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PubMed2005

[Pharmacological treatment of osteoarthritis in the elderly].

Osteoarthritis (OA) is the most common cause of functional disability in the elderly. Pain and loss of motion induce a vicious circle, leading to instability, frailty and ultimately invalidity. Currently, there is no treatment to reverse or slow the disease progression to a clinically meaningful extent. Thus, the primary goal of OA treatment in the elderly is pain relief and preservation of joint function. For this, pharmacological, non-pharmacological and if necessary surgical treatment regimes must form an integrated concept. However, the real challenge is polymorbidity and other age-related or age-associated factors, which influence the course of disease and its therapy unfavorably. The changes in pharmacokinetics and -dynamics in the elderly can be compensated for the nonopioid and opioid-analgesics by the well known "start low, go slow" approach. More problematic are non-steroidal anti-inflammatory drugs (NSAIDs), which are most often used for symptomatic treatment of OA: Patients over 65 have an enhanced susceptibility to the gastrointestinal and renal side effects of NSAIDs; all NSAIDs, not only coxibs, increase the cardiovascular risk in patients with such a disease; number and severity of drug interactions is elevated due to age-associated polypharmacy. Thus, NSAIDs, including coxibs, should be used with great caution for treatment of OA in the elderly.

Aged↗

PubMed2002

Weight gain and glucose and lipid metabolism disturbances during antipsychotic medication: a review.

Antipsychotic medication is the mainstay of treatment for functional psychotic illnesses. However, for some patients weight gain and the disturbances in blood-lipid levels and glucose balance associated with their use are significant disadvantages, and pose health risks that may affect prognosis. A substantial body of evidence suggests that weight gain is at least partly related to the blocking effects of antipsychotic medication on serotonin- and histamine-mediated neurotransmission. The disadvantages associated with weight gain can be reduced by an appropriate choice of antipsychotic and avoidance of polypharmacy, by regular monitoring of the patient's weight, and, if necessary, by the patient's participation in a dieting programme.

Antipsychotic Agents↗

PubMed2000

Gastrostomy buttons for nutritional support in children with cystinosis.

Poor growth in children with cystinosis may be a combination of sub-optimal nutritional intake, gastrointestinal dysfunction and polypharmacy. We report our experience with gastrostomy buttons (GBs) in five children (4 male) with cystinosis treated at a median age of 3 years (range 1.4-8.8 years). All children received overnight GB feeding for a mean duration of 27 months (range 7-42 months). During 135 patient-months of observation, the mean life of the GB was 5.7 months (range 3-7.7 months), with a mean of 3.4 GB changes (range 1-6) per patient. An average of five (range 3-7) medications were administered daily via the button. The mean energy intake achieved was 118% of the estimated average requirement (range 86%-183%), with 58% of total energy and 55% of protein intake being delivered via the GB during the study period. Mean height standard deviation score (SDS) was -3.79 at the start of GB feeding and -3.08 at the end of the study period, with mean weight SDS of -3.79 and -2.17 (P=0.042), respectively. The buttons have been welcomed by the families and should be considered as a treatment option for providing the nutritional prescription and administering medications.

Child↗

PubMed2006

Symptom clustering in advanced cancer.

A major goal of palliative medicine is to control symptoms that interfere with quality of life. Identification of symptoms that occur together (cluster) may aid in symptom management, resulting in greater therapeutic benefit to the patient. An analysis of 25 symptoms from 922 patients with advanced cancer was undertaken to determine if symptom clusters could be identified. Cluster analysis was done using an agglomerative hierarchical method with average linkage; the absolute value of the correlation between pairs of symptoms was used as the measure of similarity. A correlation of >or=0.68 was used to define the final clusters. Seven clusters were identified: (1) fatigue: anorexia-cachexia; (2) neuropsychological; (3) upper gastrointestinal; (4) nausea and vomiting; (5) aerodigestive; (6) debility; (7) pain. Recognition of symptom clusters should help understand symptom pathophysiology and target therapies that perhaps can be used to relieve multiple symptoms in that cluster. This could result in improved quality of life for patients with advanced cancer and perhaps reduce polypharmacy, lessen drug side effects, and have pharmacoeconomic benefits.

Adolescent↗

PubMed2006

PRN sedation-patterns of prescribing and administration in a child and adolescent mental health inpatient service.

OBJECTIVE: To identify utilisation rates of prn (pro re nata) sedation in children and adolescents receiving inpatient psychiatric treatment, and to compare correlates of prn prescribing and administration. METHOD: A retrospective chart review examined 122 medical charts from a child and youth mental health inpatient service. RESULTS: 71.3% of patients were prescribed prn sedation and 50.8% were administered prn sedation. Patients received an average of 8.0 doses of prn sedation, with 9.8% receiving 10 or more doses. Chlorpromazine and diazepam were the most commonly utilised agents. Prescribing of prn sedation was only related to use of regular medications (p < 0.01), and non-parent carers (p < 0.01). In contrast, administration of prn sedation was associated with multiple diagnoses (p < 0.01), pervasive development disorder (p < 0.01), mental retardation (p < 0.01) ADHD (p < 0.01), longer hospital admission (p < 0.01), use of atypical antipsychotics (p < 0.01) and polypharmacy (p < 0.01). CONCLUSIONS: Despite lack of data to inform practice, prn sedation is widely utilised, especially in complex patients. Future research in this area needs to incorporate nurses and examine whether patients benefit from prn sedation, which drugs and dosing patterns optimise safety and efficacy, and what is the role of prn sedation in the context of other medication.

Adolescent↗

PubMed2000

Stimulant drugs.

Stimulants are a key element in the treatment of ADHD. Carefully designed trials of stimulants have found substantial improvement in ADHD core behaviours in 65-75 % of subjects with ADHD. Most standard stimulants are rapidly absorbed, with their behavioural effects appearing within 30 minutes, reaching a peak within one to three hours and disappearing within five hours. Doses at school are often necessary, in spite of the risk of peer ridicule and added adult supervision requirements. The mechanism by which stimulants act to reduce hyperactivity is not completely understood, but they improve impulsivity and activity levels. Several controlled evaluations made over periods of time greater than a year show a clear persistence of medication effects over time. A carefully crafted programme of treatment with methylphenidate is more effective in the reduction of hyperactivity symptoms than an intensive programme of behavioural and cognitive intervention. The combination of stimulants with psychosocial interventions in ADHD offers few advantages over medication alone. Unchallengeable guides to practice that would be appropriate everywhere are difficult to propose. It is imperative that clinicians prescribing stimulants should monitor the use of the drug properly, making sure that it is not being abused by the child's family, peers or those dispensing medication at school. Polypharmacy should only be embarked on by a specialist service and the combination of methylphenidate and clonidine should be used cautiously. Apart from ADHD, stimulants are useful in narcolepsy, resistant depression and partial syndromes of attention and hyperactivity. Major gaps in knowledge remain; pharmacokinetics, pharmacodynamics and pharmacogenetics of stimulant effects need further study. Details of stimulant administration regimes seem to have a major effect on the response achieved. Further research is needed, preferably in realistic practice settings, comparing different forms of combination with psychological interventions, investigating the effects in groups of children outside the core of schoolaged children with typical ADHD: preschool children, adults, those with partial syndromes (such as inattentiveness) and those with co-morbid disorders.

Adolescent↗

PubMed2006

Patients' attitudes towards and experiences of generic drug substitution in Norway.

OBJECTIVE: The aim of the study was to assess patients' attitudes towards and experiences of generic substitution 3 years after generic substitution of prescription medicines was permitted in Norway. METHODS: Prescriptions from 2,128 consecutive patients in a Norwegian pharmacy were retrospectively reviewed to identify all patients (n=274) receiving eight or more different prescription drugs on the fifth level in the Anatomical Therapeutic Chemical (ATC) classification system during the last 6 months. An age-adjusted control group (n=269) of patients receiving three to seven different prescription drugs was randomly selected. Of the 543 patients, 386 were eligible for inclusion. Both groups received a mailed questionnaire addressing their experiences with and attitudes towards generic substitution. RESULTS: The overall response rate was 73% (281/386) and the average age of the respondents was 66 years old. The study found that patients who reported to have received information from their physician or the pharmacy about generic substitution were more likely to have switched (P<0.001). About half (138/281) of the patients had experienced a generic switch, and a higher proportion of the polypharmacy patients had their medication substituted compared to the control patients (P<0.001). Altogether 50 (36%) of the patients who had experienced a switch, reported one or more negative experiences connected to the substitution, and 29 of these (21%) reported an overall negative experience after the change. The experiences of the patients were not related to age, gender, or number of medications or information about generics from either the pharmacy or the physician. About 41% of the patients would not switch if they had no personal economic incentives. CONCLUSIONS: About 1/3 of the patients who had their medication substituted reported negative experiences. Generic drug substitution for a number of patients is not considered an equal alternative to branded drugs, and these patients may need additional information and support. The lack of correlation between patient experiences and age, gender, and medical regimen complexity is interesting and should be investigated further.

Adolescent↗

PubMed2004

Liver-directed gene therapy for dyslipidemia and diabetes.

This article provides an update of liver-directed gene therapy for dyslipidemia, reviewing papers published since 2002 and summarizing progress in gene transfer vectors. Despite the availability of polypharmacy and other therapeutic interventions, the treatment of severe dyslipidemia remains a challenge and continues to be an important target for experimental gene therapy. Gene therapy strategies that focus on long-term therapeutic efficacy of different regimens are emerging from small animal experiments, and new therapeutic genes and/or new approaches have been developed. A novel strategy for gene therapy for diabetes was published recently. Gene therapy for dyslipidemia and diabetes is still in its infancy. Nonetheless, recent progress in this area is encouraging and bodes well for the future.

Diabetes Mellitus, Type 2↗

PubMed2004

Drugs that cause Torsades de pointes and increase the risk of sudden cardiac death.

Torsades de pointes (TdP) is a potentially life-threatening arrhythmia associated with not only antiarrhythmic drugs, but noncardiac drugs of many different classes. All these drugs prolong the QT interval by their blocking of the potassium channel I(Kr), and many are metabolized by the cytochrome P450 isoenzyme CYP3A4. Polypharmacy with other drugs utilizing the same enzyme, or inhibiting CYP3A4, can lead to TdP. A consistent finding of all the QT-prolonging drugs is predominance of TdP in women. Other risk factors for QT prolongation and TdP include hypokalemia, congestive heart failure, and structural heart disease. Knowledge of potential drug interactions and other risk factors for TdP can help in reducing the number of adverse events associated with the use of QT-prolonging drugs.

Anti-Arrhythmia Agents↗

PubMed2004

Combination therapy as first-line treatment for hypertension.

With the cut-off point between "normal" and "high" blood pressure (BP) being pushed increasingly downward, especially for patients with multiple cardiovascular risk factors, most hypertensives need more than one antihypertensive agent to reach their target BP. In this article, we examine the rationale for combining drugs from different classes that have synergistic or additive effects and properties that might offset one another's adverse hemodynamic and/or metabolic reactions. We suggest circumstances in which the initiation of therapy with a fixed two-drug combination might be preferable to the usual practice of starting with monotherapy followed by upward titration and addition of other agents, and we briefly review the existing fixed drug combinations. We end with the intriguing and provocative notion of the future "polypill," a fixed combination of agents addressing various components of the metabolic syndrome as well as other coexisting common risk factors in both high-risk patients with conditions requiring polypharmacy and in healthy, asymptomatic individuals.

Adrenergic beta-Antagonists↗

PubMed2002

Parkinson's disease: medical treatment of moderate to advanced disease.

Parkinson's disease, a common neurodegenerative disorder, results in significant morbidity 10 to 15 years after disease onset and increased mortality. Levodopa is the mainstay of therapy and provides benefit for the duration of the illness. However, within 5 years, up to 50% of individuals develop fluctuations, including dyskinesias, wearing off, and "on/off" effects. Optimal management of Parkinson's disease patients requires careful titration of medications, with use of polypharmacy, including levodopa, dopamine agonists, catechol-O-methyltransferase inhibitors, amantadine, and anticholinergics in order to maintain good motor function and quality of life. With advancing disease, problems such as dysphagia, dysarthria, and gait and balance abnormalities occur, which are not responsive to dopaminergic medication. Due to extradopaminergic neuronal system degeneration, autonomic dysfunction can also be prominent. Recognition and management of these problems is helpful in improving quality of life in late-stage disease. In very late stages, dementia may complicate treatment, requiring discontinuation of combination therapy and use of low-dose levodopa with atypical neuroleptics.

Amantadine↗

PubMed2003

Electroconvulsive therapy in the medically ill.

The use of electroconvulsive therapy (ECT) in the US continues to expand in the treatment of psychiatric disorders. Electroconvulsive therapy remains the "gold standard" for the treatment of major depression and a variety of other psychiatric and neurologic disorders. Because of the effectiveness and resurgence of ECT, more patients are considered good candidates for this treatment option. Overall, these patients are medication refractory and elderly, and thus more sensitive to polypharmacy. Additionally, these patients tend to have more coexisting medical problems, and often require that a practitioner have solid clinical knowledge of the fields of medicine and psychiatry. This article will review some of the most common comorbid conditions found in patients referred for ECT.

Aged↗

PubMed2004

Update on pharmacotherapy of borderline personality disorder.

Pharmacotherapy is a very common form of treatment for borderline personality disorder or its concomitant disorders. This paper reviews all the open-label and placebo-controlled trials of second generation medications studied in samples of well-defined borderline patients. Most of the medications studied in double-blind, placebo-controlled trials were efficacious. Most of these medications were also useful in treating symptoms of affective dysregulation and impulsive aggression, which have been suggested to be the core dimensions of psychopathology of underlying borderline personality disorder. Taken together, the results of these studies suggest that the choice of medication can be guided as much by tolerability and safety as by symptom presentation. It also suggests that the common practice of polypharmacy, which has no empiric support, may be unnecessary for most patients with borderline personality disorder.

Affect↗

PubMed2000

The use of psychotropics in the medically ill.

Underlying medical illness may present a challenge when prescribing psychotropic medications. Disease-related changes in pharmacokinetics and pharmacodynamics, as well as vulnerability to side effects, polypharmacy, and potential drug interactions are all important considerations. Successful treatment of psychiatric disorders may have a beneficial impact on medical morbidity and mortality, as well as quality of life. This article reviews the relevant considerations when using psychotropic medications in six major medical populations (cardiac, cerebral vascular, pulmonary, liver, renal, and seizure disorders).

Drug Interactions↗

PubMed2003

Atrial Fibrillation in the Elderly.

Atrial fibrillation (AF) is the most common sustained arrhythmia in adults, and its incidence and prevalence increase progressively with age. As a result, AF-associated morbidity and mortality increase with age. Therefore, because even asymptomatic AF markedly increases the risk of stroke and other embolic events, aggressive treatment is warranted in order to avoid the potentially devastating sequelae of this condition. Goals for the treatment of AF in the elderly population should primarily focus on alleviation of symptoms and prevention of strokes, while minimizing potential toxic effects of polypharmacy. Rate control should be optimized with atrioventricular (AV) nodal- blocking agents. The decision of anticoagulation should be individualized for each patient, balancing the risk of stroke against the risk for major bleeding complications. In elderly patients without symptoms, rate control and anticoagulation is the preferred method of treatment. Antiarrhythmic therapy to maintain sinus rhythm is generally reserved for patients with significant symptoms attributable to AF. However, simply maintaining sinus rhythm has not been proven to decrease stroke risk; therefore, long-term anticoagulation is recommended even in patients who are in sinus rhythm on antiarrhythmic drugs. AV nodal ablation with implantation of a pacemaker is a safe and excellent method of rate control for elderly patients who do not respond adequately to pharmacotherapy. Other invasive procedures, such as pulmonary vein isolation and Cox-Maze operations, are associated with high risks of complications in the elderly and are generally not recommended. Postoperative AF is common in the elderly population, and its development in high-risk patients should be anticipated and promptly treated to avoid potential hemodynamic compromise and prolonged hospitalization.

Journal Article↗

PubMed2002

Painful Peripheral Neuropathy.

Treatment of neuropathic pain is the primary focus of management for many patients with painful peripheral neuropathies. Neuropathic pain is a common feature of many peripheral neuropathies including those associated with diabetes, uremia, HIV infection, and alcohol abuse. Pain is also present in the majority of patients with idiopathic sensory and sensorimotor polyneuropathies. A growing number of pharmacologic agents are available for the treatment of neuropathic pain. The medications that have undergone the most rigorous study are the tricyclic antidepressants and anticonvulsants. These two families of medications are widely used and represent first-line agents in the management of neuropathic pain. Pain management should begin with a concerted effort to identify the etiology of the neuropathy, as directed therapy may help alleviate the symptoms. When initiating pharmacotherapy for neuropathic pain, one must individualize treatment and choose an agent that is likely to be tolerated, as adverse events are not uncommon for some of the medications. Treatment of neuropathic pain remains challenging, with considerable variability in an individual's response to the various agents and even to different drugs in the same class. However, monotherapy with a well-chosen agent or rational polypharmacy that combines medications with different mechanisms of action will benefit a majority of patients with neuropathic pain.

Journal Article↗

PubMed2006

Essential tremor: treatment options.

The treatment of essential tremor depends on the tremor severity, location, and risk benefit ratios. Mild to moderate tremor usually will respond to oral agents such as noncardiac selective beta-blockers or primidone. Other agents including ethanol, topiramate, benzodiazepines, gabapentin, levetiracetam, and zonisamide may be effective. There are very little data comparing different oral agents, but there is support for polypharmacy in some cases. Botulinum toxin injections are effective in some tremor patterns, especially wrist flexion/extension and head tremor. For severe tremor, surgical lesioning or deep brain stimulation of the thalamus is justified and often dramatically improves function.

Journal Article↗

PubMedDate not supplied

AF150(S) and AF267B: M1 muscarinic agonists as innovative therapies for Alzheimer's disease.

The M1 muscarinic agonists AF102B (Cevimeline, EVOXACTM: prescribed in USA and Japan for Sjogren's Syndrome), AF150(S) and AF267B--1) are neurotrophic and synergistic with neurotrophins such as nerve growth factor and epidermal growth factor; 2) elevate the non-amyloidogenic amyloid precursor protein (alpha-APPs) in vitro and decrease beta-amyloid (A beta) levels in vitro and in vivo; and 3) inhibit A beta- and oxidative-stress-induced cell death and apoptosis in PC12 cells transfected with the M1 muscarinic receptor. These effects can be combined with the beneficial effects of these compounds on some other major hallmarks of Alzheimer's disease (AD) (e.g. tau hyperphosphorylation and paired helical filaments [PHF]; and loss of cholinergic function conducive to cognitive impairments.) These drugs restored cognitive impairments in several animal models for AD, mimicking different aspects of AD, with a high safety margin (e.g. AF150[S] >1500 and AF267B >4500). Notably, these compounds show a high bioavailability and a remarkable preference for the brain vs. plasma following p.o. administration. In mice with small hippocampi, unlike rivastigmine and nicotine, AF150(S) and AF267B restored cognitive impairments also on escape latency in a Morris water maze paradigm in reversal learning. Furthermore, in aged and cognitively impaired microcebes (a natural animal model that mimics AD pathology and cognitive impairments), prolonged treatment with AF150(S) restored cognitive and behavioral impairments and decreased tau hyperphosphorylation, PHF and astrogliosis. Our M1 agonists, alone or in polypharmacy, may present a unique therapy in AD due to their beneficial effects on major hallmarks of AD.

Alzheimer Disease↗