Health and Pills

Arthrotec is a new product that combines the NSAID diclofenac and the prostaglandin analog misoprostol. The diclofenac component of Arthrotec is responsible for the relief of the symptoms of arthritis. The misoprostol component is responsible for the mucoprotective properties. Arthrotec has the dual purpose of relieving the signs and symptoms of arthritis and protecting patients from the development of gastric and duodenal ulcers.

It is available in two strengths. One formulation (Arthrotec 50) contains 50 mg of diclofenac and 200 mcg of misoprostol while the other (Arthrotec 75) contains 75 mg of diclofenac and 200 mcg of misoprostol. The usual dose of Arthrotec in the management of osteoarthritis is 50 TID and for rheumatoid arthritis is 50 TID or QID; BID dosing can be used.

How it works:

Diclofenac sodium:

Diclofenac sodium is an NSAID that exhibits classical anti-inflammatory, antipyretic, as well as analgesic properties. As with other NSAIDs, its exact mechanism is not completely understood but it is believed that diclofenac, like other NSAIDs, works in part by inhibiting prostaglandin synthetase.

Misoprostol:

Misoprostol is a synthetic prostaglandin E1 analog. In animals, misoprostol inhibits gastric acid secretion and promotes mucosal protective properties. Misoprostol can increase bicarbonate and mucus production and decrease the secretion of gastric acid. The exact reason for protection against ulcers has not be determined.

Clinical Tips

Diclofenac:

Diclofenac is completely absorbed through the gastrointestinal tract following oral administration. The diclofenac portion of Arthrotec is stable in the acidic environment of the stomach. However, it is rapidly released from the formulation once it enters the more basic environment of the duodenum. Peak plasma levels of this portion are reached in about 2 hours. Because of the extensive first pass effect, only 50% of the dose is available for absorption. The diclofenac portion of Arthrotec is metabolized by the liver and cleared by the urine (65%) and the biliary route (35%).

Misoprostol:

Misoprostol is rapidly absorbed following oral administration, but must undergo metabolic activation into misoprostol acid before it can exerts it pharmacologic actions. The misoprostol acid that is present in Arthrotec reaches peak plasma levels in about 20 minutes and is rapidly eliminated with an approximate half-life of 30 minutes.

Arthrotec follows similar pharmacokinetic parameters as the individual components. The amount of absorption of the two components from the preparation of Arthrotec is comparable to the amount of absorption of the two individual components separately. Importantly, food tends to decrease the bioavailability of the two components of Arthrotec. The pharmacokinetic profile of the diclofenac component in Arthrotec is unchanged in elderly patients and in patients who are renally and hepatically challenged. The pharmacokinetics of misoprostol is influenced by age as well as renal and hepatic impairment; the levels of misoprostol in these individual may double. Hence, it is necessary to adjust the dose in elderly patients and in patients who have renal and hepatic problems.

Clinical studies have shown that diclofenac alone, or in combination with misoprostol, is effective in the treatment of the signs and symptoms of osteoarthritis and rheumatoid arthritis. When given alone, misoprostol has been shown to reduce the occurrence of gastric and duodenal ulcers in patients who were receiving a variety of NSAIDs for the management of arthritic conditions. When Arthrotec was compared to diclofenac alone in patients who had osteoarthritis, the incidence of drug-induced ulcers was lower in patients who were receiving Arthrotec than those who were receiving diclofenac. Even though the incidence of gastric and duodenal ulcers was lower with Arthrotec, only the incidence of gastric ulcers was significantly lower in patients who were receiving Arthrotec than those who were receiving diclofenac.

Abdominal pain, diarrhea, upset stomach, and nausea are among the most common side effects with Arthrotec. Diarrhea may be reduced if this medication is taken with meals. Most adverse effects that occur with misoprostol are mild to moderate and generally resolve following a few days of treatment.

Instructions for the Patient

Arthrotec should not be given to patients who are allergic to aspirin, who have pre-existing asthma, and who have severe renal failure. It should not be given to patients who are pregnant or who are planning to become pregnant because it is believed the misoprostol component can cause fetal death.

Patients should also be advised to swallow Arthrotec whole; they should not chew, crush or dissolve this medication. In addition, patients should be advised to report any signs and symptoms of liver failure (jaundice, itching, nausea) to their physician.

A new study concludes that the osteoarthritis drug Vioxx(R) (rofecoxib) is both safe and effective in relieving the pain associated with menstrual cramps.

• researchers at the Merck Research Laboratories compared the effects of rofecoxib to those of both the non-steroidal anti-inflammatory drug (NSAID) naproxen sodium and placebo in 127 women, aged 18 and older, who had histories of moderate to severe menstrual pain.
• found that menstrual pain at eight and 12 hours after medication was relieved similarly in both rofecoxib and naproxen sodium recipients.
• side-effects were similar among all three groups in the study.
• authors note that menstrual pain is thought to be caused, at least in part, by substances called prostaglandins, and that rofecoxib works to reduce the production of prostaglandins by inhibiting the COX-2 enzyme.

The Facts about Drug Use

Dr Barry Stimmel, The Haworth Medical Press, 10 Alice St, Binghamton, NT 13904-1580, USA, 1993, 366pp

Family physicians often see patients who misuse drugs. This widespread problem is the source of much hidden morbidity and mortality for patients and much frustration for doctors.

Family doctors are likely to have had little formal training in identifying and intervening in this area. Their attitudes toward problem drug use probably differ little from those held by the public.

This book was written “to enable those with little or no background in science or health care to understand the often complex issues of drug use” and “is presented clearly, concisely, and without jargon.” It presents the facts about drug use with authority.

The book is divided into three parts: basic concepts, mood-altering drugs, and areas of special concern. Information is based on statistics from the United States. The regulations and laws quoted are American. Treatments discussed are based on the American system of privately funded health care.

In part 1 (basic concepts), the chapter titled “Habituation, Dependency and Addiction” is useful for defining terms and distinguishing misuse from abuse and dependency from addiction. This chapter briefly describes the neurophysiological basis for the ability of drugs to produce mood alteration, which can lead to dependency and addiction.

Part 2 discusses each different class of mood-altering drugs and provides lots of factual information. However, the chapter on opiates underemphasizes their importance as drugs of abuse in clinical practice while the chapter on heroin and on methadone maintenance is too long. In the chapter on nicotine, the nicotine patch is referred to only briefly.

In part 3 (areas of special concern), well written, factual chapters cover such topics as drugs and AIDS, drugs and pregnancy, and drugs and sports. The final chapter is one with a decidedly American slant entitled “Why has the War Against Drugs Failed?”

Three appendices covering sources for reporting drug use (American), drug testing technology, and common street names for drugs are followed by almost 400 references. This book is not written for family physicians. It does not develop skills for identifying problems or intervening in this area or even challenge attitudes. However, it would be useful for family doctors interested in the facts on drug use and as an addition to a hospital, school, or public library.

Essentials f Drug Therapy

Gordon E. Johnson, PHD W.B. Sounders Company, 55 Homer Ave, Toronto, ON M8Z 4X6, 1991, 425 pp

Essentials of Drug Therapy is a clearly written book, summarizing information on drugs that are commonly used. It is not a reference text in pharmacology or an exhaustive detailed volume, such as the Compendium of Pharmaceuticals and Specialties, but is a practical source of information for the medical student and practitioner.

The chapters are organized according to therapeutic categories and are introduced by a brief overview of the therapeutic rationale for use of pharmacologie agents. Most drug groups are included, even those used for symptomatic relief, such as antitussives and analgesics. It is somewhat surprising that laxatives are not included, but these have never been an attractive group of drugs for pharmacologists.

The text is clear and succinct. Paragraph headings facilitate rapid access to information, with paragraphs on mechanism of action and pharmacological effects, therapeutic uses, adverse effects, drug interactions, and doses.

The book should be a useful volume for the busy practitioner and the medical student.

Drug-induced hepatotoxicity

Ed by RG Cameron, G Feuer, FA de la Iglesia, 681 pp, ISBN 3 540 60201 1, Berlin: Springer Verlag 1996

The editors of this splendid volume have invited an international array of contributors to cover its 26 chapters on all aspects of hepatotoxicity due to drugs — adverse effects that mimic acute fulminant hepatitis, chronic active hepatitis, cirrhosis and even malignancy. Turn to one of these chapters for an update on molecular aspects of hepatic drug reactions, in vitro models, cytochrome P450, drug-induced cholestasis, choline deficiency, the fatty liver, immune mechanisms, encephalopathy, pregnancy, Reye syndrome, or hepatotoxicity in infants and the elderly; and, of course, for separate information on each individual drug, including one of the most important, alcohol.

This new Canadian text naturally invites comparison with an Australian text, Drug-induced Liver Disease, edited by GC Farrell (Churchill Livingstone), published in 1994. They are both very good and equally helpful when asked to solve a laboratory or clinical problem. Australian Ian Mackay contributes the immune mechanisms of drug hepatotoxicity in both books. To his credit they are in many respects different. In the earlier book he mentions the Th1 and Th2 subclasses of CD4 helper T cells. In the new Canadian book he advances his thoughts and forecasts that tipping towards Th1 or Th2 subsets influences the mode of expression of allergies and autoimmune diseases.

Both books will undoubtedly achieve new editions, so that each will leapfrog the other effectively in different segments of the Commonwealth in the long-term future. It is true to say that clinicians and pathologists have combined admirably to cover the whole gamut of adverse reactions in a single volume which is authoritative, academic and readable.

Complete Guide To Women's Health

Author: American Medical Association
Random House of Canada, Ltd, 1265 Aerowood Dr, Mississauga, ON L4W1B9
1996/759 pp

Good starter guide to women’s health

Strengths

Well formatted, easy to read, practical approaches to common problems, focus on wellness and preventive health

Audience

General public

This comprehensive reference volume for women contains common-sense approaches to a number of important health issues. Its target audience is middle-class American women with a moderately high level of literacy. The book aims to provide women with up-to-date medical information to guide decision making and to facilitate communication with their physicians.

Its four main sections cover health maintenance, sexual and reproductive health, pregnancy, and the common health concerns of women. It is well laid out with useful summaries, flow charts, sidebars containing helpful hints, questions women often ask, and narrative vignettes that lend a dynamic and personal tone to the main text.

I found the chapters on nutrition, fitness, avoiding risky behaviour, and stress management refreshingly frank and practical. The sections on pregnancy and childbirth are well illustrated and cover many of the issues women enquire about in my own practice. Although there are excellent chapters on family violence, sexual assault, and bereavement, the social context of women’s health is not explored in sufficient depth. The short section on sexual abuse, for example, makes only passing mention of the health consequences that an adult survivor of abuse might experience. In contrast, the 19 pages on elective cosmetic surgery seemed excessive.

The book is written with a specialty focus, emphasizing early referral. Very little is said about family physicians and their potential for providing comprehensive care and building health partnerships with women over time. There are no references or suggestions for further reading for women who wish to pursue controversial or rapidly changing issues, such as prevention guidelines. It is also unclear how consultants evaluated the evidence behind their recommendations. I found it surprising, for example, to see episiotomy presented as a procedure to prevent excessive tears during childbirth when there is evidence in the literature to the contrary.

The overall strength of this publication is its range, its detail, and its attention to the prevention of illness, making it a good starting place for many women to access health information and to consider dialogue with their physicians. In this regard, it fulfils the authors’ objectives. Because of its expense and likelihood of dating quickly, I would recommend it as a resource volume for a public library or community health clinic.

Atlas Of Clinical Diagnosis

M. Afzal Mir
W.B. Saunders Company, 55 Horner Ave, Toronto, ON M8Z 4X6
1995/266 pp

Strengths

Practical, excellent illustrations

Audience

Medical students and practitioners

This book aims to provide medical students and practitioners with a comprehensive survey of clinical signs organized by external body parts. The underlying assumption is that most diagnoses from clinical signs are based on pattern recognition, so the book is a rich collection of colour illustrations of common, rare, and esoteric conditions. Using arrows to highlight the more subtle signs would help readers, like me, who need more guidance.

The organization of the book is excellent with a logical approach to each external body part; for example, the chapter on the external eye deals with eyelids and orbit and the conjunctiva. Some interesting clinical tips include listening to a patient’s breathing by putting the stethoscope bell in front of the patient’s mouth.

The focus at times is esoteric with eight pages on various porphyrias, something I was taught in great detail in medical school and have yet to see in practice. Useful diagrams for such conditions as acromegaly or Cushing’s disease illustrate that clinical signs from each anatomical area are only part of the overall picture. Suggestions for further investigation of these major conditions are given but are brief and superficial. Common conditions seen in family practice, such as viral exanthemas, otitis media, and pharyngitis, are given less coverage, and there is a paucity of penile or vulval lesions.

The book is a good reference for unusual conditions and has excellent chapters on fundi, nail disorders, and hands. But the high price of the book could limit how widely it is used.

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.

The physician should inform the guardian of the most frequent expected side-effects and the likelihood of the most untoward effects (Tables 2-4). The discussion of benefits and risks should be noted in the patient record.

Serious side-effects are usually related to dosage and duration of psychotropic medication. Intelligence and learning ability are affected when dosage exceeds optimum levels, usually associated with sedation or toxic effects. Behavioural changes, including irritability, temper tantrums, hyperactivity, or hypoactivity, however, may occur at lower dosages than those that produce even mild somatic complaints. These may be so irksome and so long-lasting that the particular drug must be discontinued.

The most dangerous effects of the major tranquilizer drugs (neuroleptics) are the central nervous system effects. Most effects will subside dramatically if the dose is reduced or if anticholinergic medication is added immediately (anticholinergic medication should not be given preventively, however, before symptoms occur). Neurological symptoms may include acute dystonic reactions, dykinesias, parkinsonian reactions, akathesia, and the “rabbit” syndrome (perioral chewing).

The most malignant of these conditions, tardive dyskinesia, involves involuntary movements of the face, eyelids, upper and lower extremities, fingers, toes, torso, and neck, and can occur as early as within three months of cumulative drug usage. The effect can occur during drug administration or after dose reduction or drug withdrawal. This condition is resistant to treatment with anticholinergic or other medication. It is difficult to differentiate tardive dyskinesia from withdrawal dyskinesia, in which the symptoms may abate within six months. It is worth noting that the poor responders to neuroleptics are the most likely to develop the dyskinesias. This emphasizes the importance of the physician’s evaluating the response to a psychotropic drug within the first month and preferably within a week of the first dose of some medications.

In general, prescription should begin at the lowest dosage. Give an adequate trial at each succeeding dosage level. Recognize that stimulants show an effect within hours, tranquilizers within days, and antidepressants sometimes not for weeks. Therapeutic blood levels for some psychotropic drugs may not be obtained routinely in clinical laboratories. Dosage for children and adolescents is more idiosyncratic than adults. Failure of one drug in a class of psychotropic drugs does not rule out using another drug in that same class. A general rule is not to use two or more drugs from the same class at once to guard against synergism. Usually dosage is increased until effective, which may sometimes be close to the level at which toxic signs appear.

Psychotropic drugs should not be discontinued quickly to minimize the occurrence of seizures or other withdrawal symptoms. “Drug holidays” should be discussed far in advance in order to assess the best opportunity for discontinuation.

Effectiveness should be judged on a weekly basis, with renewal of prescription on a monthly basis. Discontinuation of medication should be considered every three months. The responsibility of monitoring the risk-benefit ratio of long-term psychotropic drug use (for more than three months) must be shared with the guardians.