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Results for “Polypharmacy”

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PubMed2004

The Warfarin/Aspirin Study in Heart failure (WASH): a randomized trial comparing antithrombotic strategies for patients with heart failure.

BACKGROUND: Heart failure is commonly associated with vascular disease and a high rate of athero-thrombotic events, but the risks and benefits of antithrombotic therapy are unknown. METHODS: The current study was an open-label, randomized, controlled trial comparing no antithrombotic therapy, aspirin (300 mg/day), and warfarin (target international normalized ratio 2.5) in patients with heart failure and left ventricular systolic dysfunction requiring diuretic therapy. The primary objective was to demonstrate the feasibility and inform the design of a larger outcome study. The primary clinical outcome was death, nonfatal myocardial infarction, or nonfatal stroke. RESULTS: Two hundred seventy-nine patients were randomized and 627 patient-years exposure were accumulated over a mean follow-up time of 27 +/- 1 months. Twenty-six (26%), 29 (32%), and 23 (26%) patients randomized to no antithrombotic treatment, aspirin, and warfarin, respectively, reached the primary outcome (ns). There were trends to a worse outcome among those randomized to aspirin for a number of secondary outcomes. Significantly (P =.044) more patients randomized to aspirin were hospitalized for cardiovascular reasons, especially worsening heart failure. CONCLUSIONS: The Warfarin/Aspirin Study in Heart failure (WASH) provides no evidence that aspirin is effective or safe in patients with heart failure. The benefits of warfarin for patients with heart failure in sinus rhythm have not been established. Antithrombotic therapy in patients with heart failure is not evidence based but commonly contributes to polypharmacy.

Aged↗

PubMed2005

Olanzapine-induced vasculitis.

INTRODUCTION: Elderly patients are particularly vulnerable to adverse drug reactions as a result of polypharmacy and metabolic changes associated with aging. We present a case of leukocytoclastic vasculitis induced by olanzapine, a medication commonly used in elderly patients. CASE SUMMARY: An 82-year-old woman was admitted to the extended-care center for short-term rehabilitation after prolonged hospitalization for a pulmonary embolism requiring mechanical ventilation. The pulmonary problem resolved, but her hospitalization and subsequent rehabilitation were complicated by agitated delirium, which was treated with olanzapine and modification of contributory factors. At the time of admission to the rehabilitation facility, the patient had been receiving warfarin for 2 weeks and olanzapine for 6 days. On the eighth day after initiation of olanzapine, erythematous skin lesions developed on dependent areas. The international normalized ratio for warfarin was within the acceptable range; however, because warfarin has been associated with subcutaneous bleeding presenting as petechiae and ecchymosis, subcutaneous enoxaparin was substituted for warfarin. The skin lesions continued to worsen over the next week and developed into palpable lesions. Biopsy of the rash revealed leukocytoclastic vasculitis. In the absence of another cause, olanzapine was discontinued and the rash improved significantly. When the agitation recurred, risperidone was initiated, but the patient experienced dizziness with this agent. Olanzapine was resumed and the skin lesions recurred. Olanzapine was then changed to quetiapine, and the skin lesions improved over the next few weeks. DISCUSSION: Olanzapine is commonly used in elderly patients to control behavioral disturbances associated with dementia, delirium, and other psychiatric disorders. Leukocytoclastic vasculitis is an infrequently reported adverse drug reaction with olanzapine. Its exact pathogenic mechanism is unknown, but both cell-mediated and humoral immunity appear to play important roles. Because drug-induced vasculitis has an identical clinical presentation and identical serologic/pathologic parameters to idiopathic forms of vasculitis, a high index of suspicion is necessary for its accurate diagnosis. CONCLUSIONS: Because adverse drug reactions are common in elderly patients taking multiple medications, physicians should be vigilant when starting new medications and should attempt to eliminate unnecessary medications. Clinicians should be aware of the potential for leukocytoclastic vasculitis in association with olanzapine.

Aged↗

PubMed2006

The cell cycle hypothesis of Alzheimer's disease: suggestions for drug development.

The cell cycle of hypothesis of neural dysfunction in chronic neurodegenerative conditions such as Alzheimer's disease (AD) offers a unified approach to understanding both existing and novel strategies for drug development. At the present time, a ligand based approach is a pragmatic solution for identifying new chemical leads on which to base future discovery and optimisation. We have pursued a ligand based approach on the basis of public domain data to identify existing compounds capable of abrogating the cell cycle at the G0-G1 interface. Selected on this basis, irrespective of the tissue under study, we identified several classes of compounds as potential chemical leads. Of these compounds, at least ten have already been shown to be neuroprotective in animal models of acute neurodegeneration. Such compounds could form the basis of a screening exercise after development of suitable screening tools. Progressing of chemical leads through such an approach will be more efficient if future leads display relevant "drug-like" properties. Further, drug development in this arena should take account of the special concerns raised by targeting an elderly population. This will involve accounting for frequent polypharmacy in the aging population, and age-related alterations in physiology.

Aged↗

PubMed2006

Selected Proceedings of the NICHD/FDA newborn drug development initiative: Part II.

BACKGROUND: In February 2003, the National Institute of Child Health and Human Development (NICHD) and the US Food and Drug Administration (FDA) created the Newborn Drug Development Initiative (NDDI), an ongoing program to determine gaps in knowledge in neonatal therapeutics and to explore clinical study designs for use in the newborn population. Working groups were established in 3 therapeutic areas: the central nervous, pulmonary, and cardiovascular systems. Three additional groups discussed pain control, drug prioritization, and ethics in neonatal clinical trials. OBJECTIVE: The purpose of this article was to provide an overview of the 5 articles written by members of the Neurology, Cardiology, Drug Prioritization, and Ethics Groups. METHODS: Information for the current article, as well as the 5 articles presented in this supplemental section, was gathered from the proceedings of a workshop cosponsored by the NICHD and the FDA. This workshop took place March 29 and 30, 2004, in Baltimore, Maryland. RESULTS: The Neurology Group addressed the treatment of 2 common and interrelated conditions in the newborn population: neonatal seizures and hypoxic-ischemic encephalopathy. The unsubstantiated clinical preference for using phenobarbital to treat neonatal seizures, coupled with the development of several newer antiepileptic drugs with application in children, dictates the need for rigorous clinical trials of these drugs in the neonatal population. A number of pharmacologic agents currently undergoing extensive investigations in experimental animals and adult humans may have application in the newborn population. The Cardiology Group reviewed controversial approaches to the diagnosis and treatment of cardiovascular instability of preterm infants and identified gaps in knowledge. The group discussed issues of study design and developed 2 study proposals: (1) a placebo-controlled trial with a rescue arm for symptomatic infants; and (2) a targeted blood pressure (BP) trial. The Drug Prioritization Group focused on the fact that the uniqueness of the newborn population is due to distinctive and changing physiologic characteristics, conditions, and diseases that are different from those affecting older children, as well as the large differences in developmental patterns between 23 weeks of gestation and term. All of these factors help explain the lack of adequate trials and the sparseness of evidence regarding efficacy and toxicity risks of most drugs used in the newborn population. Unfortunately, the frequency of drug use and polypharmacy is highest in very-low-birth-weight infants. The large number of drugs requiring study and the uniqueness of the indications for those drugs preclude the use of the prioritization process used in older children. The focus of the Drug Prioritization Group was the determination of factors that identify which drugs are most important for study. The Ethics Group was unique in that its members were integrated into the therapeutic groups. This approach allowed for the identification of similarities and dissimilarities in the proposed clinical trial design framework. The summary report included here identifies common themes voiced in the various NDDI reports and deliberations. CONCLUSIONS: The 5 articles included in this issue address different issues but share common themes: the need to develop innovative trial designs and biomarkers of efficacy, consideration of ethical concerns, and selection of appropriate drugs for study.

Drug Approval↗

PubMed2006

The German hospital malnutrition study.

BACKGROUND & AIMS: Malnutrition is frequently observed in chronic and severe diseases and associated with impaired outcome. In Germany general data on prevalence and impact of hospital malnutrition are missing. METHODS: Nutritional state was assessed by subjective global assessment (SGA) and by anthropometric measurements in 1,886 consecutively admitted patients in 13 hospitals (n=1,073, university hospitals; n=813, community or teaching hospitals). Risk factors for malnutrition and the impact of nutritional status on length of hospital stay were analyzed. RESULTS: Malnutrition was diagnosed in 27.4% of patients according to SGA. A low arm muscle area and arm fat area were observed in 11.3% and 17.1%, respectively. Forty-three % of patients 70 years old were malnourished compared to only 7.8% of patients <30 years. The highest prevalence of malnutrition was observed in geriatric (56.2%), oncology (37.6%), and gastroenterology (32.6%) departments. Multivariate analysis revealed three independent risk factors: higher age, polypharmacy, and malignant disease (all P<0.01). Malnutrition was associated with an 43% increase of hospital stay (P<0.001). CONCLUSIONS: In German hospitals every fourth patient is malnourished. Malnutrition is associated with increased length of hospital stay. Higher age, malignant disease and major comorbidity were found to be the main contributors to malnutrition. Adequate nutritional support should be initiated in order to optimize the clinical outcome of these patients.

Adolescent↗

PubMed2026

Pharmacogenomic and drug interactions risk in cardio-oncology: A precision medicine perspective for India.

Cardio-oncology patients may face complex treatment regimens due to the concurrent existence of cancer and cardiovascular disease, leading to a considerable polypharmacy burden. This significantly increases the prospect of drug-drug interactions (DDIs) and gene-drug interactions. The majority of these interactions arise from comparable pharmacokinetic and pharmacological pathways associated with drug transporters and cytochrome P450 enzymes. The significance of pharmacogenomics in tailored treatment strategies are emphasised by the fact that genetic variability enhances individual differences in drug response, safety, and efficacy. This narrative review focus on the effects of key genetic polymorphisms (e.g., DPYD, CYP2C19, and CYP2C9) on the metabolism and efficacy of commonly prescribed anticancer and cardiovascular medications such as fluoropyrimidines, clopidogrel, and warfarin. In addition it explore the role of pharmacogenomic variants on drug-drug interactions within the field of cardio-oncology. The study ultimately emphasizes the necessity of precision medicine in India to address the genetic diversity and underrepresentation in global genomic databases. The absence of pharmacogenomic testing, infrastructural deficiencies, financial constraints, and insufficient clinical integration hinder the widespread use of this technology in India. The Genome India Project and other national initiatives establish the foundation for pharmacogenomic-guided therapy. Utilizing genetic data, together with artificial intelligence-based predictive tools, for clinical decision-making may enhance medication safety and yield optimal outcomes in Indian cardio-oncology patients.

Humans↗

PubMed2003

Understanding and preventing drug interactions in elderly patients.

The elderly consume a disproportionate amount of prescription and nonprescription medications. Alterations in physiology, polypharmacy, multiple prescribers, and other factors place the elderly population at risk of developing clinically significant drug-drug interactions. The incidence of potential drug-drug interactions increases with increased drug use and are responsible for numerous emergency room and physician visits. Drug interactions have been shown to cause a decline in functional abilities in older people. Drugs can interact to alter the absorption, distribution, metabolism, or excretion of a drug or interact in a synergistic or antagonist fashion altering their pharmacodynamics. Drug interactions are often clinically unrecognized and responsible for increased morbidity in elderly patients. Prudent use of medications and vigilant drug monitoring are essential to avoid drug-drug interactions.

Aged↗

PubMed2005

Incidence of cancer after immunosuppressive treatment for heart transplantation.

Prolonged or intensive immunosuppressive therapy used after organ transplantation is complicated by an increased incidence of cancer. Striking differences in incidence are observed in heart and heart-lung transplant recipients when compared with renal transplant patients. The most significant increase was in the incidence of lymphomas in cardiac versus renal patients. Moreover, a two-fold greater increase of all neoplasms was found in cardiac recipients, with nearly a six-fold increase in visceral tumors. Several factors may account for these differences. In cardiac allograft recipients, intensive immunosuppression is frequently used to reverse acute rejection and the highest number of cardiac transplants was performed in the era of polypharmacy, usually consisting of triple therapy.

Heart Transplantation↗

PubMed2004

Treatment implications for radiation-induced nausea and vomiting in specific patient groups.

Radiation-induced nausea and vomiting (RINV) affect the management and quality of life of cancer patients. Current guidelines for RINV prevention recommend prophylaxis with a 5-hydroxytryptamine (5-HT(3))-receptor antagonist for patients receiving moderately or highly emetogenic radiotherapy regimens. Randomised trials have compared such antagonists with conventional antiemetics, and have demonstrated their efficacy and safety. Special consideration is needed for antiemetic treatment in certain patient groups, particularly the elderly and those with renal or hepatic impairment. Radiation oncologists should be aware of the effect on antiemetic treatment of factors such as comorbid conditions (particularly cardiovascular disease), polypharmacy and drug-drug interactions, and choose the agent with the lowest potential for additional complications. The most appropriate antiemetic treatment to improve patient compliance and quality of life should ideally combine proven efficacy with uncomplicated administration and convenient dosing regimens.

Age Factors↗

PubMed2007

International Society of Geriatric Oncology (SIOG) recommendations for the adjustment of dosing in elderly cancer patients with renal insufficiency.

A SIOG taskforce was formed to discuss best clinical practice for elderly cancer patients with renal insufficiency. This manuscript outlines recommended dosing adjustments for cancer drugs in this population according to renal function. Dosing adjustments have been made for drugs in current use which have recommendations in renal insufficiency and the elderly, focusing on drugs which are renally eliminated or are known to be nephrotoxic. Recommendations are based on pharmacokinetic and/or pharmacodynamic data where available. The taskforce recommend that before initiating therapy, some form of geriatric assessment should be conducted that includes evaluation of comorbidities and polypharmacy, hydration status and renal function (using available formulae). Within each drug class, it is sensible to use agents which are less likely to be influenced by renal clearance. Pharmacokinetic and pharmacodynamic data of anticancer agents in the elderly are needed in order to maximise efficacy whilst avoiding unacceptable toxicity.

Aged↗

PubMed2005

A statin in the treatment of heart failure? Controlled rosuvastatin multinational study in heart failure (CORONA): study design and baseline characteristics.

BACKGROUND: Previous prospective outcome studies of statins have not provided any guidance on benefit-risk in patients with heart failure. AIM: The primary objective is to determine whether rosuvastatin (10 mg) reduces the combined endpoint of cardiovascular mortality, non-fatal myocardial infarction or non-fatal stroke (time to first event). The first secondary endpoint is all-cause mortality. METHODS: CORONA is a randomized, double-blind, placebo-controlled trial. Briefly, men and women, aged > or =60 years with chronic symptomatic systolic heart failure of ischemic aetiology and ejection fraction < or =0.40 (NYHA class III and IV) or < or =0.35 (NYHA class II) were eligible if they were not using or in need of cholesterol lowering drugs. RESULTS: Mean age was 73 years (n=5016; 24% women), with 37% in NYHA II and 62% in NYHA III, ejection fraction 0.31, total cholesterol 5.2 mmol/L. Sixty percent have a history of myocardial infarction, 63% hypertension, and 30% diabetes. Patients are well treated for heart failure with 90% on loop or thiazide diuretics, 42% aldosterone antagonists, 91% ACE inhibitor or AT-I blocker, 75% beta-blockers, and 32% digitalis. CONCLUSION: CORONA is important for three main reasons: (1) A positive result is very important because of the high risk of the population studied, the increasing prevalence of elderly patients with chronic symptomatic systolic heart failure in our society, and the health economic issues involved. (2) If negative, new mechanistic questions about heart failure have to be raised. (3) If neutral we can avoid unnecessary polypharmacy.

Age Factors↗

PubMed2005

Can opioids prevent post-operative chronic pain?

Chronic post-operative pain is a major source of suffering and disability. Better standardisation for assessing and reporting chronic post-operative pain is needed. Peripheral and central nervous plasticity seem to play a major role in the development of chronic post-injury pain. Complex mechanisms, including several receptor systems and messenger systems are involved. Thus, it is unlikely that one single agent will solve the problem. Opioids have proven effect both in animal models, experimental human models, and in some clinical models. Timing and dose seem to be of importance. However, it is likely that polypharmacy and multi-modal treatment is necessary to further improve the preventive strategy.

Acute Disease↗

PubMed2005

Opioid use in the elderly.

Pain treatment in the elderly is an important challenge to Western societies due to increasing numbers of old persons, their higher incidence of pain, and their greater susceptibility to adverse effects of pain medication. We provide an overview of the factors liable to influence opioid action in the elderly population. A major challenge for the physician prescribing opioids in the elderly is their greater risk of medication-associated problems. Thus, older patients suffer increased vulnerability to adverse drug effects and interactions, higher rates of polypharmacy, and more comorbidity. These problems are compounded by a relative lack of definitive published information. There is clearly a need for more research in this area. Aging affects opioid pharmacokinetics via altered body composition (distribution volumes) and organ function (liver=metabolism, kidney=excretion). Pharmacodynamics is affected via impaired neurotransmitter/peptide production and changed receptor affinities/populations. Older women may need less morphine analgesia postoperatively, while pain sensitivity tends to increase particularly in older men. However, the net effects of changes in opioid pharmacology with age on clinical opioid analgesia remain unclear, probably due to the significantly greater variability in body function with increasing age. Practical recommendations for opioid prescription in the elderly include meticulous review of indication for opioid use, not only initially but also at regular intervals thereafter. A policy of careful titration should be followed, with conservative choice of dosage on starting. Dosing intervals may need to be lengthened subsequently. Finally, it should be remembered that old persons do not necessarily need less opioid than younger ones.

Aged↗

PubMed2004

Clinical effectiveness of atypical antipsychotics in elderly patients with psychosis.

The elderly represent a unique patient group in the sense that they have a high prevalence of psychotic symptoms that are a manifestation of a variety of psychiatric, neurological and organic disorders. Treatment is complicated by several factors including comorbid diagnoses (psychiatric and medical), polypharmacy, age-related changes in pharmacokinetics and pharmacodynamics and high susceptibility to adverse events. Elderly patients require pharmacological interventions that are effective in reducing symptoms but also are well tolerated, improve everyday functioning, subjective well-being and treatment adherence and reduce family/career burden. The ability of an antipsychotic to fulfil these requirements determines its clinical effectiveness. To date, few studies have investigated the clinical effectiveness of atypical antipsychotics in elderly patients. However, clear differences exist between the available agents, particularly with regard to tolerability profiles, which have a major impact on the clinical outcome of patients. Clinicians should select an agent that is not only effective in reducing psychotic symptoms but, more importantly, one that has a low incidence of adverse events, such as extrapyramidal symptoms (EPS) and neurocognitive problems, which are of concern in the elderly.

Aged↗

PubMed2006

Generalized anxiety disorder: A comorbid disease.

Generalized anxiety disorder (GAD) frequently occurs comorbidly with other conditions, including depression and somatic complaints. Comorbid GAD sufferers have increased psychologic and social impairment, request additional treatment, and have an extended course and poorer outcome than those with GAD alone; therapy should alleviate both the psychic and somatic symptoms of GAD without negatively affecting the comorbid condition. The ideal treatment would provide relief from both GAD and the comorbid condition, reducing the need for polypharmacy. Physicians need suitable tools to assist them in the detection and monitoring of GAD patients-the GADI, a new, self-rating scale, may meet this requirement. Clinical data have shown that various neurobiologic irregularities (e.g., in the GABA and serotonin systems) are associated with the development of anxiety. Prescribing physicians must take into account these abnormalities when choosing a drug. Effective diagnosis and treatment should improve patients' quality of life and their prognosis for recovery.

Agoraphobia↗

PubMed2005

Effective maintenance treatment--breaking the cycle of bipolar disorder.

Clinical guidelines for treatment and research of bipolar disorder greatly benefit from the synthesis of data from individual studies. The British Association for Psychopharmacology bases its guidelines on evidence from opinions (level D) to systematic reviews of primary trial data (level A). The report details conclusions of its 1-day consensus meeting to develop guidelines covering diagnosis, clinical management, pharmacotherapy for acute episodes, relapse prevention and treatment discontinuation. Monotherapy for long-term management is preferred, having reduced side-effects and drug interactions and improved compliance. Combination therapy is often preferred for acute episodes, using antipsychotics for mania or antidepressants for depression. Increased efficacy may be attributed to multiple mechanisms of action and potentially lower doses. In clinical practice, maintenance monotherapy has limited success for chronic episodes and polypharmacy is frequently used, though the best combination remains unclear. A new collaborative approach based on simple clinical trials is required to change current medical practice.

Antimanic Agents↗

PubMed2005

Drug-induced proarrhythmia and use of QTc-prolonging agents: clues for clinicians.

Use of drugs with the potential for prolongation of the QTc interval and proarrhythmia is a growing challenge facing clinicians. Many pharmaceutical agents have been denied approval for human use, approved with restrictions and warnings regarding proarrhythmia, or withdrawn from the market based upon arrhythmic risk. Despite known risk factors for QTc prolongation and drug-induced arrhythmia, precise prediction of the risk of torsades de pointes (TdP) in an individual patient remains difficult. The mechanism of drug-induced TdP typically involves use of an agent that blocks the I(Kr) cardiac potassium current, often in combination with risk-amplifying factors such as high drug levels, reduced drug metabolism, polypharmacy, and patient-specific factors such as gender, age, and genetic polymorphism. For the clinician, an integrated approach involving appreciation of the risk factors for proarrhythmia combined with computer-based risk assessment is the best method for reducing the risk of drug-induced proarrhythmia in clinical practice.

Anti-Arrhythmia Agents↗

PubMed2006

Clonidine-induced delirium.

Clonidine-induced delirium has rarely been reported. To the best of our knowledge, there are six related case reports in the literature. We describe one such case here and review the six previously published cases. Clonidine may induce a variety of psychological side effects ranging from depression to acute hallucination and delirium. However, there are no clearly identifiable risk factors for the development of severe psychological side effects, including dose of medication, duration of treatment, and predisposing mental illness. Treatment for clonidine-induced delirium involves cessation of the medication and patient observation. Given the large clinical burden of hypertension and the not uncommon requirement for polypharmacy to achieve blood pressure goals, heightened clinical awareness of this potential side effect appears justified.

Adrenergic alpha-Agonists↗