pharmaceutical man- (see also Chapter 9). Acute flank pain and rever- ufacturer and/or some of its employees sible acute renal failure were noted to be caused Each of these was a serious but uncommon by suprofen. Isotretinoin was almost removed drug effect, and these and other serious but from the US market because of the birth defects uncommon drug effects have led to an acceler- it causes. "4 The eosinophilia-myalgia syn- ated search for new methods to study drug drome was linked to a particular brand of L- effects in large numbers of patients. This has led tryptophan. Triazolam, thought by the Nether- to a shift from adverse effect studies to adverse lands in 1979 to be subject to a disproportionat number of central nervous system side effects, event studies In part in response to concerns about adverse was discovered by the rest of the world to be drug effects, the early 1970s saw the development problematic in the early 1990s. Silicone of the Drug Epidemiology Unit, now the Slone breast implants, inserted by the millions in the Epidemiology Unit, which extended the hospital- US for cosmetic purposes, were accused of caus- based approach of the Boston Collaborative ing cancer, rheumatologic disease, and many Drug Surveillance Program by collecting lifetime other problems, and were restricted from use drug g exposure histories from hospitalized except for breast reconstruction after mas- patients and using these to perform hospital tectomy. Human insulin was marketed as one based case-control studies(see also Chapter of the first of the new biotechnology drugs, but 22). The year 1976 saw the formation of the soon thereafter was accused of causing a dis- Joint Commission on Prescription Drug Use, an proportionate amount of hypoglycemia, 36-40 interdisciplinary committee of experts charged Fluoxetine was marketed as a major new impor- with reviewing the state of the art of pharmaco- tant and commercially successful psychiatric pro- epidemiology at that time, as well as providing duct, but then lost a large part of its market due recommendations for the future. The Compl to accusations about its association with suicidal terized Online Medicaid Analysis and Surveil- ideation. 41 4 An epidemic of deaths from asthma lance System was first developed in 1977, using in New Zealand was traced to fenoterol, and Medicaid billing data to perform pharmacoepide- later data suggested that similar, although smal- miologic studies(see also Chapter 15).The ler, risks may be present with other beta-agonist Drug Surveillance Research Unit, now called the inhalers. The possibility was raised of cancer Drug Safety Research Trust, was developed in from depot-medroxyprogesterone, resulting in the United Kingdom in 1980, with its innovative initial refusal to allow its marketing for this system of Prescription Event Monitoring5Each purpose in the US. 7 the conduct of multiple of these represented major contributions to the studies, 8.49 and ultimately drug approval. field of pharmacoepidemiology. A number of Arrhythmias were linked to the use of the anti- other even newer resources have been developed 第173页第 173 页