The process of drug dispensing and distribution at four Brazilian hospitals: A multicenter descriptive study

A multicenter descriptive study was carried out in two steps: an interview with providers involved in the medication processes, and then non-participating observation of their environment and practices. Only one hospital was found to have a bar-coding, dispensing system connected to a computerized prescription system. fit all participating hospitals at least 90% of the drugs were dispensed and distributed as unit doses, but in none of them did pharmacists assess prescriptions. The study findings showed that the processes of drug dispensing and distribution in Brazilian hospitals encounter several problems, mostly associated to work environment conditions and inadequacy in drug ordering and requests.

Adverse drug events in an intensive care unit of a university hospital

Purpose Adverse drug events (ADEs) are harmful and occur with alarming frequency in critically ill patients. Complex pharmacotherapy with multiple medications increases the probability of a drug interaction (DI) and ADEs in patients in intensive care units (ICUs). The objective of the study is to determine the frequency of ADEs among patients in the ICU of a university hospital and the drugs implicated. Also, factors associated with ADEs are investigated. Methods This cross-sectional study investigated 299 medical records of patients hospitalized for 5 or more days in an ICU. ADEs were identified through intensive monitoring adopted in hospital pharmacovigilance and also ADE triggers. Adverse drug reactions (ADR) causality was classified using the Naranjo algorithm. Data were analyzed through descriptive analysis, and through univariate and multiple logistic regression. Results The most frequent ADEs were ADRs type A, of possible causality and moderate severity. The most frequent ADR was drug-induced acute kidney injury. Patients with ADEs related to DIs corresponded to 7% of the sample. The multiple logistic regression showed that length of hospitalization (OR = 1.06) and administration of cardiovascular drugs (OR = 2.2) were associated with the occurrence of ADEs. Conclusion Adverse drug reactions of clinical significance were the most frequent ADEs in the ICU studied, which reduces patient safety. The number of ADEs related to drug interactions was small, suggesting that clinical manifestations of drug interactions that harm patients are not frequent in ICUs.

Evaluation of three brands of drug interaction software for use in intensive care units

Objective To evaluate drug interaction software programs and determine their accuracy in identifying drug-drug interactions that may occur in intensive care units. Setting The study was developed in Brazil. Method Drug interaction software programs were identified through a bibliographic search in PUBMED and in LILACS (database related to the health sciences published in Latin American and Caribbean countries). The programs` sensitivity, specificity, and positive and negative predictive values were determined to assess their accuracy in detecting drug-drug interactions. The accuracy of the software programs identified was determined using 100 clinically important interactions and 100 clinically unimportant ones. Stockley`s Drug Interactions 8th edition was employed as the gold standard in the identification of drug-drug interaction. Main outcome Sensitivity, specificity, positive and negative predictive values. Results The programs studied were: Drug Interaction Checker (DIC), Drug-Reax (DR), and Lexi-Interact (LI). DR displayed the highest sensitivity (0.88) and DIC showed the lowest (0.69). A close similarity was observed among the programs regarding specificity (0.88-0.92) and positive predictive values (0.88-0.89). The DIC had the lowest negative predictive value (0.75) and DR the highest (0.91). Conclusion The DR and LI programs displayed appropriate sensitivity and specificity for identifying drug-drug interactions of interest in intensive care units. Drug interaction software programs help pharmacists and health care teams in the prevention and recognition of drug-drug interactions and optimize safety and quality of care delivered in intensive care units.

Care during the intensive phase: promotion of adherence

The standards in this chapter focus on maximising the patient`s ability to adhere to the treatment prescribed. Many people are extremely shocked when they are told they have TB, some refuse to accept it and others are relieved to find out what is wrong and that treatment is available. The reaction depends on many factors, including cultural beliefs and values, previous experience and knowledge of the disease. Even though TB is more common among vulnerable groups, it can affect anyone and it is important for patients to be able to discuss their concerns in relation to their own individual context. The cure for TB relies on the patient receiving a full, uninterrupted course of treatment, which can only be achieved if the patient and the health service work together. A system needs to be in place to trace patients who miss their appointments for treatment (late patients). The best success will be achieved through the use of flexible, innovative and individualised approaches. The treatment and care the patient has received will inevitably have an impact on his or her willingness to attend in the future. A well-defined system of late patient tracing is mandatory in all situations. However, when the rates are high (above 10%), any tracing system will be useless without also examining the service as a whole.

City tuberculosis control coordinators` perspectives of patient adherence to DOT in Sao Paulo State, Brazil, 2005

SETTING: Thirty-six priority cities in Sao Paulo State, Brazil, with a high incidence of tuberculosis (TB) cases, deaths and treatment default. OBJECTIVE: To identify the perspectives of city TB control coordinators regarding the most important components of adherence strategies adopted by health care teams to ensure patient adherence in 36 priority cities in the State of Sao Paulo, Brazil. DESIGN: Qualitative research with semi-structured interviews conducted with the coordinators of the National TB Control Programme involved in the management of TB treatment services in the public sector. RESULTS: The main issues thought to influence adherence to directly observed treatment (DOT) by coordinators include incentives and benefits delivered to patients, patient-health care worker bonding and comprehensive care, the encouragement given by others to follow treatment (family, neighbours and health professionals), and help provided by health professionals for patients to recover their self-esteem. CONCLUSION: The main aspects mentioned by city TB control coordinators regarding patient adherence to treatment and to DOT in Sao Paulo are improvements in communications, relationships based on trust, a humane approach and including the patients in the decision-making process concerning their health.

Antimicrobial drug administration errors identified in Brazilian multicentric study

Medication administration errors (MAE) are the most frequent kind of medication errors. Errors with antimicrobial drugs (AD) are relevant because they may interfere inpatient safety and in the development of microbial resistance. The aim of this study is to analyze the AD errors detected in a Brazilian multicentric study of MAE. It was a devcriptive and explorotory study carried out in clinical units in five Brazilian teaching hospitals. The hospitals were investigated during 30 days. MAE were detected by observation technique. MAE were classified in categories: wrong route(WR), wrong patient(WP), wrong dose(WD) wrong time (WT) and unordered drug (UD). AD with MA E were classified by Anatomical-Therapeutical-Chemical Classification System. AD with narrow therapeutic index (NTI) wet-e identified A descriptive statistical analysis was performed using SPSS version 11.5 software. A total of 1500 errors were observed, 277 (18.5%) of them were error with AD. The hopes of AD error were: WT87.7%, QD 6.9%, WR 1.5%, UD 3.2% and WP 0.7%. The number of AD found was 36. The mostly ATC class were fluoroquinolones 13.9%, combinations of penicillin 13.9%, macrolides 8.3% and third-generation cephalosporines 5.6%. The parenteral drug dosage form was associated with 55.6% of AD. 16.7% of AD were NTI. 47.4% of WD and 21.8% WT were with NTI drugs. This study shows that these errors should be considered potential areas for improvement in the medication process and patient safety plus there is requirement to develop rational drug use of AD.

Intrinsic Dissolution as a Tool for Evaluating Drug Solubility in Accordance with the Biopharmaceutics Classification System

The Biopharmaceutics Classification System (BCS) is a tool that was created to categorize drugs into different groups according to their solubility and permeability characteristics. Through a combination of these factors and physiological parameters, it is possible to understand the absorption behavior of a drug in the gastrointestinal tract, thus contributing to cost and time reductions in drug development, as well as reducing exposure of human subjects during in vivo trials. Solubility is attained by determining the equilibrium under conditions of physiological pH, while different methods may be employed for evaluating permeability. On the other hand, the intrinsic dissolution rate (IDR), which is defined as the rate of dissolution of a pure substance under constant temperature, pH, and surface area conditions, among others, may present greater correlation to the in vivo dissolution dynamic than the solubility test. The purpose of this work is to discuss the intrinsic dissolution test as a tool for determining the solubility of drugs within the scope of the Biopharmaceutics Classification System (BCS).

Obtention and Evaluation of Inclusion Complexes of Furosemide with beta-ciclodextrin and hidroxipropil-beta-ciclodextrin: Effects on Drug`s Dissolution Properties

Obtention and Evaluation of Inclusion Complexes of Furosemide with beta-ciclodextrin and hidroxipropil-beta-ciclodextrin: Effects on Drug`s Dissolution Properties. The purpose of this study was to prepare, characterize and evaluate the dissolution behavior of inclusion complexes of furosemide with beta-cyclodextrin (beta-CD) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD). Solid complexes of furosemide with P-CD and-HP-beta-CD were prepared by using a freeze-drying method. Physical mixtures were prepared for comparison. The inclusion complexes were characterized by differential scanning calorimetry (DSC), Infrared (IR) and dissolution test. ""In vitro"" dissolutions assays were performed at pH 1,2; pH 4,5 and pH 6,8 media for a 60 min period. Statistical analysis employing ANOVA and Tukey`s Test, for the dissolution efficiency values (ED%), showed that complexation of furosemide with both cyclodextrins improved significantly ED% of the drug in all tested media, suggesting a minor pH influence on dissolution properties of the drug.

Micromethod for Quantification of Carbamazepine, Phenobartital and Phenytoin in Human Plasma by HPLC-UV Detection for Therapeutic Drug Monitoring Application

A simple, rapid, selective and sensitive analytical method by HPLC with UV detection was developed for the quantification of carbamazepine, phenobarbital and phenytoin in only 0.2 mL of plasma. A C18 column (150 x 3.9 mm, 4 micra) using a binary mobile phase consisting of water and acetonitrile (70:30, v/v) at a flow rate of 0.5 mL/min were proposed. Validation of the analytical method showed a good linearity (0.3 to 20.0 mg/L for CBZ, 0.9 to 60.0 mg/L for PB and 0.6 to 40.0 mg/L for PHT), high sensitivity (LOQ: 0.3, 0.9 and 0.6 mg/L respectively). The method was applied for drug monitoring of antiepileptic drugs (AED) in 27 patients with epilepsy under polytherapy.

Ruthenium-nitrite complex as pro-drug releases NO in a tissue and enzyme-dependent way

Nitric oxide (NO) plays an important role in the control of the vascular tone and the most often employed NO donors have limitations due to their harmful side-effects. In this context, new NO donors have been prepared, in order to minimize such undesirable effects. cis-[Ru(bpy)(2)(py)NO(2)](PF(6)) (RuBPY) is a new nitrite complex synthesized in our laboratory that releases NO in the presence of the vascular tissue only. In this work the vasorelaxation induced by this NO donor has been studied and compared to that obtained with the well known NO donor SNP. The relaxation induced by RuBPY is concentration-dependent in denuded rat aortas pre-contracted with phenylephrine (EC(50)). This new compound induced relaxation with efficacy similar to that of SNP, although its potency is lower. The time elapsed until maximum relaxation is achieved (E(max) = 240 s) is similar to measured for SNP (210 s). Vascular reactivity experiments demonstrated that aortic relaxation by RuBPY is inhibited by the soluble guanylyl-cyclase inhibitor 1H-[1,2,4] oxadiozolo[4,3-a]quinoxaline-1-one (ODQ 1 mu M). In a similar way, 1 mu M ODQ also reduces NO release from the complex as measured with DAF-2 DA by confocal microscopy. These findings suggest that this new complex RuBPY that has nitrite in its structure releases NO inside the vascular smooth muscle cell. This ruthenium complex releases significant amounts of NO only in the presence of the aortic tissue. Reduction of nitrite to NO is most probably dependent on the soluble guanylyl-cyclase enzyme, since NO release is inhibited by ODQ. (C) 2011 Elsevier Inc. All rights reserved.

In situ gelling hexagonal phases for sustained release of an anti-addiction drug

In this study, fluid precursor formulations for subcutaneous injection and in situ formation of hexagonal phase gels upon water absorption were developed as a strategy to sustain the release of naltrexone, a drug used for treatment of drug addiction. Precursor formulations were obtained by combining BRIJ 97 with propylene glycol (PG, 5-70%, w/w). To study the phase behavior of these formulations, water was added at 10-90% (w/w), and the resulting systems were characterized by polarized light microscopy. Two precursor formulations containing BRIJ:PG at 95:5 (w/w, referred to as BRIJ-95) and at 80:20 (w/w, referred to as BRIJ-80) were chosen. Naltrexone was dissolved at 1% or suspended at 5% (w/w). Precursor formulations were transformed into hexagonal phases when water content exceeded 20%. Water uptake followed second-order kinetics, and after 2-4 h all precursor formulations were transformed into hexagonal phases. Drug release was prolonged by the precursor formulations (compared to a drug solution in PBS), and followed pseudo-first order kinetics regardless of naltrexone concentration. The release from BRIJ-80 was significantly higher than that from BRIJ-95 after 48 h. The relative safety of the precursor formulations was assessed in cultured fibroblasts. Even though BRIJ-95 was more cytotoxic than BRIJ-80, both precursor formulations were significantly less cytotoxic than sodium lauryl sulfate (considered moderate-to-severe irritant) at the same concentration (up to 50 mu g/mL). These results suggest the potential of BRIJ-based precursor formulations for sustained naltrexone release. (C) 2011 Elsevier By. All rights reserved.

Using Computer-aided Drug Design and Medicinal Chemistry Strategies in the Fight Against Diabetes

The aim of this work is to present a simple, practical and efficient protocol for drug design, in particular Diabetes, which includes selection of the illness, good choice of a target as well as a bioactive ligand and then usage of various computer aided drug design and medicinal chemistry tools to design novel potential drug candidates in different diseases. We have selected the validated target dipeptidyl peptidase IV (DPP-IV), whose inhibition contributes to reduce glucose levels in type 2 diabetes patients. The most active inhibitor with complex X-ray structure reported was initially extracted from the BindingDB database. By using molecular modification strategies widely used in medicinal chemistry, besides current state-of-the-art tools in drug design (including flexible docking, virtual screening, molecular interaction fields, molecular dynamics. ADME and toxicity predictions), we have proposed 4 novel potential DPP-IV inhibitors with drug properties for Diabetes control, which have been supported and validated by all the computational tools used herewith.

The Pharmaceutical care of patients with type 2 diabetes mellitus

Objective To evaluate the efficiency of pharmaceutical care on the control of clinical parameters, such as fasting glycaemia and glycosylated haemoglobin in patients with Type 2 Diabetes mellitus. Setting This study was conducted at the Training and Community Health Centre of the College of Medicine of Ribeirao Preto, University of Sao Paulo, Brazil. Methods A prospective and experimental study was conducted with 71 participants divided in two groups: (i) pharmaceutical care group (n=40), and (ii) the control group (n=31). The distribution of patients within these groups was made casually, and the patients were monitored for 12 months. Main outcome measure: Values for fasting glycaemia and glycosylated haemoglobin were collected. Results Mean values of fasting glycaemia in the pharmaceutical care group were significantly reduced whilst a small reduction was detected in the control group at the same time. A significant reduction in the levels of glycosylated haemoglobin was detected in patients in the pharmaceutical care group, and an average increase was observed in the control group. Furthermore, the follow-up of the intervention group by a pharmacist contributed to the resolution of 62.7% of 142 drug therapy problems identified. Conclusion In Brazil, the information provided by a pharmacist to patients with Type 2 Diabetes mellitus increases compliance to treatment, solving or reducing the Drug Therapy Problem and, consequently, improving glycaemic control.

Iontophoretic transport of zinc phthalocyanine tetrasulfonic acid as a tool to improve drug topical delivery

Phthalocyanines have been used as systemic photosensitizers because of their high affinity towards tumour tissue, and the high rates of reactive oxygen species produced when they are irradiated during photodynamic therapy. However, the topical administration of these compounds is limited by their large size, poor hydrosolubility and ionic character. This study aimed to investigate the iontophoretic delivery of charged zinc phthalocyanine tetrasulfonic acid (ZnPcS(4)) from a hydrophilic gel to different skin layers by means of in-vitro and in-vivo studies. Six hours of passive administration was insufficient for ZnPcS(4) to cross the stratum corneum (SC) and to reach the epidermis and dermis. No positive effect was reached when anodal iontophoresis was performed, showing that the drug-electrode attraction effect was higher than the electro-osmosis contribution at a pH of 5.5. Cathodal iontophoresis, however, was able to transport significant amounts of the drug to the viable epidermis. In addition, the absence of NaCl in the formulation significantly increased (by five-fold) the amount of ZnPcS(4) that crossed the SC and accumulated in the epidermis and dermis. It was possible to visualize the drug accumulation in the follicle openings and in the epidermis, even after SC removal. In-vivo experiments in rat skin showed that these results were maintained in an in-vivo model, even with only 15 min of iontophoresis. In addition, confocal analysis of the treated skin showed a homogeneous distribution of ZnPcS(4) in the viable epidermis after this short period of cathodal iontophoresis. Anti-Cancer Drugs 22:783-793 (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.