Polypharmacy
Polypharmacy is the taking of multiple medications for multiple medical problems. My winning patient so far had 24 when I saw him in clinic on Wednesday. If anyone honestly thinks that patients are taking all of those medications, with all of their different schedules (two of this one in the morning, 1 at night; 3 of this one every 8 hours; one-half tab of that other one every day), they’ve got to be kidding themselves. How many of us can reliably even take a course of antibiotics for 10 days?
Prevention is the only solution, people. Eat better, exercise more, stop smoking, and wash your hands. That’ll lead you to a healthier life than any pill.
I’ll second that. I take 2 prescriptions (5 pills/day) for my diabetes and 2 more (3 pills/day) for my blood pressure. I have to put them in those little pill-minder thingies to keep them straight and even then I screw up some times. I could get some combo pills and make this simpler, but I’ve managed to get some of my dosages reduced and I’m working on the rest. I’ll be damned if I’m going to complain to any physician about my arthritis, because I’ve learned that exercise is more effective than any pain medication out there for controlling the pain. It’s easier to remember, too.
Presented by the author at the 2003 New England Forensic Sciences Conference at Colby College:
Polypharmacy: What Cost in Morbidity and Mortality?©
It is common practice in Medicine/Psychiatry to put patients on combinations of drugs. The vast majority of these combinations of drugs (especially where 3 or more drugs are involved) have never been studied at all, let alone in double-blind trials ( with the exception of Oncology/AIDS treatment, where the toxicity of the drugs demands study); yet it is frequent practice to prescribe these multiple-drug combinations.
It is well accepted in Pharmacology that it is scientifically impossible to accurately predict the side effects or clinical effects of a combination of drugs without studying that particular combination of drugs in test subjects. Knowledge of the pharmacologic profiles of the individual drugs in question does not in any way assure accurate prediction of the side effects of combinations of those drugs, especially when they have different mechanisms of action, which is very common because polypharmacy is most often prescribed to patients with “multiple illnesses”. More than 100,000 patients in this country die from identified adverse drug reactions (perhaps the 4th to 6th leading cause of death in the U.S.)3 The number who die as a consequence of polypharmacy is, to my knowledge, unknown.
The argument that the prescribing of drugs is the “Art” of Medicine is not valid in defending polypharmacy, because drugs are developed (indications, dose and administration, etc.) and approved through a “scientific” process (double-blind, placebo-controlled studies). The fact that the medicines are often prescribed for “different conditions” is irrelevant (especially to the patient’s physiology). The idea that ” we are doing the best we can “, a frequent defense of Polypharmacy, does not in any way uphold a scientific argument in favor of it. (We are, indeed, trying the best we can, with tools which do not improve at the rate we would wish!) The fact that “there is a limit to how much research can be done” in no way makes the research unnecessary in order to predict the side effects of specific combinations of drugs.
It has been said in the past that From the Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis. Dr Flockhart is now with the Department of Medicine, Indiana University School of Medicine, Wishard Hospital, Indianapolis.
Abstract 2 of 8
Potential Role of Pharmacogenomics in Reducing Adverse Drug Reactions
A Systematic Review
Kathryn A. Phillips, PhD, David L. Veenstra, PhD, PharmD, Eyal Oren, BA, Jane K. Lee, BA and Wolfgang Sadee, PhD
JAMA. 2001;286:2270-2279.
Context Adverse drug reactions are a significant cause of morbidity and mortality. Although many adverse drug reactions are considered nonpreventable, recent developments suggest these reactions may be avoided through individualization of drug therapies based on genetic information, an application known as pharmacogenomics.
Objective To evaluate the potential role of pharmacogenomics in reducing the incidence of adverse drug reactions.
Data Sources MEDLINE English-language only searches for adverse drug reaction studies published between January 1995 and June 2000 and review articles of variant alleles of drug-metabolizing enzymes published between January 1997 and August 2000. We also used online resources, texts, and expert opinion.
Study Selection Detailed inclusion criteria were used to select studies. We included 18 of 333 adverse drug reaction studies and 22 of 61 variant allele review articles.
Data Extraction All the investigators reviewed and coded articles using standardized abstracting forms.
Data Synthesis We identified 27 drugs frequently cited in adverse drug reaction studies. Among these drugs, 59% are metabolized by at least 1 enzyme with a variant allele known to cause poor metabolism. Conversely, only 7% to 22% of randomly selected drugs are known to be metabolized by enzymes with this genetic variability (range, P = 006-PFrom the Foundation for Health Services Research (Drs Ebbesen and Sandvik) and the Departments of Internal Medicine (Dr Erikssen) and Pathology (Dr Svaar), Central Hospital of Akershus, Nordbyhagen, Norway; and the Norwegian Medicines Control Authority (Ms Buajordet), the Division of Clinical Pharmacology and Toxicology, Clinical Chemistry Department, Ullevaal University Hospital (Dr Brørs), and the National Institute of Forensic Toxicology (Dr Hilberg), Oslo, Norway.
Abstract 4 of 8
Analysis of Medication-Related Malpractice Claims
Causes, Preventability, and Costs
Jeffrey M. Rothschild, MD,MPH, Frank A. Federico, RPh, Tejal K. Gandhi, MD,MPH, Rainu Kaushal, MD,MPH, Deborah H. Williams, MHA and David W. Bates, MD,MSc
Arch Intern Med. 2002;162:2414-2420.
Background Adverse drug events (ADEs) may lead to serious injury and may result in malpractice claims. While ADEs resulting in claims are not representative of all ADEs, such data provide a useful resource for studying ADEs. Therefore, we conducted a review of medication-related malpractice claims to study their frequency, nature, and costs and to assess the human factor failures associated with preventable ADEs. We also assessed the potential benefits of proved effective ADE prevention strategies on ADE claims prevention.
Methods We conducted a retrospective analysis of a New England malpractice insurance company claims records from January 1, 1990, to December 31, 1999. Cases were electronically screened for possible ADEs and followed up by independent review of abstracts by 2 physician reviewers (T.K.G. and R.K.). Additional in-depth claims file reviews identified potential human factor failures associated with ADEs.
Results Adverse drug events represented 6.3% (129/2040) of claims. Adverse drug events were judged preventable in 73% (n = 94) of the cases and were nearly evenly divided between outpatient and inpatient settings. The most frequently involved medication classes were antibiotics, antidepressants or antipsychotics, cardiovascular drugs, and anticoagulants. Among these ADEs, 46% were life threatening or fatal. System deficiencies and performance errors were the most frequent cause of preventable ADEs. The mean costs of defending malpractice claims due to ADEs were comparable for nonpreventable inpatient and outpatient ADEs and preventable outpatient ADEs (mean, $64 700-74 200), but costs were considerably greater for preventable inpatient ADEs (mean, $376 500).
Conclusions Adverse drug events associated with malpractice claims were often severe, costly, and preventable, and about half occurred in outpatients. Many interventions could potentially have prevented ADEs, with error proofing and process standardization covering the greatest proportion of events.
>From the Division of General Medicine, the Department of Medicine, Brigham and Women’s Hospital (Drs Rothschild, Gandhi, Kaushal, and Bates and Ms Williams), and the Risk Management Foundation of the Harvard Medical Institutions (Mr Federico), Boston, Mass.
Abstract 5 of 8
Incidence and Impact of Adverse Drug Events in Pediatric Inpatients
Mark T. Holdsworth, PharmD, Richard E. Fichtl, PharmD, Maryam Behta, PharmD, Dennis W. Raisch, PhD, Elena Mendez-Rico, PharmD, Alexa Adams, MD, Melanie Greifer, MD, Susan Bostwick, MD and Bruce M. Greenwald, MD
Arch Pediatr Adolesc Med. 2003;157:60-65.
Objectives To determine the incidence and causes of adverse drug events (ADEs) and potential ADEs in hospitalized children, and to examine the consequences of these events.
Design Prospective review of medical records and staff interviews were performed. The ADEs were defined as injuries from medications or lack of an intended medication, and potential ADEs, as errors with the potential to result in injury.
Setting A general pediatric unit and a pediatric intensive care unit in a metropolitan medical center.
Patients A total of 1197 consecutive patient admissions were studied from September 15, 2000, to May 10, 2001. The admissions represented a total of 922 patients and 10 164 patient-days.
Results The ADEs (6/100 admissions, 7.5/1000 patient-days) and potential ADEs (8/100 admissions, 9.3/1000 patient-days) were common in hospitalized children. Demographic variables associated with the occurrence of these events were the length of hospital stay, case-mix index, and amount of medication exposure. After adjusting for length of stay, medication exposure continued to have a significant influence on ADEs and potential ADEs. For ADEs, 18 (24%) were judged to be serious or life threatening. Most ADEs were not associated with major or permanent disability. Patients with both ADEs and potential ADEs were less likely to be routinely discharged and more likely to be discharged with home health care or to another institution, suggesting that patient disposition was not related to the adverse event.
Conclusions Both ADEs and potential ADEs are common among hospitalized children with greater disease burden and medication exposure. These findings suggest that these events were a consequence, rather than a cause, of more severe illness.
>From the College of Pharmacy, University of New Mexico, Albuquerque (Dr Holdsworth); Departments of Pharmacy (Drs Fichtl, Behta, and Mendez-Rico) and Pediatrics (Drs Adams and Greifer), New York-Presbyterian Hospital, New York, NY; Veterans Affairs Cooperative Studies Program Research Pharmacy Coordinating Center, Albuquerque (Dr Raisch); and Department of Pediatrics, Joan and Sanford I. Weill Medical College of Cornell University, New York (Drs Bostwick and Greenwald).
Abstract 6 of 8
Drug-Drug Interactions Among Elderly Patients Hospitalized for Drug Toxicity
David N. Juurlink, MD, FRCPC, Muhammad Mamdani, PharmD, MPH, Alexander Kopp, Andreas Laupacis, MD, MSc and Donald A. Redelmeier, MD, MSc
JAMA. 2003;289:1652-1658.
Context Drug-drug interactions are a preventable cause of morbidity and mortality, yet their consequences in the community are not well characterized.
Objective To determine whether elderly patients admitted to hospital with specific drug toxicities were likely to have been prescribed an interacting drug in the week prior to admission.
Design Three population-based, nested case-control studies.
Setting Ontario, Canada, from January 1, 1994, to December 31, 2000.
Patients All Ontario residents aged 66 years or older treated with glyburide, digoxin, or an angiotensin-converting enzyme (ACE) inhibitor. Case patients were those admitted to hospital for drug-related toxicity. Prescription records of cases were compared with those of controls (matched on age, sex, use of the same medication, and presence or absence of renal disease) for receipt of interacting medications (co-trimoxazole with glyburide, clarithromycin with digoxin, and potassium-sparing diuretics with ACE inhibitors).
Main Outcome Measure Odds ratio for association between hospital admission for drug toxicity (hypoglycemia, digoxin toxicity, or hyperkalemia, respectively) and use of an interacting medication in the preceding week, adjusted for diagnoses, receipt of other medications, the number of prescription drugs, and the number of hospital admissions in the year preceding the index date.
Results During the 7-year study period, 909 elderly patients receiving glyburide were admitted with a diagnosis of hypoglycemia. In the primary analysis, those patients admitted for hypoglycemia were more than 6 times as likely to have been treated with co-trimoxazole in the previous week (adjusted odds ratio, 6.6; 95% confidence interval, 4.5-9.7). Patients admitted with digoxin toxicity (n = 1051) were about 12 times more likely to have been treated with clarithromycin (adjusted odds ratio, 11.7; 95% confidence interval, 7.5-18.2) in the previous week, and patients treated with ACE inhibitors admitted with a diagnosis of hyperkalemia (n = 523) were about 20 times more likely to have been treated with a potassium-sparing diuretic (adjusted odds ratio, 20.3; 95% confidence interval, 13.4-30.7) in the previous week. No increased risk of drug toxicity was found for drugs with similar indications but no known interactions (amoxicillin, cefuroxime, and indapamide, respectively).
Conclusions Many hospital admissions of elderly patients for drug toxicity occur after administration of a drug known to cause drug-drug interactions. Many of these interactions could have been avoided.
Author Affiliations: Sunnybrook and Women’s College Health Sciences Centre; the Clinical Epidemiology and Healthcare Research Program, and Departments of Medicine (Drs Juurlink, Laupacis, and Redelmeier), and Pharmacy (Dr Mamdani), University of Toronto; and the Institute for Clinical Evaluative Sciences (Drs Juurlink, Mamdani, Laupacis, and Redelmeier, and Mr Kopp), Toronto, Ontario.
Abstract 7 of 8
Incidence of Adverse Drug Reactions in Hospitalized Patients
A Meta-analysis of Prospective Studies
Jason Lazarou, MSc, Bruce H. Pomeranz, MD, PhD and Paul N. Corey, PhD
JAMA. 1998;279:1200-1205.
Objective. To estimate the incidence of serious and fatal adverse drug reactions (ADR) in hospital patients.
Data Sources. Four electronic databases were searched from 1966 to 1996.
Study Selection. Of 153, we selected 39 prospective studies from US hospitals.
Data Extraction. Data extracted independently by 2 investigators were analyzed by a random-effects model. To obtain the overall incidence of ADRs in hospitalized patients, we combined the incidence of ADRs occurring while in the hospital plus the incidence of ADRs causing admission to hospital. We excluded errors in drug administration, noncompliance, overdose, drug abuse, therapeutic failures, and possible ADRs. Serious ADRs were defined as those that required hospitalization, were permanently disabling, or resulted in death.
Data Synthesis. The overall incidence of serious ADRs was 6.7% (95% confidence interval [CI], 5.2%-8.2%) and of fatal ADRs was 0.32% (95% CI, 0.23%-0.41%) of hospitalized patients. We estimated that in 1994 overall 2216000 (1721000-2711000) hospitalized patients had serious ADRs and 106000 (76000-137000) had fatal ADRs, making these reactions between the fourth and sixth leading cause of death.
Conclusions. The incidence of serious and fatal ADRs in US hospitals was found to be extremely high. While our results must be viewed with circumspection because of heterogeneity among studies and small biases in the samples, these data nevertheless suggest that ADRs represent an important clinical issue.
>From the Departments of Zoology (Mr Lazarou and Dr Pomeranz), Physiology (Dr Pomeranz), and Public Health Sciences (Dr Corey), University of Toronto, Toronto, Ontario.
Abstract 8 of 8
Timing of New Black Box Warnings and Withdrawals for Prescription Medications
Karen E. Lasser, MD,MPH, Paul D. Allen, MD,MPH, Steffie J. Woolhandler, MD,MPH, David U. Himmelstein, MD, Sidney M. Wolfe, MD and David H. Bor, MD
JAMA. 2002;287:2215-2220.
Context Recently approved drugs may be more likely to have unrecognized adverse drug reactions (ADRs) than established drugs, but no recent studies have examined how frequently postmarketing surveillance identifies important ADRs.
Objective To determine the frequency and timing of discovery of new ADRs described in black box warnings or necessitating withdrawal of the drug from the market.
Design and Setting Examination of the Physicians’ Desk Reference for all new chemical entities approved by the US Food and Drug Administration between 1975 and 1999, and all drugs withdrawn from the market between 1975 and 2000 (with or without a prior black box warning).
Main Outcome Measures Frequency of and time to a new black box warning or drug withdrawal.
Results A total of 548 new chemical entities were approved in 1975-1999; 56 (10.2%) acquired a new black box warning or were withdrawn. Forty-five drugs (8.2%) acquired 1 or more black box warnings and 16 (2.9%) were withdrawn from the market. In Kaplan-Meier analyses, the estimated probability of acquiring a new black box warning or being withdrawn from the market over 25 years was 20%. Eighty-one major changes to drug labeling in the Physicians’ Desk Reference occurred including the addition of 1 or more black box warnings per drug, or drug withdrawal. In Kaplan-Meier analyses, half of these changes occurred within 7 years of drug introduction; half of the withdrawals occurred within 2 years.
Conclusions Serious ADRs commonly emerge after Food and Drug Administration approval. The safety of new agents cannot be known with certainty until a drug has been on the market for many years.
Author Affiliations: Department of Medicine, Cambridge Hospital and Harvard Medical School, Cambridge, Mass (Drs Lasser, Allen, Woolhandler, Himmelstein, and Bor); and Public Citizen Health Research Group, Washington, DC (Dr Wolfe).
sorry last one got cut off:
Presented by the author at the 2003 New England Forensic Sciences Conference at Colby College:
Polypharmacy: What Cost in Morbidity and Mortality?©
It is common practice in Medicine/Psychiatry to put patients on combinations of drugs. The vast majority of these combinations of drugs (especially where 3 or more drugs are involved) have never been studied at all, let alone in double-blind trials ( with the exception of Oncology/AIDS treatment, where the toxicity of the drugs demands study); yet it is frequent practice to prescribe these multiple-drug combinations.
It is well accepted in Pharmacology that it is scientifically impossible to accurately predict the side effects or clinical effects of a combination of drugs without studying that particular combination of drugs in test subjects. Knowledge of the pharmacologic profiles of the individual drugs in question does not in any way assure accurate prediction of the side effects of combinations of those drugs, especially when they have different mechanisms of action, which is very common because polypharmacy is most often prescribed to patients with “multiple illnesses”. More than 100,000 patients in this country die from identified adverse drug reactions (perhaps the 4th to 6th leading cause of death in the U.S.)3 The number who die as a consequence of polypharmacy is, to my knowledge, unknown.
The argument that the prescribing of drugs is the “Art” of Medicine is not valid in defending polypharmacy, because drugs are developed (indications, dose and administration, etc.) and approved through a “scientific” process (double-blind, placebo-controlled studies). The fact that the medicines are often prescribed for “different conditions” is irrelevant (especially to the patient’s physiology). The idea that ” we are doing the best we can “, a frequent defense of Polypharmacy, does not in any way uphold a scientific argument in favor of it. (We are, indeed, trying the best we can, with tools which do not improve at the rate we would wish!) The fact that “there is a limit to how much research can be done” in no way makes the research unnecessary in order to predict the side effects of specific combinations of drugs.
It has been said in the past that
nutz!
last paragraph:
It has been said in the past that