Hospital admissions due to adverse reactions to Chinese herbal medicines.

Chinese herbal medicines (CHM) are commonly used in Hong Kong. To determine the importance of adverse reactions to CHM as a cause of medical admissions in Hong Kong, all 1701 patients admitted to two general medical wards at the Prince of Wales Hospital over an eight-month period were prospectively studied. In only three patients (0.2%) was the admission attributed to the adverse effects of CHM. These were life-threatening in two cases ('dazao'-induced angio-neurotic oedema and liquorice-induced hypokalaemic periodic paralysis). Despite this low incidence of adverse reactions, in communities where CHM are commonly used, it is important that there is a continuing effort to collect new information on the safety of these compounds.     

Pharmacogenetics and adverse drug reactions

Polymorphisms in the genes that code for drug-metabolising enzymes, drug transporters, drug receptors, and ion channels can affect an individual's risk of having an adverse drug reaction, or can alter the efficacy of drug treatment in that individual. Mutant alleles at a single gene locus are the best studied individual risk factors for adverse drug reactions, and include many genes coding for drug-metabolising enzymes. These genetic polymorphisms of drug metabolism produce the phenotypes of "poor metabolisers" or "ultrarapid metabolisers" of numerous drugs. Together, such phenotypes make up a substantial proportion of the population. Pharmacogenomic techniques allow efficient analysis of these risk factors, and genotyping tests have the potential to optimise drug therapy in the future.     

214例HIV/AIDS病人的HAART不良反应及换药原因分析

目的探讨艾滋病病毒（HIV）感染者/艾滋病（AIDS）病人（简称HIV/AIDS病人）高效抗反转录病毒治疗（HAART）的不良反应及换药原因。为保证HAART合理用药及用药安全提供依据。方法全部病人均使用国家免费艾滋病HAART药物,按照国家免费艾滋病抗病毒药物治疗手册要求,全部病例均在HAART后1、2、3、6、9、12个月随访1次,统计病人不良反应及换药原因,数据分析用SPSS 19.0软件处理,以P〈0.05为差异有统计学意义。结果 95例病人中90例出现抗病毒药物不良反应、3例一线治疗失败、2例因药物配伍禁忌更换抗病毒药物。其中90例病人因AZT、NVP、D4T不良反应更换抗病毒药物。另有3例初始HAART方案包含EFV的病人,出现神经系统症状,均自行缓解,未更换药物。将初始HAART方案包含AZT、NVP、D4T的病例分为未换药组和换药组,将两组病人的基线CD＋4T淋巴细胞（简称CD4细胞）计数值进行统计学比较,差异无统计学意义。结论HAART的主要换药原因为抗病毒药物不良反应。在包含AZT、D4T、NVP的HAART方案中,治疗前3个月着重监测AZT、NVP的不良反应,治疗6个月后着重监测D4T的不良反应,且不良反应的出现与基线CD4细胞计数无关。同时须及早发现耐药,并须掌握药物配伍禁忌。     

Drug therapy and adverse drug reactions

Drug therapy and adverse drug reactions     

Gastrointestinal manifestations of adverse drug reactions

Adverse drug reactions affecting the digestive system were studied by epidemiologic methods. A population of 3164 inpatients and 612 outpatients were monitored for drug utilization and adverse drug reactions. Reactions affecting the digestive system were detected in 4.3% of the inpatients. Women experienced digestive reactions at a higher incidence than men (P<.05). Potassium chloride, heparin, dioctyl sodium sulfosuccinate, and aluminum and magnesium hydroxide suspension were the drugs most commonly cited as a cause of gastrointestinal reactions. A significantly greater rate of gastrointestinal reactions to levodopa (P<.01) and guanethidine (P<.05) were observed in women as compared to men. A similar predisposition to gastrointestinal side-effects of drugs was observed in outpatients where women reported a significantly higher incidence (P<.001) of gastrointestinal reactions as compared to men.Supported by a contract from the Food and Drug Administration and a grant from the National Institutes of Health.     

Hospitalisation and morbidity due to adverse drug reactions in elderly patients: a single‐centre study

Background

Adverse drug reaction (ADR) is a leading but under‐recognised cause of illness, particularly in frail subjects with multiple comorbidities.

Aim

To investigate the frequency, patterns and outcomes of ADR as a cause of hospitalisation in elderly patients admitted to an internal medicine ward.

Methods

We performed a retrospective observational study including every patient aged over 65 years who was admitted to our department during a 12‐month period. Patients admitted to short‐stay (<24 h) observation unit were excluded.

Results

ADR accounted for 106 of total 1750 recorded admissions, which constituted a proportion of 6.1% (95% confidence interval 5.0–7.3%). The median age of patients was 83.5 (78.0–87.0) years and 56.6% were on polypharmacy. A total of 170 ADR was recorded with 45.3% of subjects experiencing concomitantly more than one ADR from a single molecule. Diuretics were the most commonly imputed molecules (30 events, 17.6%), followed by antithrombotics (25 events, 14.7%) and central nervous system‐active drugs (16 events, 9.4%). Interactions were judged responsible for 39 cases of ADR (36.8%). An unfavourable outcome was observed in about one‐third of patients (37.7%). Among those subjects, 11 (10.4%) died and 29 (27.4%) had residual disability.

Conclusion

ADR are a common cause of hospital admission in elderly patients and are often associated with adverse outcomes. Our data underline the need of appropriate strategies aimed at identifying high‐risk patients and avoiding potentially preventable drug toxicities.     

Mortality due to acute adverse drug reactions: opiates and cocaine in Barcelona, 1989–93

Drug-related deaths have become a major source of premature mortality. This paper presents an analysis of deaths due to acute adverse drug reactions caused by opiates or cocaine in the city of Barcelona over a 5-year period during which figures were stable. Annual mortality rates due to adverse drug reactions of city residents for the 1989-93 period were estimated to be 15.3 per 100 000 people in the 15-49-year age group. Mortality rates for men (25.0) are consistently higher than mortality rates for women (5.8). Mortality rates by age group show different patterns by gender. Males in the 25-29-year group have the highest mortality rate (62.8), almost doubling the rates for the 20-24 (36.1) and 30-34 (33.3)-year groups. The highest differential in age-specific mortality by gender is seen in the 35–39-year age group, where mortality rates for men (21.5) are eight times higher than for women (2.6 per 100 000). The distribution by place of residence, stratifying data across city neighbourhoods and municipal districts displays wide differences between districts in the mean annual rates, ranking between 77.3 and 8.3 per 100 000, a nine-fold magnitude. Differences are even steeper when we break down data by neighbourhood. Although all areas with high adverse drug reactions mortality are areas of low socio-economic level, a more complex association between deprivation and drug use must exist, as other areas with similarly low socio-economic indicators do not suffer from such high mortality. A cross-tabulation of place of residence and district of death shows that for most adverse drug reaction deaths, death takes place in the district of residence but patterns related to districts who attract drug-related deaths and districts who export them may be observed. These results provide new insights into the epidemiology of substance abuse in Barcelona, where it follows patterns that may be similar to those of other major urban areas in Spain, but also in other Southern European countries.     

Epidemiology and individual susceptibility to adverse drug reactions affecting the liver

Adverse drug reactions affecting the liver represent an important challenge for safety in drug development. Drugs can reproduce practically the whole spectrum of liver diseases, but acute hepatitis is the most common syndrome. Drug hepatotoxicity is one of the most common causes of fulminant hepatitis. Most hepatic drug reactions occur in only a small proportion of individuals, making them difficult to detect at the time of drug development. Liver injury is principally recognized on the basis of spontaneous reports within the first 2 years of marketing a new drug. The prevalence of drug hepatotoxicity is poorly documented by a small number of retrospective studies. Despite the development of international analytical methods to allow standardized evaluation, the diagnosis remains indeterminate in many cases. Acquired and genetic factors influence the individual susceptibility to drug hepatotoxicity. Important directions for the future include prospective studies of the incidence of hepatic adverse drug reactions, finding specific markers that augment or replace causality assessment, and further elucidating the role of the genetic and environmental factors that contribute to individual susceptibility.     

New concepts in the management of adverse drug reactions.

Our understanding of drug reactions and their management has changed markedly in recent years with the development of several new concepts. Epidermal cell death seen in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) may result from Fas-Fas ligand-mediated apoptosis. Intravenous immunoglobulin (IVIG) contains anti-Fas antibodies that can abrogate apoptosis. Most studies on IVIG in SJS and TEN reported improvement in arresting disease progression and reduction in time to healing. Furthermore, several studies have dispelled the myth of sulfonamide cross-reactivity. Immune-mediated reactions against antibacterial sulfonamides are directed against two unique side chains that non-antibacterial sulfonamides do not contain. Certain patients seem to have a genetic predisposition for "multiple drug sensitivities." Hence, they may react to several drugs that are not necessarily cross-reacting. Also, multiple studies have shown that IgE-mediated nonsteroidal anti-inflammatory drugs (NSAIDs) cross-reactivity is uncommon. Rather, it is cyclooxygenase (COX) 1 inhibition that results in pseudoallergic reactions to multiple NSAIDs. Several studies have indicated that selective COX-2 inhibitors can be safely administered in patients with aspirin-exacerbated respiratory disease and NSAID-induced cutaneous reactions, although their use has been curtailed by their cardiovascular side effects. Biological agents, such as infliximab, are being increasingly used for a variety of diseases and have caused adverse reactions in some patients. Studies differ as to whether concomitant immunosuppressive use with infliximab affects the development of drug-specific antibodies and infusion reactions. Successful desensitization protocols have been developed for reactions to some of these agents.