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Results for “Polypharmacy”

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PubMed1989

Pseudoephedrine accumulation in renal failure.

Neuropsychiatric complications, such as metabolic encephalopathy, are common occurrences in end-stage renal disease (ESRD) patients. Frequently, metabolic encephalopathy develops in relationship to the multiple pharmacologic therapies routinely employed in this population. Such polypharmacy often leads to adverse drug reactions, drug-drug interactions, or dosage error. In this regard, over-the-counter (OTC) medications are commonly perceived as being "somewhat benign" when, in fact, their potential for adverse effect may be significant. The authors describe the course of a 64-year-old hemodialysis patient who became intoxicated on conventional doses of pseudoephedrine only to regain neurologic integrity upon discontinuation of the medication.

Ephedrine↗

PubMed1997

Pharmacologic treatment of lower urinary tract dysfunction in geriatric patients.

Medications to treat lower urinary tract dysfunction in older adults are selected to alter specific physiologic parameters. Pharmacotherapy alone results in modest clinical improvement. Because of the high prevalence of adverse drug reactions and polypharmacy in the geriatric population, medication should be used for those conditions that do not respond sufficiently to behavioral therapy. For stress incontinence, medications with alpha-adrenergic agonist properties are the mainstay of pharmacotherapy because they increase outlet resistance. Pharmacotherapy of urinary frequency and urge incontinence aims to decrease detrusor irritability and increase bladder capacity by inhibiting cholinergic stimulation of the bladder. In addition to these medications, in postmenopausal women, estrogen seems to have an additive effect for both urge and stress incontinence. More randomized, placebo-controlled, double-blinded clinical trials are needed that compare various pharmacologic agents and combinations, as well as pharmacotherapy with other forms of treatment for lower urinary tract dysfunction.

Adrenergic alpha-Antagonists↗

PubMed2000

Nondepolarizing neuromuscular blockers inhibit the serotonin-type 3A receptor expressed in Xenopus oocytes.

UNLABELLED: Molecular cloning and sequence comparison indicates a high degree of structural homology between muscle nicotinic acetylcholine (nACh) and serotonin-type 3 (5-HT(3A)) receptors, both members of the direct ligand-gated family of ion channels. Because of the structural similarities and common evolutionary origin of these receptors, neuromuscular blockers (competitive nACh antagonists) may demonstrate pharmacologic cross talk and exhibit attributes of 5-HT(3A) receptor antagonists. We examined six clinically-used neuromuscular blockers for their ability to antagonize currents flowing through the 5-HT(3A) receptors in voltage clamped Xenopus oocytes. The neuromuscular blockers reversibly inhibited the 5-HT(3A) receptor-gated current in the rank order potency of (IC50 mean +/- SEM): d-tubocurarine (0.046 +/- 0.003 microM), atracurium (0.40 +/- 0.03 microM), mivacurium (15.1 +/- 2.93 microM), vecuronium (16.3 +/- 2.24 microM), and rocuronium (19.5 +/- 2.31 microM). Gallamine was essentially inactive as a 5-HT(3A) receptor antagonist with an extrapolated IC50 of 1170 microM. We demonstrate that drugs classically known as competitive nACh receptor antagonists also block 5-HT(3A) receptors. It is likely that certain neuromuscular blockers share pharmacological properties with 5-HT(3A) receptor antagonists, such as a reduction in postoperative nausea and vomiting. With careful drug selection, pharmacological cross talk could potentially be used to minimize polypharmacy and optimize patient management. IMPLICATIONS: Muscle nicotinic acetylcholine and serotonin-type 3A (5-HT(3A)) receptors are similar. Therefore neuromuscular relaxants may block 5-HT(3A) receptors. Our pharmacological study demonstrates that neuromuscular relaxants, as with ondansetron, are 5-HT(3A) receptor antagonists. It is likely that certain neuromuscular relaxants exhibit ondansetron-like clinical properties, such as reduction in postoperative nausea and vomiting.

Animals↗

PubMed2005

Treatment-refractory schizophrenia.

PURPOSE OF REVIEW: The aim of this article is to critically review the current literature on treatment-refractory schizophrenia with an emphasis on emergent themes and key findings. RECENT FINDINGS: New information continues to emerge on the impact of each second-generation antipsychotic on the treatment-refractory patient population and on the traditionally more difficult-to-treat components (e.g. cognition, suicidality, violence) of the illness. There are continued efforts with pharmacogenetics to predict response and side-effect risk with antipsychotic medications. Polypharmacy continues to be a major and poorly understood treatment practice. SUMMARY: Our field is advancing the therapeutic nuances of therapy with second-generation antipsychotics in treatment-refractory schizophrenia. Additionally, there is a growing appreciation of the emergent adverse-effect profile of antipsychotic medications and these risk-benefit considerations are more pronounced in severely ill patients.

Journal Article↗

PubMed2001

Paradoxical relations of drug treatment with mortality in older persons.

Medication use patterns provide popular surrogate measures of disease, yet selective under-use of drugs by elderly patients with potentially unmeasured comorbidity may lead to artifactual "protective" associations between use of specific drugs and mortality. We examined the relation between use of 20 common classes of drugs and mortality among the 129,111 residents of New Jersey 65-99 years of age who had at least one hospitalization during the years 1991-1994 and filled prescriptions through either Medicaid or that state's Pharmacy Assistance for the Aged and Disabled program. Each study drug class was used by more than 5,000 subjects during the 120 days before hospitalization; 41,930 subjects died in the hospital or during the year after discharge. Users of drugs from each of seven therapeutic classes had reduced age- and sex-adjusted rates of death relative to non-users: lipid-lowering agents, nonsteroidal anti-inflammatory agents, beta blockers, thiazides, glaucoma drugs, calcium channel blockers, and anti-anxiety drugs. Adjustment for comorbidity and polypharmacy had little effect on these results. We found similar results in a separate nonhospitalized cohort of 132,071 elderly persons. Much of this observed association appears to be nonetiologic. These findings raise concerns about using observational studies in high-risk populations to infer associations between drug use and outcomes.

Age Factors↗

PubMed1993

Retrospective study of drug response in 87 patients with progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is a progressive neurodegenerative disease that responds poorly to pharmacologic intervention despite its clinical, neurochemical, and pathologic similarity to Parkinson's disease. We reviewed our experience with drugs used in the treatment of patients with PSP who were followed in the Department of Neurology, University of Medicine and Dentistry of New Jersey--Robert Wood Johnson Medical School. Of 136 patients identified, adequate drug-response data were available for 87 (64%). Benefit and adverse effects of therapy were graded on a 4-point scale: 0, none; 1, minimal; 2, moderate; 3, marked. The three most frequently used drugs were amitriptyline (32% of patients benefited), imipramine (28% of patients benefited) and levodopa/carbidopa (Sinemet) (38% of patients benefited). Levodopa/carbidopa, amantadine, selegiline, and amitriptyline gave the best risk/benefit ratios. Monotherapy tended to show more benefit and fewer adverse effects than polypharmacy.

Amitriptyline↗

PubMedDate not supplied

Combined use of risperidone and olanzapine in the treatment of patients with resistant schizophrenia: a preliminary case series report.

Polypharmacy, or the use of multiple drugs in the therapy of psychiatric disorders, is not recommended. However, appropriate combinations of pharmacologic mechanisms may enhance the efficacy of antipsychotic drugs and alter the course of schizophrenia. In recent years, some articles have been published about the successful use of clozapine and risperidone in combination for the treatment of patients with resistant schizophrenic and schizoaffective disorders. However, safety of this drug combination is open to discussion. This report presents the results of a preliminary study of five patients with resistant schizophrenia successfully treated with risperidone-olanzapine combination. The results suggest that this combination may be useful. In the future, the efficacy of risperidone-olanzapine combination should be confirmed in larger study populations before its clinical application is considered.

Adult↗

PubMed1989

The concurrent use of lithium and methylphenidate in a child.

The case of a young boy with symptoms of both attention deficit and affective disorders is presented. The patient was successfully treated with a combination of lithium and methylphenidate. Issues about comorbidity and polypharmacy in children are raised, and the concommitant use of lithium and methylphenidate in a child is discussed.

Attention Deficit Disorder with Hyperactivity↗

PubMed1997

Case study: adverse response to clonidine.

The use of clonidine alone and in combination to treat a variety of problems has increased in child and adolescent patients. Four cases of adverse experiences with clonidine are described. Clinical guidelines for the use of clonidine in particular and the use of polypharmacy in general are presented.

Adrenergic alpha-Agonists↗

PubMed1986

Suspected adverse methylphenidate-imipramine interactions in children.

Two cases are presented which illustrate the dangers inherent in utilizing a polypharmacy approach in treating children with psychotropic medication. In each case, severe adverse effects, including cognitive and mood deterioration, were experienced by the child when treated with a combination of methylphenidate and imipramine. Possible mechanisms at the neurotransmitter level are described as postulated determinants for this pharmacological interaction.

Adolescent↗

PubMed1996

Bipolar mood disorder: practical strategies for acute and maintenance phase treatment.

The chronic, complex, and episodic course of bipolar mood disorder presents a formidable challenge to the clinician making a treatment plan. Although numerous therapeutic agents are reported to be efficacious for one or more aspects of bipolar illness, treatment is seldom completely effective and is never curative. The goal of treatment is to modify the symptomatic expression of the illness with the result that fewer, briefer, and milder episodes occur. In pursuit of this goal, the use of multiple medications, polypharmacy, is the rule rather than the exception. This article offers recommendations for treatment strategies based on the phase and stage of the illness. The strategies are organized into algorithms that emphasize the use of mood-stabilizing medications as initial steps in a systematic, iterative approach to treatment. Practical issues related to the use of mood-stabilizing therapies are discussed.

Acute Disease↗

PubMed1996

Cytochrome P450 enzymes: interpretation of their interactions with selective serotonin reuptake inhibitors. Part II.

The SSRIs have been used as an example to show how one might interpret the available evidence to draw conclusions about the relationships between drugs and P450s. Under what circumstances might one apply the knowledge of such relationships? First, the clinical implications must be considered when drugs with a narrow therapeutic index are coprescribed with other drugs that may affect P450s. For example, good clinical practice demands that before a TCA is coprescribed with another drug, the physician be aware of the potential for the second drug to interact with CYP2D6. Second, it may be helpful to consider P450 enzymes when adverse events occur during polypharmacy. It may happen that a known side effect of one drug occurs. Rather than attributing this to patient sensitivity, the physician should consider the possibility that a pharmacokinetic drug interaction increased plasma drug concentration, which in turn enhanced the probability of such an occurrence. Even when a pharmacokinetic drug interaction is considered as a possible cause, an appreciation of the role of P450s may lead to the realization that an interaction was not only possible but that it was likely. Finally, copharmacy can be used intentionally to produce controlled interactions. Indeed, planned pharmacokinetic drug interactions at the level of P450s have been proposed to reduce cyclosporine dosage requirements, to reduce variability of TCA levels, and to manipulate the contribution of alternative metabolic pathways to minimize toxic effects. As long as pharmaceuticals are metabolized by the P450 system, interactions with the various isozymes will be inescapable. It is fortunate that understanding them is becoming more tractable.

1-Naphthylamine↗

PubMed1999

The prescribing of psychotropic drugs by primary care physicians: an international collaborative study.

Psychotropic drugs play a major role in primary care management of mental disorders. This study expands the existing data on prescribing practices using data from a 15-center, primary care epidemiologic survey. Questions to be addressed include the following: Which clinical and nonclinical factors are related to the prescribing of psychotropic drugs by primary care physicians? How do prescribing patterns vary across primary care centers? At each center, primary care patients were screened using the General Health Questionnaire, and a stratified random sample completed a standardized diagnostic assessment. For each patient completing the diagnostic assessment, the treating primary care physician provided data on clinical diagnosis and medications prescribed. Study results indicated that 11.5% of all practice attenders, 51.7% of cases who received a diagnosis of mental disorders by a physician, and 27.6% of cases who received a diagnosis using the Composite International Diagnostic Interview were treated with psychotropic medication because of their psychologic problems. Anxiolytics, hypnotics, and antidepressants each accounted for approximately 20% of all prescriptions. Prescription rates increased with the prominence of psychologic complaints, severity of mental disorder, severity of social disability, female gender, age older than 40 years, lower education, unemployment, and marital separation. Rates and type of drugs also varied among specific mental disorders; 19.3% of patients with brief recurrent depression but 55.0% with agoraphobia got any psychotropic drug. Antidepressant drugs were prescribed in 7.7% of anxiety disorders compared with 31.9% of depressive disorders. There were large differences between international centers. When comparing client-type centers with clinic-type centers, overall prescription rates were similar (51.2 vs. 52.9%), but significant differences were observed with respect to psychotropic polypharmacy (12.6% client, 6.3% clinic), tranquilizer medication (24.2 client, 32.9% clinic), and antidepressant medication (17.3 client, 8.9% clinic). Psychotropic drugs have an important role in the treatment of mental disorders by general practitioners. Prescription is associated with a number of clinical but also nonclinical factors that must be recognized when guidelines for international use are to be published. Recognition of mental disorders and selection of specific drug classes are important areas in which medical practice needs improvement.

Adult↗

PubMed1991

The elderly depressed and treatment with fluvoxamine.

Depression is highly prevalent in the elderly and there are difficulties with definition and diagnosis. The signs and symptoms of depression may differ from those in younger patients since the elderly are frequently preoccupied with physical ailments and may have more agitation, insomnia and hypochondriasis. The aetiology and cause of depression and its association with psychosocial and other risk factors are discussed, with particular reference to masked depression, depressive delusional illness and 'pseudo dementia'. A range of treatments have been used in depressive patients, including psychotherapy, cognitive therapy, ECT and various drug treatments. In the elderly drugs may cause more problems than in younger patients. These can be divided into those associated with: pharmacokinetics, polypharmacy, side effects, dosage and lethality. Trials of antidepressants in the elderly are discussed and include trials with tricyclic antidepressants, monoamine oxidase inhibitors and SSRIs. Particular reference is made to a trial of fluvoxamine versus mianserin in the elderly, which demonstrated that fluvoxamine is as effective as mianserin in treating depression, and has fewer side effects.

Aged↗

PubMed2003

Amantadine as augmentation therapy in the management of treatment-resistant depression.

Treatment-resistant depression is an important clinical problem presenting a major challenge to clinical psychiatry. While several strategies have been attempted, including medication switch, antidepressant polypharmacy and various augmentative regimens, success remains limited. Amantadine (AMN), an agent traditionally used in the treatment and prophylaxis of influenza, is now known to exhibit prominent effects at the level of dopaminergic, monoamine oxidase and N-methyl-D-aspartate systems. The present reports on the efficacy of AMN as augmentation to standard antidepressant treatment in patients with treatment-resistant depression. Eight patients with treatment-resistant depression consented to receive AMN, titrated up to a dose of 300 mg, over a period of 4 weeks in a non-blinded fashion. Improvement in both depression and anxiety scores were observed from week 1, with patients exhibiting improvement of depressive scores of up to 49% by study completion. Females appeared to exhibit a stronger response, and within a shorter period of time. Side-effects reported included dry mouth and sedation. AMN appears to demonstrate efficacy as a safe and effective augmentative agent in treatment-resistant depression. Further studies are clearly mandated to test these preliminary observations in a double-blinded manner.

Adult↗

PubMedDate not supplied

A framework for studying the nutritional health of community-dwelling elders.

BACKGROUND: Ensuring nutritional health for elders has been shown to reduce healthcare costs and enhance quality of life. Studies, however, have shown that malnutrition is present in 2% to 51% of community-dwelling elders, depending on the definition used and the population studied. An empirically tested framework for studying nutritional health in community-dwelling elders is not yet available. OBJECTIVE: To test the goodness-of-fit exhibited by the framework of nutritional health among community-dwelling elders based on the Roy Adaptation Model using structural equation modeling (SEM). METHODS: A population-based study investigated 243 elders dwelling in public housing. Demographics, polypharmacy, chronic illness, oral health, depressive symptoms, functional status, and satisfaction with social support were assessed to test their relation with nutritional health according to the propositions of the Roy Adaptation Model and scientific evidence. RESULTS: The SEM analysis indicated that functional status, oral health, depressive symptoms, and satisfaction with social support affect nutritional health directly. Oral health, depressive symptoms, functional status, and satisfaction with support mediated the effects of age, ethnicity, education, and number of medications and chronic illnesses on nutritional health. The model accounted for 35% of the variance in nutritional health and demonstrated a good fit with the data and with the values for Bentler's Comparative Fit Index (0.94) and chi (1.76). CONCLUSIONS: The propositions of the Roy Adaptation Model were supported, and the findings showed that this framework of nutritional health among community-dwelling elders could serve as a theoretical and empirical base for future inquiry.

Activities of Daily Living↗

PubMed1984

Sleep disorders among psychiatric outpatients.

Mental health clinics, particularly the ones serving middle-aged and elderly patients, are usually confronted with serious problems of insomnia, which could trigger or aggravate physical or emotional ailments. It could also lead to drug dependence or contribute to polypharmacy. In this study, we have attempted to make a profile of the insomniacs of a VA Mental Hygiene Clinic and to correlate several variables found in common among the patients. Our work indicated that certain drugs such as benzodiazepines were more effective than others. It also indicated that certain types of insomnia, such as that with frequent awakenings, were more amenable to treatment.

Ambulatory Care↗

PubMed1998

Non-steady state population kinetics of intravenous phenytoin.

This observational study explored the effects of demographics, sickness, and polypharmacy on the non-steady state population pharmacokinetics of intravenous phenytoin. One hundred fifteen patients were studied. Models were developed using the NONMEM program with hybrid first-order conditional estimation. A Michaelis-Menten model with delayed induction was preferred over a Michaelis-Menten model without induction, a Michaelis-Menten model with immediate induction, or a linear model with delayed induction. When the data were fit to a Michaelis-Menten model with delayed induction, the volume of distribution (Vd) was found to depend on weight and serum albumin. The Vd was estimated to be 0.95 l/kg, assuming an albumin level of 3 g/dl. The Michaelis-Menten constant (km) was estimated to be 7.9 mg/l. The baseline maximum metabolic rate was 580 mg/day for a 70-kg patient. The average time to onset of induction was 59.5 hours. If a fever developed after induction began, it increased the extent of induction. This model was evaluated retrospectively in 26 additional patients, yielding a mean prediction error of -0.4 mg/l (-3.0-2.2 mg/l) and a mean absolute prediction error of 4.7 mg/l (3.2-6.2 mg/l) based on two-level feedback. Given the large interindividual variances in maximum metabolic rate, phenytoin levels should be measured frequently.

Aged↗