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Compatibility of nitroglycerin, diazepam and chlorpromazine with a new multilayer material for infusion containers.

The stability and compatibility of three drugs: nitroglycerin, diazepam and chlorpromazine, with a new multilayer infusion bag were studied. The study was carried out comparatively with PVC bags with which these drugs are incompatible. The drugs were diluted in 5% dextrose or in 0.9% sodium chloride isotonic solutions. Solutions were stored during 8 or 48 h with or without any protection against light. Remaining concentrations of drug were determined by high-performance liquid chromatography (HPLC) during the storage. The admixtures were also monitored for precipitation, color change and pH. Whatever the isotonic solution used, the loss of drugs is in discredit of the use of PVC bags for their storage. So, these three drugs would not be stored in PVC bags. In multilayer bags, no loss of drugs and no color change were detected throughout the storage period. pH values were stable during the same storage period. These three drugs were compatible with multilayer bags in all tested conditions for 8 or 48 h. The leaching of the plasticizer di-(2-ethylhexyl) phthalate (DEHP), that is incorporated into PVC to make the bags soft and pliable was not detected in the three drug solutions during storage period. Our study confirms that these three drugs are incompatible with PVC bags, on the contrary the new materiel tested was proved to be interesting for drug storage.

Biocompatible Materials↗

Hyperlipoproteinemia in chronic renal failure: pathophysiological and therapeutic aspects.

Dyslipidemia of chronic renal failure is of multifactorial origin. Decreased activity of lipoprotein lipase and hepatic triglyceride lipase, peripheral insulin resistance, hyperparathyroidism and L-carnitine deficiency are the contributing factors. This results in a disturbed catabolism of chylomicron, accumulation of very-low-density (VLDL) and intermediate-density (IDL) lipoproteins as well as incompletely cleared remnant particles, whereas low-density lipoprotein (LDL) levels are diminished. There is current debate as to whether cardiovascular disease is accelerated and whether hyperlipidemia should specifically be treated. In addition, there have been few means of influencing these metabolic alterations. Drug incompatibility and consequently side effects render treatment difficult. The drugs that have been most tested for lipid lowering in chronic renal failure are the fibric acids. By their mode of action, they are the logical choice. Dose reduction overcomes major side effects such as myopathy and rhabdomyolysis. The second generation of fibric acid derivatives (gemfibrozil and beclobrate) show several advantages over formerly used derivatives. Treatment with lovastatin and simvastatin appears to be safe and is recommended in a minority of patients with predominantly elevations of LDL. HMG-CoA reductase inhibitors also lower remnant particles effectively in hemodialysis (HD) patients. L-Carnitine and low-molecular-weight heparin have been shown to influence VLDL rich in triglycerides in a subset of patients on HD. In posttransplant hyperlipidemia, diet remains the first course of action in all patients. When this approach fails, the new lipid-lowering agents, especially fibric acids, appear to be safe in short-term studies in azathioprine- and ciclosporin-treated patients. Lovastatin has been shown to be safe in stable renal transplant patients. Its toxicity seems to depend mainly on high ciclosporin whole blood through or plasma levels.

Humans↗

Evaluation of physicochemical incompatibilities during parenteral drug administration in a paediatric intensive care unit.

Patients in paediatric intensive care units (PICU) often receive numerous medications by the parenteral route. Frequently two or more drugs are delivered simultaneously through the same line and the risk of physicochemical incompatibilities is thus important. The objectives of this study were 1) to identify prospectively the combinations of injectable drugs administered in the PICU of our university hospital and 2) to analyze them according to information found in the literature. The data were collected by a pharmacist over a 30-day period and classified in three categories: compatible, incompatible and undocumented. Nineteen patients were included in the study with a median age of 3.2 years. The mean number (+/- SD) of injectable drugs per patient and per day was 6.5 (+/- 2.8), for a total of 26 drugs and 7 solutes. 64 combinations of drugs were observed with 2 (31.3%), 3 (45.3%), 4 (10.9%) or 5 (12.5%) drugs. 81 drug-drug and 94 drug-solute combinations were recorded. Among these, 151 (86.3%) were compatible, 6 (3.4%) incompatible and 18 (10.3%) undocumented. The incompatibilities included furosemide (Lasix), a drug in alkaline solution and Vamina-Glucose, a total parenteral nutrition solution. No clinical consequences resulting from drug incompatibilities were shown in this study. We suggest that in vitro compatibility tests on standard drug combinations, as well as a training program for nurses on drug incompatibility problems would sensitively increase the security of parenteral drug administration.

Adolescent↗

The influence of food on the absorption and metabolism of drugs.

Food-drug interactions can lead to a loss of therapeutic efficacy or toxic effects of drug therapy. Generally, the effect of food on drugs results from a reduction in the drug's bioavailability; however, an alteration in drug clearance can occur due to the effect of certain foods on drug metabolism. The proportion of adverse drug reactions due to food-drug interactions is not known and unfortunately only when a serious adverse drug reaction follows a food-drug interaction does the matter usually receive any significant attention. In order to improve therapeutic efficacy and to help prevent adverse drug reactions, it is necessary that clinicians be knowledgeable of the important food-drug incompatibilities and risk factors related to the increased likelihood of developing an adverse drug reaction due to food-drug interactions.

Biological Availability↗

[Individualized drug therapy--need for improvement].

The lack of dose adjustment to the individual needs of a patient is a major cause for the substantial difference between the efficacy of therapies established in large trials and the therapeutic results obtained in everyday practice (reduced effectiveness). In addition, these differences affect drug safety and ultimately also costs. Hence strategies to maintain good compliance and to avoid incompatibilities, drug interactions and adverse events should be applied whenever drugs are prescribed. This supplement compiles different techniques and measures which may support health professionals in reaching these goals.

Dose-Response Relationship, Drug↗

Survey of drug use practices and antibiotic prescribing pattern at a general hospital in Nigeria.

OBJECTIVE: To describe the current drug use practices at the institution, and gather baseline data, which can serve as a basis for designing an appropriate intervention to improve the drug use profile. METHOD: A retrospective audit of in- and out-patient prescriptions, generated during the period January-March 1999. Indicators of drug use pattern include: average number of drugs prescribed per encounter (ANDPE), average number of antibiotics prescribed per encounter (ANAPE), % encounter with antibiotics (PEA), percent of antibiotic prescriptions based on microbial sensitivity test results (MCST). Additionally, a "knowledge, attitude and practice" (KAP) survey of prescribers and dispensers was performed. Indicators of prescribing and dispensing quality include: sources of drug/prescribing information, availability and use of the hospital formulary, knowledge of the prescribing process and the adequacy of the drug supply management system. RESULTS: A total of 9984 outpatient prescriptions and 127 in-patient case notes were audited. The total number of prescribers and dispensers surveyed were 88 and 13 respectively. The ANDPE was found to be 3.16 for out-patients and 9.7 for in-patients, ANAPE was 1.1 and 2.4 for out-patients and inpatients respectively. The PEA was 50.3% for out-patients and 96.7% for in-patients. Only 4.2% of in-patient antibiotic prescriptions were based on MCST and percent encounter with switches in antimicrobial therapy was 52.1% while the average number of switches per encounter was 1.35. In 18.5% of the in-patient encounters there was evidence of drug incompatibilities. The KAP survey revealed that prescribers and dispensers in the hospital rely on different sources for their drug information needs (MIMS vs Martindale Extrapharmacoepia). None of the prescribers surveyed was able to correctly enumerate all the 4 steps involved in the prescribing process, about 25% got at least 2 steps correctly, and only 9.1% of the dispensers surveyed could accurately define a hospital formulary. The drug supply management system was found to be inadequate. CONCLUSION: The survey revealed that appreciable gaps in knowledge with respect to rational drug use, still exists among these cadre of healthcare professionals. The foregoing suggests an urgent need for review of current policies and systems in the hospital with the view of enhancing the drug use practices of the health providers. Specifically it is recommended that there should be an intervention program involving concerted continuing education (to influence the KAP of the various cadre of healthcare providers) and the establishment of a hospital formulary/standard treatment guidelines.

Adolescent↗

[Detection of levamisole and ivermectin in organ samples from a dead collie].

A collie, known for its breed-dependent adverse reaction to ivermectin, was without any clinical signs. The dog was prophylactically treated with 3 mg/kg KG (s.c.) of levamisole. Within 15 minutes, the dog showed convulsions, vomitus, and dyspnea, and perished 2.5 hours after injection of the drugs. The pathological findings were not informative as to the cause of death, and with regard to the adverse reactions, additional application of ivermectin was not excluded. Therefore, organ samples were submitted for toxicological analysis of both levamisole and ivermectin. For detection of levamisole and ivermectin, modified GC/MS and HPLC procedures were developed. Concentrations up to 535 micrograms levamisole and up to 26 ng ivermectin were found per g tissue. Both analytical methods are sensitive enough to detect these drugs after application of low doses. This study elucidates that combination of low-dosed ivermectin and levamisole is no recommendable means against adverse effects of ivermectin, with respect to collies. Moreover, the synergistic effects of ivermectin and levamisole suggests the same drug incompatibility in other dog breeds and animal species.

Adipose Tissue↗