Avaliação da qualidade da água purificada em farmácias magistrais da região de São José do Rio Preto, SP / Quality assessment of purified water used in pharmacies in São José do Rio Preto, SP

A água é a matéria-prima mais utilizada na produção de várias formas farmacêuticas, sendo um constituinte da própria formulação e exigindo para tal uma série de especificações físico-químicas e microbiológicas. Além disso, é um insumo de utilização imprescindível para testes laboratoriais e procedimentos de limpeza de equipamentos e utensílios. O presente trabalho teve como objetivo verificar o grau de contaminação química e microbiana em água purificada utilizada em farmácias magistrais da região de São José do Rio Preto, SP. As coletas foram realizadas segundo recomendações da USP Pharmacopeia, com os devidos cuidados de assepsia, e as amostras encaminhadas imediatamente ao laboratório de controle de qualidade. Foram analisados vários parâmetros físico-químicos, tais como aspecto, pH, condutividade, resíduo por evaporação, amônia, cálcio, cloreto, metais pesados, sulfato e substâncias oxidáveis, além de parâmetros microbiológicos, como contagem total de aeróbios e pesquisa de coliformes totais e termotolerantes e Pseudomonas aeruginosa. Os resultados indicaram alguns parâmetros de não conformidade: em 10% das amostras analisadas para o pH e pesquisa de impurezas inorgânicas, em 17% para condutividade, em 14% para substâncias oxidáveis e em 20% para análise microbiológica, ressaltando a necessidade de maior rigor na produção e qualidade da água purificada produzida e/ou armazenada nesses estabelecimentos farmacêuticos.

Water is the raw material used most in the production of diverse pharmaceutical forms and, being a constituent of the formulation itself, is subject to a number of physico-chemical and microbiological specifications. In addition, it is indispensable for laboratory tests and the cleaning of equipment and apparatus. The aim of this study was to ascertain the degree of physicochemical and microbiological contamination of purified water used in compounding pharmacies in the city of São José do Rio Preto, SP, Brazil. Samples were taken as recommended in the USP Pharmacopeia, with careful aseptic technique, and sent immediately the to quality control laboratory. Physicochemical properties were analyzed, including appearance, pH, conductivity, residue after evaporation, ammonia, calcium, chloride, heavy metals, sulfate and oxidizable substances, and microbiological tests were performed: total aerobic microbial count and detection of total and thermotolerant coliforms and Pseudomonas aeruginosa. Results showed that some parameters did not conform to the standards, especially pH, conductivity, inorganic impurities, oxidizable substances and microbiological test data, in 10%, 17%, 10%, 14% and 20% of the analyzed samples, respectively, This points to the need for greater care in the production and/or storage of purified water in these pharmaceutical establishments.

Desenvolvimento de metodologia qualitativa para identificação de ceftazidima / Qualitative methods for the identification of ceftazidime

A partir deste estudo, métodos para análise qualitativa foram desenvolvidos a fim de identificar ceftazidima em matéria-prima e em formulações farmacêuticas. Esses métodos incluíram testes físico-químicos baseados em propriedades químicas por reações clássicas de coloração e testes instrumentais, tais como cromatografia em camada delgada, calorimetria e espectroscopia no ultravioleta. Os resultados foram obtidos diretamente através de identificação visual pela coloração desenvolvida e pela análise dos espectros obtidos nos testes instrumentais. Esses métodos mostraram-se reprodutíveis e rápidos para identificar ceftazidima na presença de outros antibióticos ?-lactâmicos, podendo ser usados rotineiramente em análises de controle de qualidade

In this study, qualitative analytical methods were developed for the identification of ceftazidime in raw material and in pharmaceutical formulations. These methods included physicochemical tests based on chemical properties, performed by classical colorimetric reactions, and instrumental tests, such as thin-layer chromatography, calorimetry and ultraviolet spectroscopy. Results were obtained directly, through the visual identification of the drug by the color developed, and by analyzing the spectra obtained. These methods proved to be reproducible and fast means of identifying ceftazidime in the presence of other beta-lactam antibiotics and may be used for routine quality control tests.

Left ventricular performance in endotoxin shock in dogs.

Endotoxin shock, with maximal velocity of contraction (Vmax) as our index of contractility, showed no myocardial depression in an earlier 4-h study (Guntheroth, Proc. Soc. Exp. Biol. Med. 157: 610--614, 1978). Because of reports of late deterioration, we studied six dogs until spontaneous death (9--18 h). Heart rate nearly doubled and left ventricular filling pressure and aortic mean pressure fell, but Vmax did not change significantly. Because of concern that the marked increase in heart rate may have contributed to an artifactual maintenance of Vmax (due to its frequency dependence, inherent in dp/dt), we studied a final group of five dogs with three additional indicators of contractility. End-systolic pressure-diameter ratio (Emax), ejection fraction (sonar-determined from the minor axis of the left ventricle), and frequency-normalized average rate of generation of power density (FARPD) all fell early and remained low until death. We conclude that myocardial contractility is significantly reduced in endotoxin shock, early and sustained. Its presence is masked somewhat in the untreated subject by the reduced work load, secondary to hypovolemia.

Irreversible thermodynamics of an isometric twitch, time-dependent general formulation.

We used the phenomenological laws of irreversible thermodynamics, to derive a system of coupled differential equations describing the time course of the mechanochemical coupling underlying an isometric twitch. Our general description is concerned only with the fundamental process of energy transduction taking place within an idealized unit element of muscle and does not include the description of associated processes such as the excitation-contraction coupling and the mechanical or external coupling that, in bulk muscle, lead to or mediate the fundamental process. The values of the initial conditions and of four parameters are required to solve for the time course of the process. Two of the parameters have a clear physical interpretation and, for the specific case of muscular contraction involving hydrolysis of ATP, their values can be readily estimated from available experimental data. The interpretation of the two other parameters is more speculative, but, from their strong interdependence with the other parameters, their values can be also approximated. Solution of the coupled differential equations yields results consistent with the typical experimental time course of an isometric twitch.

Rate of generation of myocardial power density normalized by cardiac frequency.

We introduce a frequency normalized, power averaged, rate of generation of power density (FARPD) that extends the range of applicability of the averaged rate of generation of power density (ARPD) to any cardiac frequency encountered in experimental or clinical situations. Normalization eliminates the frequency-dependent mathematical artifacts arising during the computation of quantities containing time derivatives of the pressure, while preserving the effects of changes in heart rate on the cardiac muscle itself (Bowditch type of phenomena). The distribution of normal values in a group of 51 control dogs was very close to the standard normal distribution. These values had no statistically significant differences with those of a smaller control group studied by independent investigators. Isoproterenol and propranolol produced highly significant statistical changes in FARPD. Alterations in pre- and afterload produced changes that were not significant for the former and significant at the 5% level for the latter. These changes were small when compared to those resulting from typical inotropic interventions.

Constant-pressure coronary artery perfusion during aortic valve operations.

We considered the theoretical differences between the normal relationships of coronary blood flow and perfusion pressure in the working heart and those obtained with continuous, steady-flow perfusion by a roller pump during aortic valve replacement. Steady pump perfusion should deliver less blood flow to the endocardium because: 1. For the same mean artery perfusion pressure, the average coronary blood flow is less with constant-flow pump perfusion. 2. With constant pump perfusion, pressure would be excessively high during systole, and during diastole it would be significantly lower than the mean perfusion pressure. Instantaneous pressure and flow were measured in the left coronary artery in 8 patients undergoing aortic valve replacement, employing either roller pump perfusion or a gravity flow system to provide a steady pressure source. Although we did not attempt to demonstrate improved endocardial flow, the mean left coronary flow was always greater with gravity perfusion (297 versus 153 ml/min), lending support to the theoretically proposed differences between the two perfusion methods.

Myocardial contractile reserve and indices of contractility.

A close examiniation of several indices of contractility derived from the ventricular pressure was made using an isolated canine heart preparation. The repsonses to single intracoronary injections of calcium chloride as well as to increasing doses of this agent were tested. From the latter, calcium dose-transient-response curves intended to reveal the extent of myocardial/contractile reserve were constructed. Indices included various extrapolations to maximal velocity of shortening at zero load, maximal value of the quotient of the first derivative and ventricular pressure, time-tension index, energy averaged power density, and power averaged rate of generation of power density. Indices were compared over the same cardiac cycles before and after administration of calcium. Most indices showed increments from 10 to 20%, except power density functions which had increments of 40 and 70%, respectively. Calcium dose-response curves were linear for most indices, but, again, the power density functions showed the steepest slopes. After severe coronary occlusion, the curves for most indices flattened and lost linearity and, presumably, this was due to loss of myocardial contractile reserve. For milder occlusions, only the power density functions showed significant flattening. The conceptual framework of a contractile myocardial reserve appears supported by these results.

Hepatic artery flow improvement after portacaval shunt: a single hemodynamic clinical correlate.

We have documented a highly significant increment in hepatic arterial flow following a portacaval shunt in patients with cirrhosis of the liver and portal hypertension. In contrast with other hemodynamic variables, the increment in arterial flow was directly related to morbidity, hospital mortality, and long term survival. Patients with increments smaller than 100 ml/min had the worst clinical results. They accounted for all of the hospital mortality, the largest incidence of encephalopathy, and the worst long term cumulative survival rates. The extent of the increment was not related directly to the type of shunt but, rather, to some intrinsic capability of the cirrhotic liver to increase its arterial flow in response to the relief of sinusoidal hypertension produced by the shunt. This capablilty appears related to the degree of entrapment of the hepatic arterioles by the fibrous tissues of cirrhosis. This encasement of arterioles should change the elastic properties of the hepatic arterial bed and we propose to measure these properties by determining the characteristic input impedance of the arterial bed.

Spontaneous reversal of portal blood flow: the case for and against its occurrence in patients with cirrhosis of the liver.

Because of its presumed serious clinical significance, we made an analysis of the evidence for and against the occurrence of spontaneous reversal of portal flow in cirrhosis of the liver. We examined the evidence obtained from manometric studies, radioactive tracer studies, radiologic studies, and actual measurements of magnitude and direction of portal blood flow. Concerning manometric studies, we introduced a physical analysis, based on first principles, which demonstrates that the occluded portal pressures cannot be used to construct a hydraulic gradient for portal flow. Similarly, we examined the weakness of the evidence derived from radioactive tracer and radiologic studies and, in the latter, the drastically opposite results reported by different investigators. Finally, we found that actual measurements of magnitude and direction of portal flow provide impressive evidence against the occurrence of spontaneous reversal of portal flow in cirrhosis. We conclude that unless new and convincing evidence is provided, it may not serve the best interests of medicine and of our patients to continue accepting spontaneous reversal of portal flow in cirrhosis as if it were a proven phenomenon.

The hemodynamics of portal hypertension revisited: determinants and significance of occluded portal pressures.

We bring up to date our series of direct measurements of portal flow and pressure in patients with cirrhosis of the liver. In 153 patients the portal flow averaged 447 plus or minus 350 ml. Hg per minute and the portal pressure 28.5 plus or minus 4 mm. Hg (approximately 387 mm. H2O). Both quantities compare favorably with our previous measurements in smaller groups of patients. In 80 of our patients we had also measurements of pressure on the hepatic and splanchnic sides of a clamp occluding the portal vein. Nine of these patients had an hepatic occluded portal pressure higher than either or both the free portal pressure and the splanchnic occluded portal pressure. Of these nine patients with reversed pressure differences, two had stagnant portal flow and the remaining seven had forward flow into the liver measuring from 80 to 1,116 ml. Hg per minute.