How to Avoid Dangerous Medication Prescribing Practices

Sudeep Gill, MD, FRCPC
Fellow, Division of Geriatric Medicine,
University of Toronto, Toronto, ON.

Barbara Liu, MD, FRCPC
Kunin-Lunenfeld Applied Research Unit,
Baycrest Centre for Geriatric Care,
Sunnybrook & Women's College Health Sciences Centre,
Assistant Professor of Medicine,
University of Toronto, Toronto, ON.

An adverse drug reaction (ADR) is defined as any noxious or unintended reaction to a drug that is administered in standard doses for the purpose of prophylaxis, diagnosis or treatment.¹ ADRs are common in the elderly--it is estimated that 10-17% of hospital admissions for older patients are directly related to ADRs. Furthermore, one in every 1,000 older inpatients dies as a result of complications of medication use. Many of these ADRs result from potentially inappropriate--and therefore avoidable--drug prescribing practices. In this article, we explore the following topics: pharmacokinetic changes that accompany aging; symptoms and signs that may lead to recognition of ADRs; risk factors that predispose to ADRs; and finally, an approach to appropriate drug prescribing in the elderly.

Drug Pharmacokinetics
Pharmacokinetics involves drug absorption, distribution, metabolism and excretion. With normal aging, there is no clinically significant decline in absorption.

Discontinuing or Switching Psychotropic Therapy for Older Patients: Is Tapering Necessary?

Monica Lee, BSc (Phm), MSc
Research Pharmacist
Baycrest Centre for Geriatric Care,
Toronto, ON.

Julie Dergal, MSc
Kunin-Lunenfeld Applied Research Unit
Baycrest Centre for Geriatric Care,
Toronto, ON.

Introduction
Older people often take multiple drug therapies for the treatment of various, concomitant chronic conditions. As a result, older adults are at increased risk of developing adverse drug events. It is important for physicians to regularly review the drug regimen of any older patient, and to discontinue any drug therapies that are no longer required or indicated. Physicians may also have to discontinue a particular drug therapy for other reasons including: if the drug therapy is ineffective; if it causes intolerable adverse effects; if newer and safer alternative drug therapies become available; or if the patient refuses to continue the treatment. It is important that physicians know how to appropriately discontinue or switch an older person's drug therapy in order to avoid adverse events.

There are currently limited practice guidelines available for discontinuing or switching psychotropic drug therapies. When discontinuing a medication, physicians need to consider whether it can be withdrawn abruptly or gradually tapered.

A New Treatment for Patients with Alzheimer Disease

G. Tong, MD, PhD
Jody Corey-Bloom, MD, PhD
Department of Neurosciences,
University of California San Diego, CA, USA.

Introduction
Alzheimer disease (AD), the most common form of dementia in the elderly, is characterized clinically by multiple cognitive deficits, including memory loss, visuospatial impairment, disorientation and language dysfunction. These features are often accompanied by behavioural and mood changes. A definitive diagnosis of AD can only be made by biopsy or autopsy. The major neuropathological features of AD are neuritic plaques and neurofibrillary tangles.

Cholinergic neurotransmission in the central nervous system (CNS) plays a key role in memory, attention, learning and other cognitive processes. Although other neurotransmitter deficiencies (e.g., noradrenaline, dopamine, serotonin and glutamate) have been noted, the cognitive impairments seen in AD patients have been largely attributed to decreased cholinergic neurotransmission. AD, in part, is characterized by the loss of neurons in basal forebrain cholinergic cells, especially in the nucleus basalis of Meynert, which projects to the cerebral cortex and hippocampus.

Antithrombotic Drugs for Secondary Stroke Prophylaxis

A Review of Efficacy, Toxicity and Safety Considerations

Charles L Bennett, MD, PhD
The Chicago VA Healthcare
System/Lakeside Division, the Robert H Lurie Comprehensive Cancer Center and
the Division of Hematology/Oncology of the Department of Medicine,
Northwestern University,
Chicago, IL, USA.

Richard H Bennett, MD
Department of Neurology,
Albert Einstein Northern Hospital and
the Medical School of the University of Pennsylvania,
Philadelphia, PA, USA.

Introduction
Stroke is a common cause of morbidity and mortality in older adults in the United States and Canada. Fortunately, in both countries, the age-adjusted national death rate for stroke has declined, reflecting increasingly widespread use of primary and secondary prophylaxis efforts. The mainstay of stroke prevention is the use of antiplatelet agents which interfere with thrombus formation by platelets in diseased or damaged blood vessels (see Figure 1). While aspirin has been the primary antiplatelet agent, over the past ten years, ticlopidine (Ticlid), clopidogrel (Plavix) and extended release dipyridamole plus aspirin (Aggrenox) have been approved for use in this setting.

Cyclooxygenase Inhibitors and Cardiovascular Disease

A study published in the Journal of the American Medical Association has raised the question of whether the use of selective cyclooxygenase-2 (Cox-2) inhibitors might be associated with an increased incidence of cardiovascular events.

Cox-2 selective inhibitors were developed in an attempt to reduce the adverse gastrointestinal events associated with the use of traditional, non-specific non-steroidal anti-inflammatories (NSAIDs). This was based on the premise that Cox-1 predominates in the gastric mucosa and yields protective prostaglandins, whereas Cox-2 is induced in inflammation and leads to pain, swelling and discomfort. However, selective Cox-2 inhibitors are known to decrease vascular prostacyclin (PGI2) production and may affect the balance between prothrombotic and antithrombotic eicosanoids, perhaps leading to increased cardiovascular thrombotic events. Cox-1 inhibitors afford a measure of platelet inhibition that reduces this effect.

A recent meta-analysis suggests that there may be an increase in cardiovascular events in patients taking Cox-2 inhibitors relative to those taking traditional, non-specific NSAIDs. The researchers analyzed the rates of cardiovacular events occurring in participants in 4 trials: the VIGOR trial, the CLASS study, and Study 085 and Study 090, submitted to the US Food and Drug administration.

The study suggested that patients taking rofecoxib had a relative risk of 2.38 (p<0.001) for developing a cardiovascular event when compared to those taking the traditional NSAID, naproxen. In contrast, the analysis of patients taking celecoxib as compared to ibuprofen or diclofenac did not show the same results--there was no significant increase in cardiovascular events in this group.

There are many caveats to the study and critics have pointed out major flaws in the analysis. The differences in the rates of cardiovascular events between patients taking rofecoxib and those taking naproxen may result from a number of factors. Most of the patients involved in the VIGOR study suffered from rheumatoid arthritis, a condition known to predispose patients to a higher risk for MI. Further analysis is required in a more representative sampling of patients. In addition, the trials analyzed in this study focused solely on continuous use of Cox-2 inhibitors and did not examine the more common method of using the drugs sporadically for musculoskeletal pain.

Finally, it remains to be determined whether the higher rate of cardiovascular events associated with rofecoxib relative to naproxen results from a negative impact of rofecoxib or from a positive impact of naproxen on platelet inhibition. This result would more readily explain the lack of difference in cardiovascular events seen with the CLASS study comparing celecoxib to ibuprofen and diclofenac, two NSAIDs that do not have the same antiplatelet effects as naproxen.

Source

1. Mukherjee D, Nissen SE, Topol EJ. Risk of cardiovascular events associated with selective Cox-2 inhibitors. JAMA. 2001:286:954-9.

Perindopril for Stroke?

A familiar drug may have previously unrealized benefits for stroke patients. Results from a landmark six year study of more than 6,000 patients were presented at the European Society of Hypertension (ESH) Congress meeting in Milan earlier this year. The study, 'PROGRESS' (Perinodopril prOtection aGainst REcurrent Stroke Study), was designed to provide evidence regarding the balance of benefits and risks conferred by blood pressure lowering with a perindopril (Coversyl) based regimen among patients with a history of stroke or transient ischemic attack (TIA).

Fifty-eight percent of patients in the study were given perindopril (4 mg) and the diuretic indapamide (Lozide) (2.5 mg) or a placebo daily, and the remaining patients were given perindopril (4 mg) alone or a placebo daily. Participants in the study were free to take any other medications prescribed by their physicians, including other hypertension medications.

Results showed that the ACE inhibitor, perindopril, reduces the incidence of recurrent stroke by 28% compared to placebo; this decrease in stroke rates was seen in both hypertensive and normotensive patients. After an average follow-up of four years, the treatment groups had 50% fewer hemorrhagic strokes overall and 24% fewer ischemic strokes than did the placebo group. In addition, rates of non-fatal MI and dementia due to stroke were both reduced by 38% and 34% respectively in the treatment groups when compared to placebo. Severe cognitive decline due to stroke was reduced by 45%.

World health statistics indicate that about five million people die from stroke every year and at least 15 million others suffer non-fatal strokes that are frequently disabling. About one in five survivors will suffer another stroke or heart attack within five years.

Drug Use in Nursing Homes: Legislating for Quality

Carmel M. Hughes, PhD
Senior Lecturer in Primary Care,
Pharmacy and National Primary Care Career Scientist,
School of Pharmacy,
The Queen's University of Belfast,
Northern Ireland.

Populations in the developed world are aging and the greatest demographic change is seen in those over the age of 80 years. Although it is a remarkable achievement in human survival, this demographic shift does present major challenges to health policy makers and providers. Health care for older people will need to be delivered at many levels--i.e., acute, intermediate, residential and home settings. The long-term care sector (nursing and residential homes) represents one area that can expect to face greater demands for delivery of quality services.

Quality of care and its assessment have become major concerns in most health markets in the developed world and long-term care is no exception. Perhaps the best system for assessing quality exists in the United States (US). This paper will provide an overview of the approach taken in US nursing homes with respect to drug use and contrast this with strategies in other countries.

Legislating for better care: the US situation
In 1983, the US Congress asked the Institute of Medicine to make recommendations for improving the quality of care in nursing homes.¹ The report, published in 1986,2 revealed substantial evidence of appallingly bad care in many nursing homes in the USA.

Pharmacological Agents for Unintentional Weight Loss in Older Adults: A Review

David R. Thomas, MD, FACP, FAGS
John E. Morley, MB, ChB
Division of Geriatric Medicine
Saint Louis University Health Sciences Center and
GRECC, Veterans Administration Center
Saint Louis, MO, USA.

Abstract
Unintentional weight loss is a common problem among older adults, especially those in institutional settings. Physicians respond by prescribing increased oral calories, prescribing nutritional supplements or by considering enteral feeding. The response of patients to these interventions is often poor. For this reason, pharmacological agents that stimulate appetite or produce weight gain have attracted considerable attention. Should these agents be used? This review focuses on the benefits and risks of these orexigenic agents.

Introduction
Malnutrition is a major problem among residents in long-term care facilities.^1-4 The prevalence of protein-energy malnutrition in nursing home residents ranges from 23-85%.5,6 By comparison, the prevalence of protein-energy malnutrition ranges from 32-50% in acutely hospitalized patients.^7,8 The high prevalence of malnutrition in nursing homes may reflect a unique problem in elderly persons, the presence of chronic conditions, failure to address specific nutritional problems in this setting, or transfer of malnourished patients from acute care hospitals to long-term care facilities following an acute illness.

What Physicians Should Know about Herbal Medicines.

Potential Herb-Drug Interactions in Older People

Julie Dergal, MSc
Kunin-Lunenfeld Applied Research Unit,
Baycrest Centre for Geriatric Care,
Toronto, ON.

Paula A. Rochon, MD, MPH, FRCPC
Baycrest Centre for Geriatric Care,
Assistant Professor of Medicine,
University of Toronto, Toronto, ON.

Introduction
The use of herbal medicines has recently gained a great deal of acceptance in North America. In 1996 in the United States, an estimated two billion dollars was spent on herbs, tablets, extracts, capsules, and teas, in health food stores.¹ In 1997, Eisenberg conducted a telephone survey of 2055 people and found that 12% used herbal medicines, a 4-fold increase from 1991.² Despite the widespread use of herbal medicines in North America, little research has examined the safety of these alternative medicines, particularly when taken in conjunction with conventional medicines. A common misconception about alternative medicines is that they are "natural" and are, therefore, safe. However, herbal medicines are marketed as dietary supplements and, as such, are not subject to the rigorous standards established for conventional drug therapies. This means that the quality and content of herbal medicines are largely unregulated and uncontrolled.

Safety Concerns with Colon Cancer Drug

The Mayo Clinic has reported that patients taking a commonly prescribed treatment for colon cancer are dying at almost three times the rate of patients who took other medications for the same disease. The chemotherapy drug, irinotecan, has been shown to increase life expectancy by about two months for patients with advanced colorectal cancer. However, in the first two months of receiving the drug, 33 out of 1,199 patients died, among patients taking different drugs, only 10 out of 905 patients died within the same period.

The drug is manufactured by Pharmacia and marketed under the name Camptosar. Although the findings are preliminary and not statistically significant, the company has sent letters to doctors in the US advising them of the results. The finding is somewhat controversial, as this effect of the drug has not been seen previously. However, the research group at the Mayo Clinic explains that this may result from the fact that the deaths were spread out among different medical centres, and when data were pooled the effect was seen; it might not have been obvious to individual physicians. Doctors who are conducting the study will be giving the drug in lower doses and will be more aggressive about looking for warning signs of toxicity, including diarrhea, nausea, vomiting and a low white blood cell count.

The results of the study will be published in a letter in an upcoming issue of the New England Journal of Medicine.