Antiglutamate Agents Hold Promise for Control of Hallucinations in PD

Interview with Dr. Michel Panisset

Dr. Michel Panisset is the Director of the Movement Disorder Clinic at the McGill Centre for Studies in Aging, and an Assistant Professor in the Department of Neurology and Neurosurgery at McGill University. He specializes in neurology and movement disorders and is particularly interested in Parkinson's Disease. He is also a member of the Parkinson Study Group. Dr. Panisset kindly agreed to share his knowledge and views on the best methods to control hallucinations in patients suffering from PD.

Q: Do hallucinations constitute a big problem for your patients who suffer from Parkinson's disease? How do these hallucinations affect a patient's wellbeing and daily functioning? Do they affect a patient's compliance with medication?

A: Approximately 20 to 40% of patients with Parkinson's Disease experience hallucinations. When we look at our own data, we find that this number is closer to 40%. So, it is a very significant problem. Hallucinations usually start in patients suffering from a more advanced stage of the disease, who have greater problems with cognition and require more medications. We do not see a strong effect on compliance in this particular subpopulation of patients. Typically, when a patient suffers from cognitive or psychiatric problems, medications are administered with the help of a caregiver.

Movement Disorders: A Potentially Dangerous Outcome of Specific Classes of Drugs

Nadège Chéry, PhD
Medical Writer/Consultant,
Snell Medical Communication Inc.
Montreal, Qc

The prescription of medications is among the most frequent and the most reliable forms of therapeutic strategy that physicians use for the treatment of patients with a variety of medical disorders.¹ Unfortunately, many of these medications also produce side effects, especially in the geriatric population,¹ some of which may be mild and relatively tolerable by most patients, and others, such as dyskinetic reactions, which are considered harmful.^2,10 Drug-induced movement disorders represent an important iatrogenic condition that is occasionally encountered in clinical practice.² These potentially disabling movement disorders are involuntary, they appear to be idiosyncratic extensions of the expected action of the drug and they are known to particularly affect the elderly patient.^2-6 Among the devastating consequences of these disorders are involuntary movements, which may contribute to falls and fractures in the elderly, and social isolation, which can result from the limited mobility of an elderly individual.^4,7

Nonetheless, movement disorders are often reversible; the withdrawal of the offending drug(s) usually leads to the alleviation of symptoms.³ Unfortunately, in some cases, discontinuing the offending drug may not be feasible.

Manipulation of Dopaminergic Pathways is Mainstay of Pharmacological Treatment of PD

The history of the use of pharmaceuticals to alleviate the symptoms of Parkinson's disease (PD) began 125 years ago, when belladonna alkaloids were first used in an attempt to control severe drooling in patients suffering from PD. These alkaloids possess anticholinergic activity, and unexpectedly, they alleviated other characteristic symptoms of PD, which include tremor, rigidity, akinesia and postural instability. However, it was not until 1958 that researchers discovered the presence of high levels of dopamine in the striatum of the brain and showed that the dopamine precursor (levodopa or L-dopa) reversed the tranquillization and parkinsonian-like motor impairments induced by treatment with reserpine. This set the stage for the development of the first real pharmacotherapy for treatment of PD.

Sanjiv CC, DM,
Tsui JKC, MD, FRCPC
Neurodegenerative Disorders Centre,
University of British Columbia,
Vancouver, BC, Canada

Dopaminergic Agents
At present, there is no pharmacological cure for Parkinson's disease (PD) and only the symptoms of the disease can be treated. There is no firm evidence to support the notion that any drug has a neuroprotective action in PD; therefore, the mainstay of current drug therapy is the manipulation of the dopaminergic pathways.

Levodopa (L-DOPA)
L-dopa is the most commonly prescribed medication for the treatment of PD.

Intramuscular Form of Atypical Antipsychotic Announced

Anna Liachenko, BSc, MSc
Managing Editor,
Geriatrics & Aging

Due to a favourable side effect profile and high efficacy when compared with typical antipsychotics, atypical drugs are becoming increasingly recommended as first-line treatments for agitation and psychosis related to schizophrenia, manic depression, and behavioural disturbances associated with dementia. At the recent XXII International Congress of Neuro- psychopharmacology (CINP) in Brussels, a new study evaluating an intramuscular (IM) form of Olanzapine (Zyprexa) was presented. An IM form of antipsychotics can be crucial for the rapid control of a patient's psychotic symptoms in an emergency setting. This is the first time that an atypical antipsychotic is available in IM form. The study has just been completed and will be published shortly. Dr. Karena Meehan, M.D., clinical research physician for Eli Lilly and Company and the lead physician for the IM project with responsibility for the Canadian and American groups, agreed to answer a few questions about recent studies on Olanzapine and the use of this drug in the elderly.

Q: Your group has recently presented data comparing the effect of a new IM-formulation of the antipsychotic olanzapine with IM-haloperidol. What were the objectives and the results of your study?

A: The study was designed to compare olanzapine with an older typical antipsychotic.

Pharmaceutical Management of Glaucoma

Reviewing the Major Classes of Antiglaucoma Medication

Catherine M. Birt, MA, MD, FRCSC
Sunnybrook & Women's College
Health Science Centre,
Assistant Professor,
University of Toronto

Medical management of glaucoma is a field that has expanded dramatically over the past five or six years. Since aging is one of the major risk factors for the development of glaucoma, it is an area that is of great relevance to anyone managing geriatric patients. The purpose of this article is to review the five major classes of antiglaucoma medications, the drugs that are currently available in each class, their indications and their side effects.

Glaucoma is considered to be an optic neuropathy with characteristic optic nerve damage (with loss of the neuroretinal rim and an increased cup-to-disc ratio) and visual field changes (with arcuate field defects progressing to complete loss of peripheral vision). Intraocular pressure (IOP) is not part of the definition of the disease, as many people with statistically elevated IOP do not develop the neuropathy, and many patients with statistically normal IOP do. Intraocular pressure is considered a major risk factor for the development of glaucoma. Other risk factors include advanced age, race, positive family history, myopia, and systemic factors such as diabetes and hypertension. Glaucoma is generally divided into open versus closed angle, and each of these can be subdivided into primary and secondary subtypes.

What is Better for my Elderly Cardiovascular Patient, Surgery or Pharmaceutical Intervention

Kimby N. Barton, MSc
Assistant Editor,
Geriatrics & Aging

With recent advances in medical interventions for the treatment of cardiovascular diseases, including the introduction of ACE inhibitors and the use of b-blockers for left ventricular dysfunction, the role of coronary revascularization in managing elderly cardiovascular patients has become more difficult to define. Unfortunately, the bulk of research in this area has either failed to compare treatments directly, or has excluded patients who are 65 years or older. Research in this field has also focussed on long-term benefits of surgery over medical treatment, which may not be as germane to an elderly patient as symptomatic improvements, given that this patient's life expectancy may be considerably shorter than that of someone younger. In addition, with the increased frailty that accompanies old age, perioperative mortality and postoperative complications are a much greater concern for elderly patients. They are at an increased risk for stroke, acute renal failure, and other major complications. All of these factors suggest that caution should be exercised when extrapolating data from younger patients and applying it to older ones.

Therapeutic Approaches for Treatment of Alzheimer’s Disease

Reviewing the Benefits and Limitations of Psychotropics and Cholinesterase Inhibitors

Wafa Harrouk, PharmD

The following are brief summaries of salient points from presentations in the session on Therapeutic Approaches for the Treatment of Alzheimer's disease, Sunday July 9th, 2000.

Clinical Status of Therapy for Behavioral Disturbances
Dr. Jeffrey L. Cummings, MD, from the Alzheimer's Disease Center, University of California, highlighted some of the most salient therapeutic interventions that are currently available for treatment of behavioural disturbances associated with AD. Alzheimer's disease (AD) is associated with a variety of neuro-psychiatric disturbances, including delusions, hallucinations, anxiety, depression, apathy, irritability, disinhibition, and agitation. Patients may also suffer from aberrant motor behaviours such as rummaging, pacing and wandering. These behavioural disturbances are stressful to the patient as well as to their caregivers. Appropriate treatment of these disturbances would improve the patients' quality of life, alleviate their caregiver's stress, and delay their placement in a nursing home. Relatively few double blind, placebo control trials of psychotrophic medications have been conducted on patients with AD.

Why Shingles Occurs Mostly in Seniors

Gradual Immunologic Decline Explains Frequency of Herpes Zoster Among the Elderly

John M Conly, MD,CCFP, FRCPC, FACP
Consultant, Infectious Diseases
Director, Infection Prevention and Control
University Health Network (Toronto General,
Toronto Western and Princess Margaret Hospitals)
Professor of Medicine, University of Toronto

Introduction
Although it is now understood that varicella-zoster virus (VZV) is the etiologic agent for both varicella and herpes zoster, it is of historical interest to note that in the early medical literature, the clinical illnesses of varicella and herpes zoster were considered separate entities. Just six decades ago it was still taught at Harvard University that these viruses were unrelated.¹ In 1943, a pediatrician named Garland suggested that zoster may be due to the reactivation of a latent varicella virus,2 but it was not until 1958 that VZV was definitively recognized as the etiologic agent for both varicella and zoster.^3,4 The VZ virus is a DNA virus and is a member of the Herpesviridae family bearing many distinct similarities to other members of this group of viruses. The virus is spread by direct contact, by droplet and airborne routes from vesicular fluid of skin lesions, or from secretions from the respiratory tract.⁵ Transplacental transmission has also been documented.

Too Many Pills Can Cause Life-threatening Spills

Psychotropic Drugs and Polypharmacy are Proven Risk Factors for Falls

Tawfic Nessim Abu-Zahra, MSc

Many risk factors have been shown to contribute to falls suffered by the elderly, including the use of sedatives¹ and the concurrent use of several medications.^2-4 Evidence-based conclusions concerning the relationship between drugs and falls provide limited confirmation due to the studies results' variability, inconsistencies in classification schemes of drugs, and because of the small number of subjects participating in most studies.³ Thus, singling out specific agents and recommending guidelines for prescribing to the elderly is difficult. However, some studies have implicated psychotropic or CNS-active drugs, including sedatives, antidepressants and neuroleptics, as being especially high-risk in terms of leading to falls. Hence, special caution should be taken in prescribing these for the elderly.

Leipzig and colleagues reviewed^3,4 all existing literature dealing with the association between drugs and falling in the elderly. Pooled odds ratios that measure the likelihood that a person taking a drug will also experience a fall were calculated for different classes of drugs.

Genetics of Drug Metabolism: The Beginnings of Individualized Medicine for the Elderly

Lilia Malkin, BSc

Throughout the centuries, people have turned to medicinal substances to improve their health and quality of life. Today, medi-cations continue to be invaluable partners in humanity's war against disease. However, each person has a unique response to his or her medication(s). The differences among patients' reactions to pharmaceutical therapy can be at least partially explained by the inter-individual variation in drug metabolism. As biotechnology continues to make progress, the genetic foundation for illness and the consequent response to treatment is becoming increasingly apparent.^1,2 The basis for patient-to-patient variability in the effects of pharmaceutical agents has thus far been attributed predominantly to the drug-metabolizing capacity of the liver.¹ Accordingly, this article will focus on the hepatic biotransformation enzymes and the contribution of genetic polymorphism to individuals' thera-peutic responses and to treatment-related complications. It should be noted that tissue receptors and transporter proteins are also often subject to polymorphic variations, contributing to the variable response to medications and toxins; a discussion of this topic is, however, beyond the scope of this paper.

Hepatic Drug Metabolism Enzymes: An Overview
The metabolism and elimination of pharmaceutical agents may occur at several sites in the human body, including the liver, kidneys, gastrointestinal (GI) tract, lungs, and skin.