Miacalcin: A New Drug Option for Treating Established Osteoporosis

Anna Liachenko, BSc, MSc

Canadian postmenopausal women now have a new drug option for treatment of established osteoporosis and/or relief of pain associated with osteoporotic fractures--synthetic salmon calcitonin administered as a nasal spray (Miacalcin Nasal Spray or Miacalcin NS). Already available in over 70 countries, the drug was approved in Canada in September of 1999. The nasal spray is very safe and has been shown in various studies to increase bone mineral density (BMD) in vertebrae, the primary site of fractures in postmenopausal osteoporosis. Several months ago a large clinical trial confirmed that Miacalcin NS lowers the risk of vertebral fractures, making it an important agent for osteoporotic therapy.⁶

Calcitonin is a peptide hormone secreted by the thyroid gland and its secretion is under the direct control of blood calcium levels. In humans, no definite effects on calcium levels are seen in states of calcitonin deficiency or excess. Calcitonin was discovered over 35 years ago by Dr. Harold Copp at the University of British Columbia. Secretion calcitonin is estrogen-dependent and is decreased after menopause.^7,8 Osteoporotics have lower levels of serum calcitonin than both premenopausal and healthy menopausal females. It is likely that the deficiency in the hormone plays some role in postmenopausal bone loss, and studies have found that calcitonin counteracts both early and established osteoporosis.

Antitelomere Agents A Promising Cancer Therapy

Antitelomere Agents A promising Cancer Therapy

A group of scientists have identified a family of compounds that inhibit telomerase, leading to death of cancer-like cells in vitro. Dr. B.S. Hurbet and colleagues report that peptide nucleic acid and 2'-0-MeRNA oligomers inhibit telomerase, leading to telomere shortening, and causing immortal cells to undergo apoptosis with increasing frequency. These cells were able to regain their original telomere length after the therapy was stopped which suggests that the side effects of antitelomerase agents might be minimal. However, this also implies that continuous administration of the drug will be necessary to prevent telomere re-growth in cancerous cells.

These agents could potentially be used to treat cancer in combination with other chemotherapy agents. The combination therapy is necessary because it takes a substantial period of time before antitelomere agents start to have effect on cancerous cells. Similar compounds are already being tested for conditions other than cancer. The researchers report that it should be possible to test these agents in both animals and humans in the near future.

Source: Proceedings of the National Academy of Science 1999;96:14276-14281.

Relenza: The New Inhalant Neuraminidase Inhibitor for Influenza

D'Arcy L. Little MD, CCFP
York Community Services, Toronto

Relenza (zanamivir), an orally-inhaled anti-viral medication effective against all known strains of the influenza virus, was approved by the Therapeutic Products Program of Health Canada on November 3, 1999.

Epidemiology
It is estimated that in Canada influenza affects between 10 to 15% of the population (between 3 and 5 million people) each year. The number of affected persons can be as high as 80% of nursing home residents. In addition, these infections result in about 75,000 hospitalizations and 7,000 deaths yearly.¹ In economic terms, flu-related costs to the Canadian economy during the 1997-98 flu season were estimated to be over $1 billion.²

The Mainstay of Treatment for Influenza
The influenza vaccine has been and remains the mainstay of prophylactic protection against influenza, and is recommended for elderly and high-risk patients, their household contacts, and health-care personnel. Under ideal circumstances, in healthy, young adults, vaccine effectiveness is in the range of 70-90%, with much lower effectiveness in the elderly (30-50%).³ For optimal results, it is recommended as a single 0.5 ml IM dose to be given from October through mid-November, although it can be given from September to the end of the influenza season.

Is There a Role for Thrombolytic Therapy in the Management of Acute Ischemic Stroke?

Joyce So, BSc

While thrombolytic therapy has become an established part of treatment for acute ischemic heart disease, the controversy continues regarding its potential and practical use in acute ischemic stroke. In a situation where time is of the essence, is thrombolysis the best available solution?

Acute ischemic stroke (AIS), or "brain infarction", is most commonly a result of intracerebral artery occlusion due to embolism from proximal sites such as the internal carotid arteries, heart or aorta. Unlike cardiac arrest, where brain viability is measured in minutes, AIS presents with a mixture of salvageable tissue, allowing for a therapeutic window that can last several hours. While the definitive time frame has yet to be pinned down, the generally accepted mantra "Time is Brain" reflects the notion that prognosis is improved by early intervention. The question now is whether there is a role for thrombolytic therapy in the management of AIS.

The two most prominent candidates for use in thrombolytic AIS therapy are streptokinase and recombinant tissue plasminogen activator (rtPA), both serine proteases that catalyze the conversion of plasminogen to plasmin, which digests fibrin clots.

Secondary Prevention of Stroke: The Role of Antiplatelet and Anticoagulant Agents

D'Arcy L. Little, MD, CCFP
York Community Services, Toronto, ON

Introduction
Every year there are approximately 50,000 strokes in Canada. Currently, close to 300,000 Canadians are stroke survivors. As stroke is an age-related condition, the number of strokes is predicted to increase as the Canadian population ages. The resultant national cost, which is estimated at 2.7 billion annually, will also increase unless improvements are made to prevention and treatment.¹ Approximately 1 in 6 survivors of a first stroke experiences a recurrent stroke over the next 5 years, of which 25% are fatal within 28 days.² The above statistics suggest that attention to secondary stroke prevention would be important in reducing the morbidity, mortality and cost to society of stroke. The purpose of this article is to review the role of anti-platelet and anticoagulant agents in the secondary prevention of stroke.

Goals of Therapy
Therapeutic measures in secondary stroke prevention aim to prevent recurrent stroke or transient ischemic attacks, with the aim of preventing morbidity and mortality from incremental neurological deficits, as well as preventing associated cardiac ischemic events.

The Future of Diabetic Care: Non-invasive Glucose Monitors, Insulin Puffers, and Vaccines

Lilia Malkin, BSc

Diabetes mellitus (DM) is estimated to affect approximately 1.5 million Canadians and 135 million people worldwide.^1,2 This article will review some of the recent advances in diabetes care and prevention, including non-invasive glucose monitoring, insulin delivery systems and "vaccination" to prevent the development of type I DM.

Maintenance of a physiologically appropriate blood glucose (BG) level is an essential component of diabetes control, as it has been shown to play an important role in reducing the debilitating sequellae of DM.^3,4 For many patients, good diabetes control may involve not only carefully planned meals, appropriate exercise regimens, and oral medications, but also interventions that may be invasive and painful, such as frequent BG monitoring and insulin injections. Decreasing or eliminating the discomfort associated with some of the more invasive procedures is likely to increase patients' compliance with therapeutic regimens, resulting in improved control of the disease.

The recent advent of minimally- and non-invasive BG monitors has the potential to replace, or at least decrease the use of the traditional "finger-prick" apparatus for the multitude of patients who require self-monitoring of BG levels.

New Drug Offers Hope for Optimizing Glycemic Control

Sheldon Singh, BSc
Toronto, ON and

George Fantus, MD, FRCPC,
Diabetology
Mount Sinai Hospital
Toronto, ON and
Director, Banting & Best Diabetes Centre Core Lab

In the USA, the prevalence of type 2 Diabetus Mellitus (T2DM), in individuals over 65 is estimated to be 10%. This is twice the prevalence of the overall USA population. The worldwide prevalence of T2DM is steadily increasing due to factors such as an increase in the elderly population, obesity, and decreased physical activity.

Multiple mechanisms are involved in the pathogenesis of T2DM including impaired insulin secretion by pancreatic b-cells, increased hepatic gluconeogenesis, and reduced glucose uptake by muscles and adipose tissue (see figure 1). These factors lead to hyperglycemia and in the long term, micro- and macrovascular complications. Available evidence indicates that improved glycemic control will decrease the complications of diabetes; this may be achieved with a combination of dietary, exercise and pharmacologic interventions.

Current pharmacologic agents used to treat T2DM include sulphonylureas (glibenclamide, gliclazide), biguanides (metformin), alpha-glucosidase inhibitors (acarbose), or insulin.

Public Coverage of Donepezil Achieved in Two Provinces

Eleanor Brownridge

Until recently, many general practitioners have been hesitant to diagnose Alzheimer's Disease (AD), especially at the mild and moderate stages. They believe that patients and their families don't want to hear this bad news and therefore don't push the issue.

"We have to work hard to change the attitudes of physicians," says Dr. Ron Keren, geriatric psychiatrist with the University Health Network, Toronto General Hospital. "We have to move away from stigmatizing Alzheimer's and start approaching it as any other serious disease. We need to talk frankly, openly and honestly with our patients." Research from the United States has shown that 80 percent of seniors want to know if they have dementia. Dr. Keren, who also practices at the Toronto Rehabilitation Institute and the Whitby Health Centre, says that in over seven years he has never had a patient who didn't want to know the state of his disease. "If you can't talk about it, how can you treat it?"

With the recent decisions of Ontario and Manitoba to reimburse donepezil (Aricept) in those provinces, physicians now have a treatment for mild to moderate dementia of the Alzheimer's type that can bring hope to all patients and their families, not just those who can afford it.

Donepezil inhibits the activity of acetylcholinesterase, thereby increasing levels of acetylcholine in the brain.

No More Splitting Pills

No More Splitting Pills! Study Calls for Low Dose Pills for Seniors

An Ontario study is calling for pharmaceutical companies to make low dose tablets of commonly prescribed drugs for seniors.

The population-based study, conducted by Baycrest Centre for Geriatric Care, was published in the August issue of the Journal of the American Geriatrics Society. It is the first comprehensive look at low dose prescribing in a large population of seniors.

Using the Ontario Drug Benefit Plan database, investigators at Baycrest identified over 133,000 adults aged 65 and older who were prescribed either thiazide diuretics or beta blockers over a one-year period from 1995 to 1996.

The study found that of the 120,000 seniors in Ontario who were repeat users of thiazide diuretics, more than a quarter (26%) were dispensed a dose lower than the standard pills produced by pharmaceutical companies.

The "mismatch" between dosage prescribing and dosage formulations means doctors rely on patients and pharmacists to split standard dose tablets. Splitting pills, particularly when done by older patients who may have impaired vision or motor skills, may increase drug error or lead to frustration and non-compliance.

Theophylline Recommended as an Add-on Therapy for Chronic Lung Disease

Anna Liachenko, BSc, MSc

The popularity of theophylline, a bronchodilator used in the treatment of asthma and other bronchospastic diseases for over 60 years, has been declining due to its narrow therapeutic index and the perceived lack of anti-inflammatory effects. Instead, newer therapies, such as inhaled long-acting corticosteroids, have been increasingly recommended. Although valued for their anti-inflammatory properties, these newer therapies can nevertheless produce serious side effects at therapeutic concentrations. Fortunately, the prescribed dosages can be decreased due to the recently discovered anti-inflammatory properties of theophylline, which is now recommended as an add-on therapy to corticosteroids. In this article, the beneficial effects and necessary precautions when using theophylline are examined, with particular emphasis on the elderly.

In Canada, theophylline is currently indicated for the symptomatic treatment of reversible bronchospasm associated with asthma, chronic bronchitis, emphysema, and associated bronchospastic disorders. Historically, asthma was treated mainly with bronchodilators. During the 1980s it became apparent that an unacceptably high rate of asthma-related hospitalizations and asthma deaths were partly attributed to the under-use of anti-inflammatory medications. For this reason, the use of inhaled corticosteroids increased. Unfortunately, there is some systemic absorption of inhaled corticosteroids.