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PubMed2000

Position of Dietitians of Canada and the American Dietetic Association: Nutrition intervention in the care of persons with human immunodeficiency virus infection.

Human immunodeficiency virus (HIV) targets the immune system, making an infected person susceptible to infection and neoplasm because of an impaired ability to mount an adequate immune response. Malnutrition and its complications can further render an HIV-infected person susceptible to opportunistic infection, reduce effectiveness of and increase tolerance to medications and other therapies. Though effective antiretroviral treatments have dramatically reduced death rates in Canada and the United States, HIV-infected individuals are faced with a lifetime of vigilant polypharmacy to control HIV and associated complications. Malnutrition, various forms of tissue wasting, fat accumulation, increased lipid levels, and risk of additional chronic disease have become central issues in health care plans. Nutrition evaluation and medical nutrition therapy (MNT) should be an integral part of the ongoing health care of persons with HIV disease to address these multiple factors that can contribute to health decline. Medical nutrition therapy involves both the assessment and appropriate treatments to maintain and optimize nutritional status. Nutrient-based treatment may include diet therapy, counseling, or the use of supplemental nutrition (oral, enteral, and/or parenteral delivery of nutrients). Symptoms that threaten nutritional status may require both dietary and medication interventions. Metabolic alterations that result in malnutrition may require additional therapies to achieve optimal nutritional status such as hormonal and inflammatory modulation.

Journal Article↗
PubMed2001

In human therapy, is the drug-drug interaction or the adverse drug reaction the issue?

In recent years, many publications in scientific journals have reported, in healthy volunteers, potential food-drug or drug-drug interactions. The lay press has frequently emphasized such interactions and extrapolated on the dangers of food-drug or drug-drug interactions. However, the clinical relevancy of these interactions has not always been substantiated in patients. The aim of the present review was to assess the clinical relevancy of drug-drug interactions occurring at the level of the biotransformation of the drug. For this purpose, the incidence of serious, life-threatening adverse drug reactions (ADRs) of drugs metabolized by different enzymes of cytochrome P450 found in the safety reports issued in megatrials were compared with those from placebo trials. It was concluded that serious ADRs secondary to drug-drug interactions are infrequent; drug-drug interactions including selected drugs with a narrow therapeutic index and eliciting life-threatening undesired effects occur; and serious ADRs secondary to drug-drug interactions are most frequent in elderly patients, in the presence of polypharmacy, in the psychiatric patient population, and in the presence of inappropriate prescriptions and of multiple prescriptors.

Adverse Drug Reaction Reporting Systems↗
PubMed2001

[Isolated systolic hypertension in the elderly].

Isolated systolic hypertension is the most common type of hypertension in the elderly. A number of trials have widely shown that it is an independent risk factor for cardiovascular morbidity and mortality. This review focuses the prevalence of isolated systolic hypertension, its pathophysiology, diagnosis and treatment. The optimal treatment strategy is to maximize reduction in systolic blood pressure and to minimize reduction in diastolic blood pressure. All classes of antihypertensive agents can be used, but calcium antagonists, ACE-inhibitors and, more recently, the angiotensin II antagonists appear to be more successful in improving large artery stiffness and therefore are especially useful in treating isolated systolic hypertension in the elderly. A careful evaluation and treatment has to be made in particular in those patients with more risk factors, in order to choose the most appropriate drug and to avoid dangerous drug-drug interactions where polypharmacy occurs.

Adrenergic beta-Antagonists↗
PubMed2001

[Severe accidental hypothermia in an elderly woman].

Profound hypothermia (core temperature of less than 28 degrees C) is a life threatening state and a medical emergency associated with a high mortality rate. The prognosis depends on underlying diseases, advanced or very early age, the duration prior to treatment, the degree of hemodynamic deterioration, and especially, the methods of treatment, including active external or internal rewarming. This is a case study of an 80-year-old female patient with severe accidental hypothermia (core temperature 27 degrees C). She was found in her home lying immobile on the cold floor after a fall. The patient was in a profound coma with cardiocirculatory collapse, and the medical staff treating her was inclined to pronounce her deceased. On her arrival at the hospital, she was resuscitated, put on a respirator and actively warmed. Very severe metabolic disorders were found, including a marked metabolic acidosis composed of diabetic ketoacidosis (she had suffered from insulin treated type 2 diabetes mellitus) and lactic acidosis with a very high anion gap (42) and a hyperosmotic state (blood glucose 1202 mg/dl). There were pathognomonic electrocardiographic abnormalities, J-wave of Osborn and prolonged repolarization. Slow atrial fibrillation with a ventricular response of 30 bpm followed by a nodal rhythm of 12 bpm and reversible cardiac arrest were recorded. The pulse and blood pressure were unobtainable. Despite the successful resuscitation and hemodynamic and cognitive improvement, rhabdomyolysis (CKP 6580 u/L), renal failure and hepatic damage developed. She was extubated and treated with intravenous fluids containing dopamine, bicarbonate, insulin and antibiotics. Her medical condition gradually improved, and she was discharged clear minded, functioning very well and independent. Renal and liver tests returned eventually to normal limits. Progressive bradycardia, hypotension and death due to ventricular fibrillation or asystole commonly occur during severe hypothermia. Respiratory and metabolic, sometimes lactic, acidosis, lethargy and coma, hypercoagulopathy, hyperosmolar state, acute pancreatitis and renal and hepatic failure are frequent complications of hypothermia. Underlying predisposing causes of hypothermia are diabetic ketoacidosis, cerebrovascular disease, mental retardation, hypothyroidism, pituitary and adrenal insufficiency, malnutrition, acute alcoholism, liver damage, hypoglycemia, sepsis, hypothalamic dysfunction, sepsis and polypharmacy, and especially, the use of sedative and narcotic drugs. Our case demonstrates once again that CPR once begun should continue until the successful rewarming because "no one is dead until warm and dead".

Aged↗
PubMed1999

Geriatric screening in acute care wards--a novel method of providing care to elderly patients.

OBJECTIVE: To assess a nurse-implemented geriatric screening system. DESIGN: Descriptive study. SETTING: University teaching hospital, Hong Kong. PATIENTS: All (5080) elderly patients admitted between 1 January 1996 and 31 December 1996. MAIN OUTCOME MEASURES: Patient characteristics such as disease, prior admission, living quarters, and regular medications; interventions taken; and morbidity and mortality. RESULTS: The most common interventions were referral to a convalescent hospital, patient education, and carer contact. The overall death rate was 8.5% and the diseases with the highest mortality rates were renal failure, liver cirrhosis, and cancer. Approximately one quarter of patients had been admitted to hospital in the previous month. The death rate was higher among women than men (10.8% versus 6.7%, P<0.001; odds ratio=1.68; 95% confidence interval, 1.38-2.05), as was the percentage of those with a history of admission in the previous month (32.8% versus 20.0%, P<0.001; odds ratio=1.95; 95% confidence interval, 1.71-2.21). Patients with multiple pathologies and polypharmacy had a greater frequency of previous 1-month admission compared with those who did not have these features (37.5% versus 20.0%, P<0.001; odds ratio=2.37; 95% confidence interval 2.0-2.7). Patients living in old-age homes had a higher death rate and more previous 1-month admissions than home dwellers, and patients living in private old-age homes had a higher death rate but lower number of previous 1-month admissions than those living in subsidised old-age homes. CONCLUSIONS: This study has collected important data from one form of integrated geriatric practice, which can be used for future service provision.

Journal Article↗
PubMed2002

Evaluating and treating unintentional weight loss in the elderly.

Elderly patients with unintentional weight loss are at higher risk for infection, depression and death. The leading causes of involuntary weight loss are depression (especially in residents of long-term care facilities), cancer (lung and gastrointestinal malignancies), cardiac disorders and benign gastrointestinal diseases. Medications that may cause nausea and vomiting, dysphagia, dysgeusia and anorexia have been implicated. Polypharmacy can cause unintended weight loss, as can psychotropic medication reduction (i.e., by unmasking problems such as anxiety). A specific cause is not identified in approximately one quarter of elderly patients with unintentional weight loss. A reasonable work-up includes tests dictated by the history and physical examination, a fecal occult blood test, a complete blood count, a chemistry panel, an ultrasensitive thyroid-stimulating hormone test and a urinalysis. Upper gastrointestinal studies have a reasonably high yield in selected patients. Management is directed at treating underlying causes and providing nutritional support. Consideration should be given to the patient's environment and interest in and ability to eat food, the amelioration of symptoms and the provision of adequate nutrition. The U.S. Food and Drug Administration has labeled no appetite stimulants for the treatment of weight loss in the elderly.

Aged↗
PubMed2002

OC144-093, a novel P glycoprotein inhibitor for the enhancement of anti-epileptic therapy.

Inhibitors of P gLycoprotein (Pgp) may be useful for the enhancement of blood-brain barrier penetration of anti-epileptic drugs (AEDs). Due to polypharmacy and the need for chronic treatment, Pgp inhibitors used in epilepsy should be highly specific and non-toxic. In particular, it may be essential to use compounds that produce minimal inhibition of enzymes involved in metabolism of AEDs and other drugs used by epilepsy patients. OC144-093 is a novel substituted diarylimidazole generated using the OntoBLOCK system, a solid-phase combinatorial chemistry technology, in combination with high-throughput cell-based screening. The compound is an extremely potent inhibitor of Pgp-mediated multidrug resistance (MDR) in cancer with an average FC50 of 32 nM, but does not inhibit multidrug resistance-associated protein (MRP1). OC144-093 is the least non-specifically toxic Pgp inhibitor described to date, with an average cytostatic IC50 of >60 microM in 15 cell types. It is not metabolized by cytochrome P450s CYP3A4, 2C8 or 2C9 enzymes involved in AED metabolism. OC144-093 does not produce a pharmacokinetic (PK) interaction with paclitaxel and has exhibited an excellent PK and safety profile in phase I clinical trials. Our results suggest that OC144-093 may represent an ideal candidate for use in enhancement of AED blood-brain barrier penetration.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

[Gabapentin in the treatment of epilepsy in the elderly].

INTRODUCTION: Epilepsy is the third most common neurological disease in the elderly. Diagnosis of epilepsy in this age is increasing because more people are reaching older age and physician awareness about this disorder is higher than in the past. Seizures are suspected in patients with episodic impairment of consciousness and neurological function, but in addition, seizures can be the cause of fluctuating cognitive derangement and nocturnal episodes of neurological dysfunction. DEVELOPMENT: The etiological spectrum of epilepsy in the elderly is different than in younger adults because of a higher prevalence of cerebrovascular disease and degenerative disorders of the central nervous system. The selection and dosage of antiepileptic drugs requires proper attention to special pharmacokinetic and pharmacodynamic situations that are common in older individuals. Changes that occur with advanced age are responsible of distinct pharmacokinetics, decreased tolerability to antiepileptic drugs, concomitant systemic diseases. In addition poor compliance and polypharmacy can complicate therapy. CONCLUSIONS: Gabapentin has favourable pharmacokinetic properties: lack of hepatic metabolism, no protein binding, and easy to calculate regimen for patients with renal failure. For these reasons is a good candidate drug for treatment of seizures in the elderly.

Acetates↗
PubMed2002

Management of cardiovascular risk in diabetic patients: evolution or revolution?

Diabetes is associated with a marked increase in the risk of cardiovascular disease. Epidemiological evidence shows that hyperglycemia, hypertension and disorders of both lipid and thrombosis are involved in the etiology of cardiovascular disease in diabetes. Intervention trials on each of such factors have demonstrated a favourable effect in terms of reduction of cardiovascular disease, suggesting that even in diabetic patients in whom blood glucose levels are adequately controlled, other cardiovascular risk factors, such as hyperlipidemia, hypertension and prothrombotic state, should be aggressively treated. The need for an aggressive treatment has been recently underscored by the UKPDS (United Kingdom Prospective Diabetes Study) researchers who suggest that "polypharmacy" is now needed for the prevention of diabetic complications, implying that this approach requires an adequate control of all cardiovascular risk factors even using associations of drugs for each of them. A thorough application of these concepts might appear difficult in particular when the resource cost is considered. However, it has been shown that blood glucose, blood pressure and serum lipid control are advantageous in diabetic patients not only in terms of cost/benefit ratio but also in terms of quality of life. In the present article, we will briefly review this evidence and discuss the ethical and socioeconomic concerns that may subsequently rise.

Cardiovascular Diseases↗
PubMed1979

The pharmacological treatment of epilepsy.

A short classification and brief clinical description of epileptic seizures are presented. The pharmacokinetic principles underlying modern drug treatment of epileptic seizures are discussed and the drug(s) of choice for different seizure types are listed according to their clinical efficacy. The current view of using single-drug therapy rather than polypharmacy, whenever possible, is emphasized.

Anticonvulsants↗
PubMed2002

Pain management in the elderly.

Pain in the elderly is often unrecognized and undertreated. Ineffective pain management can have a significant impact on the quality of life of older adults, leading to depression, social isolation, and a loss of function. Proper assessment of older adults requires the physician to regularly ask about the presence of pain and be skillful in assessment strategies to evaluate the frequency and intensity of pain. Assessment of pain in older adults with dementia and communication disorders is especially challenging. Effective pain management in elderly patients should include both pharmacologic and nonpharmacologic strategies. Pharmacologic strategies call for administration of nonopioid analgesics, opioid analgesics, and adjuvant medication. Polypharmacy, drug-drug and drug-disease interactions, age-associated changes in drug metabolism, and the high frequency of adverse drug reactions need to be carefully considered in using medications in this population. Nonpharmacologic approaches such as cognitive-behavioral therapy, education, osteopathic manipulative treatment, and exercise should be applied in addition to pharmacologic therapy. Using a team approach and incorporating principles of pain management can effectively provide good analgesia for older adults.

Acetaminophen↗
PubMed2002

Differential gene expression in rats following subacute exposure to the anticonvulsant sodium valproate.

Sodium valproate (VPA) is clinically employed as an anticonvulsant and, to a lesser extent, as a mood stabilizer. While the incidence of toxicity associated with the clinical use of valproate is low, serious hepatotoxicity makes up a significant percentage of these rare adverse effects, with fatalities occurring mainly in children receiving polypharmacy. Previous studies have highlighted the different pharmacological effects of acute valproate exposure, a combination of which are likely to underpin its observed broad-spectrum anticonvulsant efficacy. However, limited studies have been undertaken to investigate the subacute effects of this compound and how genomic effects may underlie the observed hepatotoxic effects. Investigation into the mild hepatoxicity observed in rats exposed to high doses of VPA may provide important information on the human situation. Male Sprague-Dawley rats were dosed with 500 mg/kg/day sodium valproate: after necropsy, mRNA was subjected to suppression PCR subtractive hybridization, identifying 8 up-regulated and 14 down-regulated mRNA species. The down-regulation of several mRNA species coding for enzymes involved in cellular energetics (e.g., succinate dehydrogenase, aldolase B) was of particular interest, as mitochondrial dysfunction is a key feature of valproate hepatotoxicity. In vitro studies were then undertaken to examine the dose and time dependence of these changes and also their effect on the overall energy levels within the cell. We demonstrate that, both in vivo and in vitro, valproate exposure in rats results in a significant decrease in pathways involved in cellular energy homeostasis. These changes may provide insight into the rare human hepatoxicity associated with this compound.

Animals↗
PubMed2002

[Psychological intervention and heart failure: from theory to clinical practice].

The management of chronic heart failure patients is complicated by the presence of multiple comorbid conditions, polypharmacy, psychosocial concerns and difficulties with adherence to complex medication, dietary regimen, smoking cessation and correct physical activity. Taken together, these factors contribute to the persistently high hospitalization and mortality rates as well as to the poor quality of life of these patients. In fact the progressive worsening of symptoms such as fatigue, breathlessness, anxiety and depression may have a negative impact on the patient's quality of life. Nevertheless a psychological intervention may contribute positively to enhance functional capacity and quality of life, and potentially to improve survival in patients with heart failure. On the basis of our experience and the scientific literature, we describe in this paper a psychological program for such patients. The psychometric tests used in the assessment, the psychological interventions to improve emotional reactions and the educational programs for disease management are analysed.

Female↗
PubMed2002

Treatment options in pediatric epilepsy syndromes.

Recent evidence suggests that various epilepsy syndromes respond differently to antiepileptic drugs. It follows that a more precise diagnosis, together with a better understanding of AED mechanisms of action, enables them to be used more specifically, and therefore more effectively. Patient characteristics including age of onset, seizure frequency, EEG data and the findings of imaging studies, provide diagnostic pointers which enable the physician to reach a syndrome diagnosis and to choose the most appropriate AED for the individual patient. Home videotapes of paroxysmal events are becoming increasingly available and are often of great assistance. Parents should be encouraged to record their children's attacks. Careful history-taking and correct interpretation of clinical data remain the cornerstones of accurate diagnosis and successful treatment. However, the specificity of antiepileptic drugs is relatively limited and often pharmacotherapy should start using an agent with a broad spectrum of activity appropriate for the primary seizure type. It is in fact common that several antiepileptic agents have similar or identical effectiveness for one particular form of epilepsy. Therefore, the eventual side effects and the greater or lesser difficulties in handling the drug play an essential role in the choice of a therapeutic agent. Polypharmacy should be avoided and surgery should be considered early for selected patients, particularly children, who fail to respond to an appropriate drug trial. Correct diagnosis and the first drug(s) used may have a crucial impact on the evolution of given epilepsy. One major emphasis in the management of epilepsy is on information that should be complete, adapted to the level of understanding, and objective, although given in a positive manner. The understanding and cooperation of children and their families is clearly decisive for the success of therapy, and this requires a confident relationship between the physician and the patient. Current knowledge, on antiepileptic drugs options in paediatric epilepsy syndromes, is discussed.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

[Neutropenia in a patient treated with clozapine in combination with other psychotropic drugs].

Clozapine is an atypical antipsychotic known for its efficacy in refractory schizophrenia. However, according to different epidemiological studies clozapine can induce neutropenia in less than 3% of patients and may represent a major problem for the management of treatment-resistant patients not responding to conventional or other atypical antipsychotics. Recently, a few case of neutropenia have been reported following the addition of other medications to clozapine, notably paroxetine, risperidone, trimethoprim-sulfamethoxazole and erythromycin. In our report we present the case of Mr A., a 40-year-old Caucasian patient with a 20-year history of paranoid schizophrenia. After numerous trials with conventional antipsychotics, partial remission of psychotic symptoms was obtained with clozapine. Over the past eight years during his treatment with clozapine, the patient presented 2 episodes of neutropenia. The first episode came five years after starting clozapine and was attributed to the addition 6 weeks earlier of haloperidol (2 mg/day) to clozapine (250 mg/day) and divalproex (1,500 mg/day). Recently, one week after the addition of risperidone (2 mg/day) to clozapine (550 mg/day), leukocytes count dropped from 12 100/mm(3) to 5 700/mm(3) and neutrophils from 7 400/mm(3) to 900/mm(3). The patient was also taking haloperidol (4 mg/day), methotrimeprazine (35 mg/day), procyclidine (5 mg/day) and valproic acid (1,500 mg/day). Twelve days after discontinuation of risperidone, leukocytes and neutrophils count increased to 11,100/mm(3) and 6,300/mm(3) respectively while the treatment with clozapine was continued. The first eighteen weeks of treatment represent the period where the risk of neutropenia is the highest. In our patient neutropenia occurred 5 and 7 years after starting clozapine. It is proposed that the two neutropenic episode were precipitated by adding respectively haloperidol and risperidone to clozapine. Also, divalproex can potentially cause a decrease in white blood cell count and may have contributed to the two neutropenic episode. It is suggested that drug interactions may be responsible for neutropenia in clozapine treated patients and that clozapine should not necessarily be discontinued in the presence of neutropenia. Also we propose that hematological surveillance should be done on a weekly basis for 4 to 6 weeks following the addition of psychotropic drugs known for their potential to cause neutropenia when associated with clozapine. Therefore polypharmacy may contribute to cause neutropenia in clozapine treated patients and that discontinuation of an antipsychotic should be done before introducing another one.

Adult↗
PubMed2003

Postmortem oxycodone and hydrocodone blood concentrations.

There is limited data on postmortem oxycodone concentrations, consisting of three published reports with a total of 11 cases, many of which were polypharmacy cases. This report presents the results of a review of autopsy and coroner's reports from 10 counties for the years 2000 and 2001 to locate cases with oxycodone or hydrocodone exposure as a leading cause of death. Eighty-eight cases were located. Twenty-four deaths were attributed to oxycodone alone. Mean and median postmortem oxycodone blood concentrations were 1.23 mg/L and 0.43 mg/L, respectively. The range was 0.12 to 8.0 mg/L, with 13 cases (54%) < or = 0.5 mg/L. Seventeen deaths were attributed to hydrocodone alone. Mean and median postmortem hydrocodone blood concentrations were 0.53 mg/L and 0.40 mg/L, respectively. The range was 0.12 to 1.6 mg/L, with 11 cases (65%) < or = 0.5 mg/L. There were seven cases where the cause of death was attributed to the effects of a combination of hydrocodone and oxycodone. Mean oxycodone and hydrocodone blood concentrations were 0.34 mg/L and 0.14 mg/L, respectively. Forty cases involved polysubstance overdoses with significant involvement of other drugs and ethanol. Mean oxycodone and hydrocodone blood concentrations were 0.18 mg/L and 0.29 mg/L, respectively. The list of other substances involved was extensive but included ethanol, amitriptyline, methadone, codeine, propoxyphene, and acetaminophen. The findings of this study report oxycodone values associated with a fatality at blood concentrations lower than previously reported. This may represent enhanced information because of the larger sample group. Hydrocodone values associated with a fatality were similar to previously published values.

Adult↗
PubMed2003

[Summary of the Dutch College of General Practitioners' practice guideline 'Delirium in elderly people'].

The Dutch College of General Practitioners' practice guideline 'Delirium in elderly people' contains a number of key messages. These are: Consider the diagnosis of delirium in the case of changes in consciousness and attention, incoherent thinking or disorientation, if this picture developed over a short period of time (hours to days) and if the symptoms vary over the 24-hour period. Delirium is provoked by one or more somatic disorders; investigation and treatment of these disorders is an essential part of managing delirium. It is often difficult to distinguish delirium from dementia and depression. Although delirium is generally reversible, the prognosis in the elderly is relatively poor. If delirium is accompanied by fear or agitation, haloperidol is the drug of first choice, but in delirium induced by alcohol withdrawal or benzodiazepine withdrawal, a short-acting benzodiazepine such as lorazepam or oxazepam is indicated. Part of the treatment, but also prevention of delirium is focused on inducing factors that can provoke a delirium, such as medication with an anticholinergic effect, polypharmacy, inadequate nutrition, dehydration, sleep deprivation, immobility and sensory handicaps.

Aged↗
PubMed2003

[Are the Danish Society of General Practitioners' clinical guidelines concerning "Identification and investigation of dementia and dementia-like conditions" useful as the basis of dementia investigation in general practice?].

INTRODUCTION: During the last five years better possibilities have appeared for investigation and medical treatment of dementia. Society and the national health authorities have a growing demand for systematical identification of dementia. In 1999, DSAM published a clinical guideline for identifying dementia. The aim of the study was to test the usefulness of that guideline. MATERIAL AND METHODS: A total of 22 out of 29 general practitioners (GPs) agreed to use the guidelines of the Danish Society of General Practitioners (DSAM) and the questionnaires from three consultations in order to systematically identify dementia. At the same time, the GPs gave their opinion about the usefulness of the guidelines. RESULTS: A total of 22 GPs sent results from 69 patients. A group of 49 patients had been CT-scanned, 13 patients had been examined by neuropsychologists, and nine patients had started acetylcholinesterase inhibitor treatment. CONCLUSION: Some GPs found it embarrassing to offer dementia identifying to their patients. Identifying dementia was complicated and time-consuming. Identifying dementia offered opportunities to look further into polypharmacy and cooperation with other health sectors. Necessary but not sufficient preconditions for starting identifying dementia in general practice will be fees, direct admission to CT-scanning and neuropsychologist, and possibly right to prescribe acetylcholinesterase inhibitors. The conclusion was that all GPs found the guidelines of DSAM useful for identifying dementia in general practice.

Adult↗