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Drug Safety

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Ezetimibe and the Treatment of Dyslipoproteinemia

Lucie Lavoie, MD, FRCP(C), Resident in Geriatrics, Faculty of Medicine, Université Laval, Quebec City, QC.
Claude Gagné, MD, Service of Lipidology, Department of Medicine, Université Laval, Quebec City, QC.

Complications of coronary artery disease are the leading causes of morbidity and mortality in older persons of both sexes. The control of risk factors may prevent, retard and reverse the evolution of atherosclerosis in older adults, as in younger persons. Thus, treatment of hypercholesterolemia should not be negated on the pretext of age. In addition to non-pharmacological approaches, pharmacological tools are available. Recently, ezetimibe, an inhibitor of intestinal cholesterol absorption, has been launched. We will discuss the usefulness and the potential place of this medication for the treatment of hypercholesterolemia in the older population.
Key words: cholesterol absorption inhibitor, ezetimibe, dyslipidemia, atherosclerosis.

Related Terms: Drug Safety, atherosclerosis, cholesterol absorption inhibitor, dyslipidemia, ezetimibe

The Biologic Treatments for Inflammatory Arthritis: Is There a Role in the Elderly

Francis S. W. Zih, BSc, Research Associate and Mary-Ann Fitzcharles, MB, ChB, FRCP(C), Associate Professor, Division of Rheumatology and McGill-MGH Pain Centre, McGill University and McGill University Health Centre, Montreal, QC.

The inflammatory polyarthritides take a huge toll on the well-being of an individual. The ability to specifically target inflammatory molecules with the new "biologic" treatments has been an outstanding laboratory development that has rapidly entered the clinical domain. Early experience in the use of these costly agents has shown an excellent clinical response with both alleviation of symptoms and slowing of disease progression. There is, however, concern regarding the emergence of adverse effects. The side effect of both chronic and bacterial infections, likely more prevalent in the elderly, requires caution and meticulous patient care. Until more is known about the long-term use regarding both continued efficacy and side effects, these treatments currently should be offered to patients with the most severe and poorly responsive disease.
Key words: inflammatory arthritis, disease modifiers, biologics, infectious complications.

Related Terms: Drug Safety, biologic agents, disease modifiers, infectious complications, inflammatory arthritis

Relationship Between Antidepressants and the Risk of Falls

Barbara Liu, MD, FRCPC, Sunnybrook &Women's College Health Sciences Centre and the Kunin-Lunenfeld Applied Research Unit, Baycrest Centre, Toronto, ON.

Falls are a common problem among older patients. Medications in general, and psychotropic drugs in particular, have been shown to increase the risk of falls. The possible mechanisms whereby psychotropic drugs increase this risk include sedation, orthostatic hypotension, arrhythmias, confusion due to anticholinergic effects, and dopaminergic effects on balance and motor control. Several epidemiological studies have identified antidepressant use--both tricyclic and selective serotonin re-uptake inhibitors--as a risk factor for falls. When treating a patient with an antidepressant, efforts should be made to reduce other modifiable risk factors for falls by optimizing intrinsic and extrinsic risk factors for falls.
Key words: falls, antidepressant, hip fracture, tricyclic antidepressant, selective serotonin re-uptake inhibitor.

Related Terms: Drug Safety, Falls and Fitness, antidepressants, falls, hip fracture, selective serotonin re-uptake inhibitor, tricyclic antidepressant

Drug Treatment for Neuropathic Pain in the Elderly

D'Arcy Little, MD, CCFP, Director of Medical Education, York Community Services; Lecturer and Academic Fellow, Department of Family and Community Medicine, University of Toronto; 2002-3 Royal Canadian Legion Fellow in Care of the Elderly, Toronto, ON.

Neuropathic pain is a relatively common and challenging entity in the elderly, with a wide differential diagnosis and numerous treatments available. In general, damage to peripheral nerves via an injury or as a result of abnormal functioning is thought to trigger a cascade of events in sensory neurons that is responsible for the generation of pain. Potential treatments include tricyclic antidepressants, serotonin re-uptake inhibitors, venlafaxine, ion channel blockers, opioids, capsaicin and the Lidocaine patch. This article reviews the relative efficacy of these treatments, with specific reference to considerations in the elderly.
Key words: neuropathic pain, peripheral neuropathy, treatment, anticonvulsant, antidepressant.

Related Terms: Drug Safety, anticonvulsant, antidepressants, neuropathic pain, peripheral neuropathy, treatment

Possible Polypharmacy Perils Await Elderly

Dr. Clarfield is the Chief of Geriatrics, Soroka Hospital Centre, Professor, Faculty of Medicine, Ben Gurion University of the Negev, Beersheva, Israel, and Professor (Adjunct), Division of Geriatric Medicine, McGill University, and Jewish General Hospital, Montreal, QC.

The other day, I was consulted on a 75-year-old lady who was (supposedly) ingesting 12 different medications: ranging across the daylight hours and in all the colours of the spectrum, exhibiting various shapes and sizes. Some were to be taken before, others after, and the remainder with meals. The total number of tablets that was theoretically being consumed by this lady was 62. Individually, all of these medications could have caused adverse drug reactions (ADR), and many of them are also known to interact in various ways with each other. My patient exhibited a typical "final common pathway" of the results of basic research, drug trials, pharmaceutical marketing, physician prescribing practices and pharmacist dispensing behaviour. Unfortunately for the patient in question, the option of noncompliance was not available since her husband tried his best to help her ingest this immense pharmacological load.

This lady represents an extreme example of the kind of medication problems that elderly patients can face in Canada. Yet, it must also be pointed out that the modern pharmaceutical armamentarium is more extensive and far superior to that available 30 years ago.

Related Terms: Drug Safety, polypharmacy

The Use of Traditional and New Anticoagulants in the Elderly

Anne Grand'Maison, MD, FRCPC, Hematologist, Research Fellow, Thromboembolism Department, Sunnybrook and Women's College Health Sciences Centre; University of Toronto, Toronto, ON.
William Geerts, MD, FRCPC, Consultant in Clinical Thromboembolism, Sunnybrook and Women's College Health Sciences Centre; University of Toronto, Toronto, ON.

The elderly population is at risk of arterial and venous thromboembolic diseases. Traditional anticoagulants have demonstrated their benefits for prevention and treatment of these conditions and are accepted as standard practice. Despite this evidence, anticoagulants are still underused in older people. Practitioners often hesitate to consider anticoagulation in the elderly because of comorbidities, potential drug interactions and increased risk of bleeding. Careful assessment of bleeding risk and close monitoring of anticoagulant level are essential strategies to optimize the use of anticoagulants in the elderly. Many recently developed antithrombotics that have completed late stage of testing are presented in this review, although further studies are needed to determine their exact role, particularly in the elderly.
Key words: factor Xa inhibitor, antithrombin, renal insufficiency, drug interactions, bleeding risk index.

Related Terms: Drug Safety, antithrombin, bleeding risk index, drug interactions, factor-Xa inhibitor, renal insufficiency

Careful Comparison of ACE Inhibitors vs. Diuretics

With the lifelong probability of developing hypertension estimated to be as high as 90%, it is little wonder that each subsequent hypertension treatment trial is met with much media frenzy. The 2002 ALLHAT indication that thiazide-like diuretics were at least as effective as calcium antagonists, ACE inhibitors or alpha-adrenergic blockers in reducing CV events in hypertensive patients made a major impact on physicians and patients alike, casting doubt on the efficacy of new drug classes over old and inexpensive standbys.

Predictably, the ALLHAT conclusions were barely digested when a new and apparently contradictory study appeared in the New England Journal of Medicine. The Second Australian National Blood Pressure Study (ANBP2) examined 6,083 hypertensive subjects aged 65-84 years in a prospective, randomised, open-label trial. The patients were tracked for an average of 4.1 years to determine the benefits of treatment with ACE inhibitors versus diuretics.

The treatment aim was to achieve a systolic blood pressure reduction of at least 20mmHg and a diastolic blood pressure reduction of at least 10mmHg. Blood pressure was recorded annually, and the primary endpoint was all CV events or death from any cause. While the diuretic group experienced greater blood pressure reduction than the ACE inhibitor group at years one and two, by the end of the study blood pressure had been similarly reduced in both groups, indicating that both treatments were equally effective in minimising BP.

In the diuretic group, 736 CV events or deaths from any cause were observed, versus 695 in the ACE inhibitor group, representing an 11% reduction in the total burden of CV events or death from any cause in the ACE inhibitor group. This result was significant for the male patients only, in which a 17% reduction was noted. A further breakdown of the results revealed a 12% reduction for all first CV events in the ACE inhibitor group compared with the diuretic group. There were no significant differences between treatment arms in rates of fatal CV or non-CV events, with the exception of the rate of fatal strokes which was in fact higher in the ACE inhibitor group.

The results of this trial at first seem to oppose those of ALLHAT, but upon closer examination the two trials are not necessarily comparable. Although the same classes of antihypertensives were used in each, the specific agents differed, rendering a general claim about diuretics versus ACE inhibitors inconclusive. The subjects in the ANBP2 also were comparatively healthy to those in ALLHAT.

It is important to remember that ALLHAT was not the first antihypertensive study, and ANBP2 will surely not be the last. The emergence of subsequent trials will inevitably "prove" the superiority of one class of agents over the others, but the bottom line is that different treatments are appropriate for different patients based on unique needs. A patient's history and response should determine the ideal course of therapy, not the latest piece of news that has snared the media's fancy.

Source

  1. Wing LMH, Reid CM, Ryan P, et al. A comparison of outcomes with angiotensin-converting-enzyme inhibitors and diuretics for hypertension in the elderly. N Engl J Med 2003;348:583-92.
Related Terms: Cardio-Cerebrovascular, Drug Safety, ACE inhibitors, diuretics

Treatment of Renovascular and Adrenocortical Hypertension in the Elderly

J. David Spence, MD, FRCPC, Stroke Prevention & Atherosclerosis Research Centre, Robarts Research Institute, London, ON.

Effective treatment of hypertension is even more beneficial in the elderly than in younger patients because the elderly have a higher absolute risk of vascular events. Treating hypertension not only prevents stroke, but also reduces risk of dementia. Effective blood pressure control is based on identifying and treating its physiological cause. Renal hypertension, primary hyperaldosteronism and renal tubular abnormalities such as Liddle's syndrome can be identified by measuring the plasma renin and aldosterone. Most elderly patients require diuretic therapy for control, but most will require additional drugs to achieve the lower targets now supported by evidence.
Key words: hypertension, elderly, adrenocortical, renovascular.

Related Terms: Cardio-Cerebrovascular, Drug Safety, adrenocortical, elderly, hypertension, renovascular

Treatment of Hyperglycemia in the Elderly

A.D. Baines, MD, PhD, FRCPC, Professor, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON.

This article presents a summary of recent recommendations for the diagnosis and treatment of Type 2 diabetes in the elderly. Onset of nephropathy, neuropathy and retinopathy can be slowed by treatment designed to reach realistic target values for fasting plasma glucose and HbA1c. Therapy also should minimize the dangers of hypoglycemia. Hepatic and renal function must be monitored when selecting drugs and dosages. Significant reductions in renal function may be associated with serum creatinine within the normal reference range. A stepwise approach to therapy beginning with diet and exercise and proceeding to single and multidrug treatment is outlined. The mode of action, advantages, disadvantages and contraindications for five groups of hypoglycemic agents are summarized.
Key words: Type 2 diabetes, diagnosis, stepped treatment, oral drugs, elderly.

Related Terms: Diabetes-Endocrine Disorders, Drug Safety, diabetes Type 2, diagnosis, elderly, oral drugs, stepped treatment

Antibiotic Treatment of Community-acquired Pneumonia in Older Adults

Theodore K. Marras, MD, FRCPC, Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, California, USA; Postdoctoral Fellow, Department of Medicine, University of Toronto, Toronto, ON.

Abstract
Community-acquired pneumonia (CAP) is a common disease in the older adult with significant mortality. The following review focuses on the antibiotic management of CAP, with specific reference to the older adult. Common etiologic organisms and organism-specific risk factors that tend to be associated with increasing age are presented. The rationale behind initial empiric antibiotic therapy is discussed and recent guidelines for the selection of empiric antibiotic therapy are compared. A synthesis of guidelines for antibiotic selection and recommendations regarding the switch from parenteral to oral therapy are presented.

Introduction
Community-acquired pneumonia (CAP) is a common infectious disease, the incidence of which is consistently associated with increasing age. The overall incidence of CAP has been reported at 10 to 14 per 1,000 patients per year,1,2 and 30 per 1,000 among those older than 75 years.2,3 Compared with people 60-69 years of age, those 70 years or older had a relative risk of developing CAP of 1.5,4 independent of the additional risk conferred by heart disease and institutionalization.

Related Terms: Drug Safety, antibiotic, community-acquired pneumonia, treatment
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