Adverse Drug Reactions and Toxicological Reviews

P.F. Darcy

James McElnay

ADVERSE DRUG-REACTIONS AND THE ELDERLY PATIENT

药物不良反应与老年患者

Physician, traveller, writer and spy, Andrew Boorde was born c1490 and became a Carthusian monk after abandoning his medical studies at Oxford. Temperamentally unsuited to the life of a religious, after 20 years at the London Charterhouse he obtained a dispensation to travel to Europe to continue his medical studies. Returning to England he began to practise medicine, treating members of the nobility and, through a meeting with Thomas Cromwell which was to influence the rest of his life, he attended the King, Henry VIII. In 1534, after a second, more extensive, tour of Europe in which he visited many medical schools and universities seeking yet more medical knowledge, he returned to the London Charterhouse which was undergoing a brutal dissolution at the hands of Thomas Cromwell. Boorde reluctantly signed the Oath of Supremacy, an act which was to haunt him for the rest of his life. He was then used by Cromwell to travel abroad again but this time as a spy to gather intelligence for the King while continuing to study medicine. Boorde finally took his MD at the University of Montpellier and was incorporated in the same degree a year later at Oxford. He then gave expression to all he had learnt by writing his legacy, four books which were published in 1547. 'A Compendyous Regyment or a Dyetary of Health' was one of the earliest treatises on the cultivation of health composed in England and stressed the importance of sanitation together with a detailed examination of diet. The 'Brevyary of Health' listed diseases alphabetically together with remedies and treatment, blending sound medical advice with religion and superstition: its companion volume was 'The Principles of Astronomy'. But Boorde's 'Fyrst Boke of the Introduction of Knowledge' was his tour-de-force; it was a comprehensive encyclopaedia of all the European countries he had visited, illustrated by woodcuts. By 1547 Boorde was settled in England, probably Master of the Hospital of St Giles-in-the-Fields in London but by 1549 he was living the life of a recluse in Winchester. Tortured by guilt at his perceived lack of religious integrity and persecuted by his enemies he died in the Fleet prison amid rumors that he had poisoned himself.

Patricia E. S. Fletcher

Adverse Drug React Toxicol Rev

The Life of Andrew Boorde, c1490–1549

安德鲁·博尔德的生活，约1490-1549年

There is a rapidly growing trend in the consumption of herbal remedies in industrialised and developing countries. Users of herbal remedies are at risk of toxicity and adverse interactions of herbal preparations due to their frequent contamination with metals and adulteration with synthetic drugs. The purpose of this study was to assess the quality of herbal remedies present on the market in Saudi Arabia in recent years.

Maciej J. Bogusz

Mohammed Al Tufail

Huda Hassan

How Natural Are ‘Natural Herbal Remedies’?

“天然草药”有多天然？

Plant sources of some traditional Chinese herbs may have changed over time. History records of herbal toxicity should be viewed critically when different plants might have been used under the same name in earlier eras. The current main source of the Chinese herb Mu Tong is Aristolochia manshuriensis. Examination of classical Chinese herbal literature revealed that until the mid 17th century the original source plants of Mu Tong had been several Akebia species. From the 17th century until the early 20th century Clematis species were the main source of Mu Tong. A manshuriensis has only been widely used since the 1950s. Renal failure due to ingestion of large doses of A. manshuriensis has been reported in China and other countries while no such toxicity has been recorded in traditional Chinese herbal texts. Documentation of traditional Chinese herbal literature should help to ensure the safe use of Chinese herbs.

You-Ping Zhu

Toxicity of the Chinese Herb Mu Tong (Aristolochia manshuriensis)

中药木通（关木通）的毒性

Antipsychotics are frequently associated with QTc interval prolongation, a proposed marker for vulnerability to fatal ventricular arrhythmias, e.g. torsade de pointes (TdP). Little has been published on this topic in relation to clozapine. The objectives of this review were to: (i) calculate the frequency of QTc interval prolongation, T-wave abnormalities, TdP, ventricular tachycardia/fibrillation and sudden unexplained death in patients treated with clozapine and thioridazine from clinical trial and post-marketing reports; (ii) to compare these data with published findings for haloperidol, risperidone, olanzapine, sertindole and ziprasidone; and (iii) to correlate these clinical data with results from preclinical tests presently considered to be of predictive value for a compound's potential to cause QTc interval prolongation and TdP. A review of the global Novartis databases for clozapine and thioridazine and a Medline/Internet search for information on these cardiac events and for preclinical effects on the human ether-a-go-go related gene channels, action potential duration, and QT interval changes produced by the selected antipsychotics were performed. The clozapine database (2.8 million patient-years spanning 27 years) demonstrated that at therapeutic doses all but three reports of QTc interval prolongation and both of TdP were confounded by relevant co-medication/comorbidity. The literature review revealed that all antipsychotics considered except clozapine induced TdP and/or QTc interval prolongation at therapeutic doses. Preclinical in vitro tests appear to overestimate the risk of clozapine, haloperidol and risperidone to prolong QTc interval in patients and underestimate such a risk for sertindole and ziprasidone. Extrapolation of in vitro results to clinical events requires qualified interpretation.

Barbara Warner

Peter Hoffmann

Investigation of the Potential of Clozapine to Cause Torsade de Pointes

氯氮平引起尖端扭转型室性心动过速的潜在风险研究

This review provides an updated overview of the adverse effects of sulphonylureas and identifies factors associated with variation in adverse effect rates among sulphonylureas published by different studies. A search of Medline, Embase, Current Contents and Cochrane Library was conducted to identify all papers related to sulphonylureas and adverse effects published from 1950-2001. The reference lists of all relevant papers were also searched for additional articles. The frequency of sulphonylurea-induced hypoglycaemia varied from 1.8-59%. Severe hypoglycaemia due to sulphonylurea use has been reported from 1.9-3.5%. Variation in hypoglycaemia rates may be due to differences in definitions, methods to detect and to collect information, patient characteristics, patient knowledge of the condition, threshold for symptoms, and activity level during hypoglycaemia. Other adverse effects associated with sulphonylurea use include bodyweight gain, gastrointestinal distress, disulphiram-like syndrome, dermatological reactions, haematological changes, ocular problems, and the syndrome of inappropriate secretion of antidiuretic hormone. Bodyweight gain has been reported to vary from 1.7-4.8 kg, according to the United Kingdom Prospective Diabetes Study (UKPDS-33). Controversy exists regarding cardiovascular adverse effects, but the consensus is to exercise caution in the use of these drugs as first-line therapy for patients with diabetes mellitus and coronary artery disease. The benefits of sulphonylurea treatment should be weighed against the risks associated with them. More work in this area is needed to homogenise the definition of hypoglycaemia, to get consensus on the methods for detection and data collection, as well as to further patient and physician education.

Maribel Salas

Jaime J. Caro

Are Hypoglycaemia and Other Adverse Effects Similar Among Sulphonylureas?

磺脲类药物的低血糖和其他不良反应是否相似？

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ADVERSE DRUG-REACTIONS AND THE ELDERLY PATIENT

ADVERSE DRUG-REACTIONS AND THE ELDERLY PATIENT

ADVERSE DRUG-REACTIONS AND THE ELDERLY PATIENT

ADVERSE DRUG-REACTIONS AND THE ELDERLY PATIENT

ADVERSE DRUG-REACTIONS AND THE ELDERLY PATIENT

The Life of Andrew Boorde, c1490–1549

How Natural Are ‘Natural Herbal Remedies’?

Toxicity of the Chinese Herb Mu Tong (Aristolochia manshuriensis)

Investigation of the Potential of Clozapine to Cause Torsade de Pointes

Are Hypoglycaemia and Other Adverse Effects Similar Among Sulphonylureas?