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PubMed2003

Determination of serum reboxetine enantiomers in patients on chronic medication with racemic reboxetine.

The chiral compound reboxetine is used as a selective noradrenaline reuptake inhibitor (NARI) for the treatment of major depressive disorders. The pharmacokinetic variability of the enantiomers of the drug (S,S- and R,R-reboxetine) was studied using stereoselective high-performance liquid chromatography with mass spectrometric detection in a controlled clinical monotherapy situation (trial I) and a naturalistic clinical setting (trial II). Trial I included patients receiving racemic reboxetine as 6-month monotherapy for treatment of major depressive disorder. Trough level serum samples in steady state were analyzed for the concentration of the reboxetine enantiomers in study weeks 4, 12, and 24. In a therapeutic drug monitoring setting (trial II), 47 patients on doses ranging from 4 to 16 mg daily, including much polypharmacy, trough level steady-state serum samples were analyzed by the same bioanalytical method. Data from trials I and II were assessed to determine the inter- and intraindividual pharmacokinetic outcomes. The results showed that the median S,S/R,R ratio in steady state was 0.5 and ranged from 0.22 to 0.88. It was also shown that women have an approximately 30% higher S,S/R,R ratio than men. The S,S/R,R ratios of reboxetine were not found to correlate with reboxetine concentrations. To investigate the NARI activity of a circulating serum reboxetine concentration, a recalculation of the determined enantiomeric concentrations to previously demonstrated experimental NARI potencies of the drug enantiomers was performed. This partly novel concept of estimating pharmacodynamic activity showed that the serum NARI activity in women tended to be higher than in men at a given reboxetine concentration. In conclusion, the variability in the NARI activity per nmol/L reboxetine and the variability in the concentration outcome of the reboxetine enantiomers may justify the use of enantioselective drug monitoring in the clinic. The gender aspects of the drug have to be further assessed.

Adrenergic Uptake Inhibitors↗

PubMed2002

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and rhabdomyolysis: considerations in the renal failure patient.

An intense debate has developed as to the risk-benefit ratio of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) following the withdrawal of cerivastatin. The development of rhabdomyolysis in cerivastatin-treated patients should have surprised few since myotoxicity is an accepted class effect of statins. What has sprung from the cerivastatin experience though is a concern for other members of this class. Such misgivings, although understandable, are ill advised. Without question, differences exist in the risk of rhabdomyolysis occurrence amongst the various statins. In this regard, pravastatin and fluvastatin are least likely to produce rhabdomyolysis, which, in part, relates to the fact they are not metabolized by the cytochrome P450 3A4 pathway. When muscle damage occurs with statins it is most often the result of a drug-drug interaction rather than a specific adverse response to statin monotherapy. Such drug-drug interactions increase plasma concentrations of a statin and thereby increase the risk of myotoxicity. A growing consensus exists which supports an expanded use of statins in a range of patient groups including the renal failure patient. Polypharmacy and altered drug metabolism increase the risk of myotoxicity, albeit to an ill-defined degree, in this population. Many factors should enter into the choice of a statin in the multiply medicated renal failure patient.

Clinical Trials as Topic↗

PubMed1996

Avoiding Overmedication of Elderly Patients.

Overmedication is the use of drugs that are not clinically indicated and are given in an inappropriate or overly aggressive manner even when nonpharmacologic alternatives are more suitable. This is an extension of polypharmacy and is caused when age-related changes in pharmacokinetics, pharmaco-dynamics, and potential drug interactions are ignored, when inappropriate drugs are used, or when a drug is prescribed for the wrong diagnosis in elderly individuals. Overmedication can cause adverse drug reactions, increased drug costs, and noncompliance with therapeutic regimens. This phenomenon can occur in the acute care or long-term care setting, and the community-dwelling elderly can also be exposed through the use of prescription and nonprescription drugs. Strategies to prevent overmedication in the elderly are discussed.

Journal Article↗

PubMed1996

Therapeutic Drug Monitoring in the Elderly.

Therapeutic drug monitoring (TDM) is defined as the strategy by which the dosing regimen for a patient is guided by repealed measurements of plasma drug concentrations. TDM is also used to confirm drug poisoning and toxicity, to diagnose adverse drug reactions, and to verify patient compliance with drug regimens. There is a scarcity of data about the use of TDM in treating the elderly, but general inferences can be made based on pharmacokinetic and pharmacodynamic studies in older populations and on investigations in younger individuals. Despite its important limitations TDM seems to be an important tool in drug therapy management in the elderly given the increased frequency of chronic medical conditions, polypharmacy, drug interactions, and the atypical presentation of adverse drug reactions in this population.

Journal Article↗

PubMed2000

Recognition and management of depression in primary care: a focus on the elderly. A pharmacotherapeutic overview of the selection process among the traditional and new antidepressants.

Depressed patients consult with their primary care physician before engaging the services of a mental health care provider. Primary care physicians initiate more antidepressant pharmacotherapy than psychiatrists. Major depression has been estimated to have a 5% to 10% prevalence, with up to three times that percentage having significant subsyndromal depression symptoms. Patients frequently deny their depression, often neglecting to recognize their own somatic and cognitive/behavioral subjective symptoms, underestimating symptom severity, and possessing a reluctance to validate their existence because of social stigmata. There remains an underrecognition of the diagnosis of depression by primary care physicians. Often, depressed primary care patients present with somatic symptoms, which include gastrointestinal, skeletal muscle, and cardiovascular complaints, as opposed to describing nonsomatic criteria for depression. Elderly patients presenting with depression have an estimated prevalence of 5% to 50%, and the rate of suicide increases with age. In this patient group, depression may exist independently or secondary to insults or events. Major depressive disorders occur throughout the life cycle; however, the rate of major depression has increased, and the age of onset has become younger. Not uncommonly, complicating psychosocial factors coupled with multiple chronic disease states and physical pathology may mask the diagnosis of depression. Furthermore, up to 25% of extended care facility patients may satisfy the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria for depression. Comorbid diseases and pharmacotherapy have been associated with secondary depression. Antidepressant pharmacotherapy combined with cognitive and behavioral therapy appears to offer the most benefit to the patient. Antidepressants independently act as catalysts to facilitate or correct the dysregulation of neurotransmission in depressed patients. The elderly present pharmacotherapeutic challenges based on a changing internal milieu in the absorption, distribution, metabolism, and elimination of most of the antidepressants. Polypharmacy may act to induce or inhibit the metabolism of substrate medication that the patient is currently using. A comprehensive list of cytochrome P450 interactions is provided. Generally the antidepressants display similarity in efficacy; however, effectiveness may be substantially different among and within antidepressant pharmacotherapeutic classes. The pharmacotherapeutic selection of antidepressants is a multifactorial cognitive process, including consideration of medication side effects and adverse effects and patient-specific factors. Other factors in this selection process include drug interaction potential, patient's prior drug response, and both the patient's concomitant pathology and pathophysiology and pharmacotherapy-mediated events. In conjunction with age-related, gender-related, and genetic factors, a full description of current serotonin pharmacotherapy-mediated events is provided. Included in this article are a review of traditional and newer antidepressants, their pharmacokinetics, their pharmacodynamics, and an elaborate interaction focus. Special emphasis is focused on individual antidepressants and class of antidepressants. This article provides comprehensive insights in perception, recognition, treatment, and the selection process involving antidepressants.

Age of Onset↗

PubMedDate not supplied

Analgesics and osteoarthritis: are treatment guidelines reflected in clinical practice?

Osteoarthritis (OA) treatment is complex and multifactorial, with pharmacological regimens requiring sufficient flexibility to be adapted to individual disease progression, flare ups, and response to treatment. Coexisting conditions are common and can lead to problems regarding polypharmacy. Several guidelines have been published for the management of OA pain. While differences exist, most recommend paracetamol as the initial oral drug for OA, based on its efficacy, tolerability, and cost; in patients who respond inadequately to paracetamol, supplementary or replacement analgesics should be recommended. This article considers the reality of analgesic use for OA in clinical practice and the extent to which guidelines are followed both in primary and secondary care. An international survey of rheumatologists (n = 610) found that paracetamol was recommended as first-choice analgesic for OA by 82% of those surveyed. Similarly, in a survey of French GPs, 90% of those surveyed recommended paracetamol first line; NSAIDs were recommended more frequently for stronger pain relief but were also recommended alongside paracetamol as a first-line treatment of mild to moderate pain by 43% of GPs. Finally, a UK patient survey, conducted at a London hospital (n = 200), found that 64% of patients were taking more than 1 drug for treatment of painful OA of the knee or hip; 76% were taking paracetamol and 40% were taking an NSAID. A further 39% had used an NSAID in the past but switched treatment, primarily due to side effects. These findings reinforce the case for the simple analgesic paracetamol to be seen as the cornerstone of pharmacological OA treatment, both as a first-line analgesic and as a foundation to which additional treatment modalities, including NSAIDs, can be added if and when necessary.

Acetaminophen↗

PubMed2002

Comprehensive geriatric assessment: making the most of the aging years.

The elderly population is the most rapidly growing segment of our population. This group utilizes the highest proportion of medical care of any age group. Comprehensive geriatric assessment involves the evaluation of the physical, psychosocial and environmental factors that impact on the well-being of older individuals. The use of an organized approach with objective measurements helps target key areas of functional status. Important areas include the evaluation of activities of daily living, cognition, mood, social supports, gait and falls, nutrition, sensory impairments, incontinence, polypharmacy, elder abuse, pressure sores, pain, and advance directives. The provision of primary and secondary prevention is also increasingly important for older individuals. The components of a successful geriatric assessment program are outlined, with suggestions to improve compliance.

Activities of Daily Living↗

PubMed2004

Prevention of food-drug interactions with special emphasis on older adults.

PURPOSE OF THE REVIEW: Adverse drug interactions may be the fourth leading cause of death in hospitalized patients. In children and older adults undetected food-drug interactions may lead to serious morbidity and mortality and be misdiagnosed as chronic disease progression. Recent recognition of the effects of certain foods on many drugs metabolized by CYP450 families or drugs susceptible to chelation and adsorption have increased awareness for prevention of food-drug interactions. RECENT FINDINGS: Polypharmacy, self-medications with non-prescription drugs including herbal remedies, dietary/nutritional supplements, fortified foods, and polymorphism in drug metabolism increase the need to consider food-drug interactions. Improved food processing and analysis have led to overall decreased risk in monoamine oxidase inhibitor regimens with counseling. Drugs may create submarginal nutrient deficiencies with serious consequences, such as diuretics contributing to thiamin deficiency and further cardiac failure. Foods may contain compounds that lead to therapeutic failure, such as calcium-fortified foods producing therapeutic failure and promoting resistance in antibiotic therapy. Poor nutritional status can lead to poor health outcomes. SUMMARY: Prevention of adverse events from food-herb-drug interactions requires clinical monitoring in high-risk regimens and populations. Nutritional status has an important impact on the quality of life as well as appropriate responses to drug therapy. Both diet-drug histories and counseling are needed. As new foods and drugs emerge and more self-medication is promoted, research in the prevention of food-drug interactions is needed.

Aged↗

PubMedDate not supplied

Development of novel anticancer agents in older patients: pharmacokinetic, pharmacodynamic, and other considerations.

The development of novel anticancer agents in older patients presents both challenges and unique opportunities. Intrapatient variability due to comorbid conditions and the use of multiple concomitant medications may overshadow other age-related differences in pharmacokinetics. The increasing interest in oral agents may be especially problematic in older patients who have difficulty with adherence, particularly if the oral agents are given in combination or according to complex schedules. Polypharmacy, chronic comorbid conditions, and impaired organ reserve in the elderly can lead to pharmacodynamic differences such as increased toxicity and, possibly, reduced efficacy. Hampered immune responsiveness is an important area warranting further research. The development of novel agents to treat older patients with cancer cannot be successfully accomplished without increasing the proportion of elderly patients entered into clinical trials. Furthermore, data obtained from studies in older patients may provide valuable information applicable to the development of novel agents in younger patients and to a better understanding of cancer biology and treatment in general.

Aged↗

PubMed2003

Ziprasidone for dementia in elderly patients: case review.

Treatment of elderly patients with dementia-related behavioral disturbances and depression-related psychosis poses a significant problem, considering patients' frailty and use of polypharmacy for comorbid medical disorders. This case series describes the use of ziprasidone, a novel atypical antipsychotic, in three frail, elderly patients admitted to the hospital for behavioral disturbances secondary to dementia-related illness after their current treatment failed to improve symptoms or produced intolerable side effects. At admission, none of the patients were taking medications contraindicated for use with ziprasidone. In each case, ziprasidone resolved symptoms of agitation, psychosis, depression, and cognitive impairment sufficiently to permit discharge on maintenance therapy to assisted-living facilities or nursing homes. No patient suffered syncope or postural hypotension during treatment with ziprasidone. Electrocardiograms taken on admission and after institution of ziprasidone disclosed minimal increases in the QTc interval or no change from baseline, and no patient had a QTc interval > 500 ms. No drug-drug interactions occurred. Similar results were observed in an additional 53 of 62 elderly patients (aged 64-92 years) admitted to our institution. This experience suggests that ziprasidone is a safe and effective treatment option in elderly individuals who require antipsychotic medication.

Journal Article↗

PubMedDate not supplied

Cardiac drug and psychotropic drug interactions: significance and recommendations.

Understanding cardiac drug interactions with concurrent psychotropic prescriptions is essential for the practicing cardiologist, primary care physician, and psychiatrist. There has been an explosion in the use of new drugs in both psychiatry and cardiology without widespread knowledge of their potential interactions. The increasing tendency toward polypharmacy, the use of psychotropic medications by cardiologists and primary care physicians caring for cardiac patients, and the growth of the aging population present major challenges for the practitioner. Finally, there is a need to have models and paradigms for predicting potential drug interactions-the cytochrome P450 schema. This article describes a method to identify, understand, and codify the interactions between psychotropic and cardiac drugs, a systematic approach for updating this key database, and specific cardiac-psychotropic drug interactions. Specifically, this paper 1) details the interactions, 2) addresses the level of their clinical significance, 3) describes the potential mechanism(s) of the interactions, and 4) offers recommendations to the clinician (Appendix). Because the majority of the original clinical trials, either for cardiac medications or for psychotropic drugs, did not include studies comparing these two drug domains contemporaneously, their interactions often become known only with their combined use in the clinical arena, using the patient as "guinea pig" and through subsequent reporting.

Animals↗

PubMed2006

Management of neuropathic pain: translating mechanistic advances and evidence-based research into clinical practice.

The concept of rational polypharmacy is now well established in the field of pain management. This concept has evolved in concert with progress in understanding the pathophysiologic mechanisms of pain diseases and disorders and how medications affect these processes. Other clinical factors must be considered in formulating the pain management strategy most likely to succeed in both controlling pain and improving function in a given patient. This article will review how pain diagnosis, pain mechanisms, pain phenomenology, medication efficacy, and risk profile influence medication selection in pain medicine practice, with a selective focus on the treatment of neuropathic pain. In addition, the role of psychosocial factors as they affect pain management will be discussed.

Algorithms↗

PubMed2003

Impact of dyslipidemia in end-stage renal disease.

Heart disease is a major cause of morbidity and mortality among patients with renal failure. Premature atherosclerotic coronary heart disease is driven by multiple risk factors, including dyslipidemia and oxidative stress. In the nondialysis population, there is overwhelming evidence that treatment of dyslipidemia can significantly improve cardiovascular outcomes. Accumulating data indicate that dialysis patients have atherogenic lipid abnormalities. Although LDL cholesterol (LDL-C) levels in patients who undergo hemodialysis are normal or near normal, increased oxidized LDL-C, triglycerides, and lipoprotein (a) [Lp(a)]; decreased HDL cholesterol (HDL-C); and triglyceride-rich VLDL have been noted. Patients who receive peritoneal dialysis have a more atherogenic lipid profile with increased LDL-C, apolipoprotein B, oxidized LDL-C, triglycerides, and Lp(a) and decreased HDL-C. Furthermore, the LDL particles of peritoneal dialysis patients are small and dense. However, there is a dearth of information regarding the goals, efficacy, and safety of dyslipidemia treatment among dialysis patients. Given the strong evidence of risk reduction and the benefits of lipid-lowering treatment in the nondialysis population, the emerging consensus is that dialysis patients should be treated aggressively for dyslipidemia to an LDL-C goal below 100 mg/dl. Although physicians and patients may be reluctant to add medications because of concerns about polypharmacy, potential decreased compliance, and increased cost, the use of agents such as sevelamer that can serve multiple functions, including phosphate control, lipid lowering (decreased LDL-C and total cholesterol), and anti-inflammatory effects (decreased high-sensitivity C-reactive protein), should be explored and considered for patients who would benefit from such treatment.

Coronary Disease↗

PubMedDate not supplied

Lower gastrointestinal bleeding in elderly patients.

Lower gastrointestinal bleeding (LGIB) is one of the common medical emergencies that can become life-threatening in elderly patients. Increased prevalence of cerebrovascular and cardiovascular diseases, malignancy, polypharmacy, and the use of nonsteroidal anti-inflammatory drugs in elderly patients adversely affects the outcome of LGIB. Diverticular bleeding, vascular ectasia, polyps and hemorrhoids are among the common causes of LGIB in the elderly. In a majority of cases, LGIB stops spontaneously with resuscitation and supportive therapy. In those elderly patients in whom LGIB continues, benefits of endoscopic, angiographic, or surgical intervention should not be withheld because of age alone. However, the timing of tests and the type of intervention should be custom tailored for frail elderly patients. Such a decision should depend upon functional status, its impact on outcome, and the consent process.

Age Distribution↗

PubMedDate not supplied

If it is not cough, it must be dysgeusia: differing adverse effects of angiotensin-converting enzyme inhibitors in the same individual.

Presented is an unusual case of a 66-year-old-resident of a long-term care facility, who manifested severe dysgeusia and impaired quality of life attributed to the angiotensin-converting enzyme (ACE) inhibitor enalapril; not realized at the time was the fact that he had an adverse reaction-cough-just weeks earlier from another ACE inhibitor in the same class, quinapril, thus illustrating different adverse effects to two antihypertensives in the same class. Cough and dysgeusia are symptoms that may be easily overlooked as side effects of medications. As polypharmacy is common in nursing home settings, health care providers need to be vigilant about adverse drug reactions which are common, but preventable and often reversible.

Aged↗

PubMed2006

Cannabis use improves retention and virological outcomes in patients treated for hepatitis C.

OBJECTIVES: Despite the widespread use of polypharmacy, the management of hepatitis C virus (HCV) treatment-related side-effects is often incomplete, and many patients turn to cannabis for symptom relief. Unfortunately, there are few data about cannabis use on treatment outcomes, leaving clinicians without the data needed to inform recommendations. METHODS: To define the impact of cannabis use during HCV treatment, we conducted a prospective observational study of standard interferon and ribavirin treatment in 71 recovering substance users, of whom 22 (31%) used cannabis and 49 (69%) did not. RESULTS: Seventeen of the 71 study patients (24%) discontinued therapy early, one cannabis user (5%) and 16 non-users (33%) (P=0.01). Overall, 37 patients (52%) were end-of-treatment responders, 14 (64%) cannabis users and 23 (47%) non-users (P=0.21). A total of 21 out of 71 (30%) had a sustained virological response: 12 of the 22 cannabis users (54%) and nine of the 49 non-users (18%) (P=0.009), corresponding to a post-treatment virological relapse rate of 14% in the cannabis users and 61% in the non-users (P=0.009). Overall, 48 (68%) were adherent, 29 (59%) non-users and 19 (86%) cannabis users (P=0.03). Although cannabis users were no more likely than non-users to take at least 80% of the prescribed interferon or ribavirin, they were significantly more likely to remain on HCV treatment for at least 80% of the projected treatment duration, 95 versus 67% (P=0.01). CONCLUSIONS: Our results suggest that modest cannabis use may offer symptomatic and virological benefit to some patients undergoing HCV treatment by helping them maintain adherence to the challenging medication regimen.

Adolescent↗

PubMed2006

Weight change and antiepileptic drugs: health issues and criteria for appropriate selection of an antiepileptic agent.

BACKGROUND: Antiepileptic drugs (AEDs) constitute a diverse class of agents with heterogeneous mechanisms of action and diverse side-effect profiles. Weight change, either gain or loss, is a common AED side effect, conferring multiple risks of additional morbidity. REVIEW SUMMARY: The risks inherent in weight change, such as diabetes, coronary heart disease (CHD), and polycystic ovary syndrome (PCOS), may be exacerbated by the interaction of polypharmacy and comorbidities. Patients with epilepsy are more likely to be receiving multiple medications and are also more likely than the general population to suffer from morbidities related to both weight gain and weight loss. For certain patients, use of an AED associated with weight change, particularly weight loss, may be salubrious, although long-term weight change in these patients may ultimately become undesirable. Appropriate selection of an AED to minimize the risk of morbidity arising from weight change should be guided by a knowledge of patients' weight status, their comorbidities, and use of other medications. The potential for added risk in certain subpopulations, such as pediatric, elderly, and female patients, requires additional caution in selecting an AED. CONCLUSIONS: Use of a weight-neutral AED is recommended to lessen the risk of dysfunction arising from weight change.

Age Factors↗

PubMed2006

Determinants of first- and second-generation antipsychotic drug use in clinically unstable patients with schizophrenia treated in four European countries.

The present study investigated the use of antipsychotics in a sample of clinically unstable patients with schizophrenia who were recruited in four European sites. The study aimed: (i) to test whether the length of previous antipsychotic exposure was associated with the choice of antipsychotic medication; (ii) to test whether the severity of illness was associated with the use of second-generation antipsychotic agents (SGAs) or with the concomitant use of both first-generation antipsychotics (FGAs) and SGAs; and (iii) to investigate differences between study sites. Participants were recruited from patients under the care of psychiatric services serving geographical catchment areas in Croydon (UK), Verona (Italy), Amsterdam (The Netherlands) and Leipzig (Germany). Clinically unstable patients with a clinical diagnosis of schizophrenia and a research diagnosis of schizophrenia, established using the Item Group Checklist of the Schedule for Clinical Assessment in Neuropsychiatry, were enrolled. Sociodemographic and clinical data, including current antipsychotic drug therapy, psychopathology, adherence, insight, side-effects, attitudes towards medication and quality of life, were gathered. Three hundred and ninety patients were analysed in total. Almost 60% received SGAs, less than one-third FGAs, and less than 15% received both drug classes. Those receiving SGAs were younger and with a shorter length of antipsychotic drug therapy, whereas those receiving both drug classes were more often separated or widowed, unemployed and with a long history of antipsychotic drug therapy. The distribution of patients receiving FGAs, SGAs and both drug classes by illness-related variables showed that patients receiving both drug classes were more severely ill and complained of more side-effects. Using patients receiving FGAs as the reference category, multinomial logistic regression analysis showed that the length of antipsychotic treatment was negatively correlated with receiving SGAs, and that the severity of illness and being separated/widowed were positively correlated with receiving both drug classes. Compared with patients in Leipzig, patients in Amsterdam, Croydon and Verona were less frequently treated with SGAs and with combinations of both drug classes. Consistent with current clinical uncertainty with respect to what pharmacological treatment should be provided, patients with a long history of antipsychotic exposure were receiving FGAs, SGAs and combinations of both drug classes. Physicians tended to reserve polypharmacy for difficult-to-treat patients (i.e. for managing situations where, despite the lack of an evidence base, there is a pressing need to provide clinical answers).

Adolescent↗