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Antioxidants in Nutrition, Health, and Disease

John M.C. Gutteridge, Barry Halliwell
Oxford University Press, 70 Wynford Dr, Don Mills, ON M3C 1J9
1994/143 pp

Strengths

Summarizes current thought on free radicals and antioxidants. A clear, pithy, scientific, informative text

Audience

Physicians, medical students, nurses, biologists, nutritionists, and chemists

The authors have written a short textbook introducing antioxidants to clinical practice. They also refresh readers with a review of the basic clinical sciences.

A short, informative preface asks succinct questions on using antioxidants for treating heart disease, cancer, and degenerative illnesses. The authors answer their questions with sufficient information on free radicals, cholesterol, and oxidative stress for readers to use in laboratories and practices.

A historical discussion of oxygen, oxidation-reduction definitions, and electron transport is followed by scientific information on the Krebs cycle, vitamins, and nutrients and a timely presentation of free radicals as contributing to cardiovascular and degenerative disease.

Later, epidemiologic and pathologic evidence on nutrient use is presented. This evidence allows us to understand information applicable to a scientific study of tissue damage and regeneration. Clearly, interest in the effects of nutrition and vitamins on health has increased. This short text will help practitioners upgrade current knowledge and share the information with patients.

The authors acknowledge the brevity of their text. They have challenged readers to examine modern concepts that might be discussed with our patients in the office. They also give us sufficient information to provide our patients and colleagues with current thinking on the activity of essential vitamins A, E, and C.

The style of this book flows well with diagrams, bold headings, illustrations, and informative tables. I enjoyed the quotations from The Beatles and Butch Cassidy and the Sundance Kid mixed with Paracelsus and Francis Bacon, which set the tone for the discussion in each of the seven chapters.

Appendices supplementing chapters 1, 4, and 5 provide further information on cholesterol, saturated and unsaturated fats, and their effect on the cardiovascular system. The authors raise questions not only for academics, but also for the less scientific. Skillfully, they then lead us through a historical discussion of the building blocks of life: carbon, hydrogen, oxygen, and nitrogen. Are antioxidants elixirs or media hype? Are human phagocytes useful? Does oxidative stress help or hinder our health? Should vitamins and minerals be used as supplements? What is the window of optimum activity of antioxidants?

Although the jury is still out on the results of antioxidant research, the authors present much food for thought. This book is valuable, and a few nights’ perusal should give readers sufficient vital information on antioxidant therapy to guide application.

Introduction

Most general practitioners (GPs) will be familiar with the sometimes perplexing problem of trying to decide whether a patient’s symptom is owing to an adverse drug reaction, to a symptom of the presenting illness, or to an unrelated illness. There is a large quantity of literature on the subject of adverse reactions associated with individual drugs and about adverse drug reactions in hospital inpatients; however, there has been little recent information about adverse reactions to drugs in the community. In 1973 Mulroy reported that one in 40 general practice consultations was the result of iatrogenic disease and a few years later Martys, looking specifically at the incidence of adverse drug reactions, found that 41% of patients have some form of adverse reaction to a prescribed drug.

This small practice-based study aims to assess the impact of adverse drug reactions in general practitioner consultations.

Method

Dingwall Medical Group is a rural general practice in the Scottish Highlands with a practice population of 11 201. The Scottish Prescribing Analysis (SPA) figures for the six-month period of this study showed the average cost per patient to be 1% below the Scottish average.

During the six-month period between April and September 1999, all doctors working in the Dingwall practice were asked to record any suspected adverse drug reactions in patients in whom an adverse drug reaction was a presenting symptom, using a simple data collection form. The definition of an adverse drug reaction was that used by the World Health Organisation (WHO), i.e. ‘any noxious, unintended or undesired effect of a drug which occurs at doses used in humans for prophylaxis, diagnosis or therapy’. As well as meeting the WHO classification, suspected adverse drug reactions had also to be datasheet-listed as a possible side-effect of the drug to be included in the analysis.

In an attempt to estimate the proportion of eligible cases that failed to be recorded by the participating doctors, two validation searches of patients’ notes were carried out by an independent, experienced research nurse. This validation exercise was carried out on two separate three-day periods at times unknown to the participating doctors. It showed a level of under-reporting of 27%.

Results

During the six-month period, 272 adverse drug reactions were recorded in a total of 16 253 routine and extra appointments, giving a consultation rate with this problem of 1.7%. One patient was admitted to hospital and two patients attended accident and emergency departments with suspected adverse drug reactions. One yellow card was completed. Fifty-two (19%) of the patients had a previously documented adverse drug reaction in their medical notes; in five cases the offending drug was contraindicated. One hundred and ninety-three (71%) drugs with suspected adverse reactions were stopped; in seven cases the symptoms persisted. Doctors reported adverse drug reactions as being probable (i.e. almost certainly a symptom caused by the drug rather than the illness) in 197 (72%) and possible (i.e. a symptom that might have been caused by the drug rather than the illness) in 75 (28%) cases.

Analysis of the reported adverse reactions showed that 50% were accounted for by three groups of drugs: antidepressants, antibiotics, and non-steroidal anti-inflammatory drug (NSAID)-containing agents. However, scrutiny of the practice’s SPA data showed that these three groups of drugs accounted for only 13.6% of the prescriptions written during the six-month study period.

Table 1 shows the top ten presenting drugs with adverse drug reactions as an event rate. Four of the top five presenting drugs are new serotonin selective reuptake inhibitors (SSRIs) or related antidepressant agents. Analysis of the practice’s total antidepressant prescribing pattern shows that during the study period 63% of the antidepressants prescribed belong to the SSRIs and related compounds and 37% were tricyclic antidepressant or related drugs.

Table 1. Top ten presenting drugs with adverse drug reactions as an event rate, i.e. number of adverse drug reactions divided by the total number of times the drug was prescribed, expressed as a percentage. The average daily dose for patients presenting with adverse reactions to these drugs is also listed.

Discussion

The results from this study suggest that presentation with an adverse drug reaction is a common reason for patients consulting their GR. The consultation rate of 1.7% is almost certainly an underestimate of the true rate. The validation exercise carried out during the study period would suggest that a rate greater than 2% is more likely. This is a rate similar to that expected for patients presenting with ‘dizzy spells’ or migraine.

The other main finding was that 50% of adverse drug reactions were accounted for by only three groups of drugs, i.e. antidepressants, antibiotics, and NSAIDs. Martys, in his survey of the incidence of drug-induced disease in general practice 20 years ago, also found high rates of adverse drug reactions with these drugs.

The current study suggests that there is a particular problem with SSRIs and related drugs, that have been introduced in this country in recent years and are being more frequently prescribed in general practice. One of the justifications for their use is a better side-effect profile and tolerability compared with tricyclic antidepressants. This was not borne out in the current study.

There were no reported difficulties in using the WHO definition of an adverse drug reaction but it was not possible to verify the accuracy of suspected adverse reactions, except to note that on follow-up only seven cases were still symptomatic after stopping the drug. Likewise, the distinction between a probable and possible adverse reaction is highly subjective but herein lies the dilemma that general practitioners are presented with every day. The adverse reaction is often mild or self-limiting but the offending drug is usually stopped. The decision to stop the drug is probably based on the GP’s assessment of the risks/benefits of continuing treatment and the patient’s wishes. We need to know more about how general practitioners approach this problem.

Big gainer: persons with cardiovascular diseases.

The good news for many Americans is that persons with diseases treatable by drugs, such as stomach ulcers and hypertension, are living longer. The death rate from these diseases has plunged thanks to the introduction of beta-blockers, proton pump inhibitors, and other drugs. A recent study in JAMA found that nonsmokers who comply with their drug therapy and who thereby maintain normal blood pressure and cholesterol levels can add 6 to 9 years to their lives. As the chart shows, the death rates from rheumatic fever and heart disease, atherosclerosis, stomach ulcers, ischemic heart disease and emphysema have significantly decreased between 1965.

Breakthrough Drugs

Breakthrough medications and vaccines have had a tremendous impact on longevity in the past 65 years. First came the anti-infective drugs, such as sulfa in 1935, that set the stage for the development of penicillin. The years between 1938 and 1953 are heralded as the “Age of Antibiotics?because of the large number of anti-infective agents introduced. Vaccines then followed as the major force in eradicating deaths from diphtheria, syphilis, whooping cough, polio, and measles. Since 1920, the combined death rate from the flu and pneumonia has been reduced by 85%.

Recent Advances

New discoveries in genetics are leading to advances in therapies for cystic fibrosis, Parkinson’s disease, and cancer. In 1997, the death rate from AIDS dropped by nearly half, the biggest single-year decline in history for a major cause of death. These advances are coming in time to prevent a major “epidemic?in disease as the Baby Boom population ages. Demographic trends indicate that more than 50 million Americans past age 65 will be at risk for various degenerative diseases by 2050. But the fact is that today Americans can expect to live more than 76 years. In 1920 life expectancy at birth was 54 years. For every 5 years since 1965, an additional year has been added to life expect