Use Of Drug Therapy Research Articles

Innovative first order elimination kinetics working model for easy learning

Background: General pharmacology is the backbone of therapeutic pharmacology. In general pharmacology, pharmacokinetics is a very difficult topic for undergraduate medical students. Knowledge of the kinetics and of the effects of drugs is necessary for the correct use of drugs in therapy. As in the body most of the drugs follow first order elimination kinetics, so it is necessary for all students to know about basic concept of first order kinetics. This can be easily understood by using working models. Our present study is a step in that direction. The objective of this study was planned to develop first order elimination kinetics working models to teach pharmacokinetics principle to the under graduate medical students.Methods: The current study was planned and executed by the department of pharmacology in SHKM government medical college, Mewat, Haryana, India in the first quarter of 2016. This model was developed from household waste materials like thermocol sheets, coke bottles, waste water pipe, colour etc.Results: As we know learning is better with live experimentation as compare to theoretical learning, so difficult topics such as elimination kinetics will be taught by help of working models.Conclusions: First order elimination kinetics is easily understood with the help of above working model. More and more working models could be developed for teaching difficult topics.

Changes in vascular reactivity caused by angiotensin II in heart resistance vessels and isolated vessels of rat aorta in a model of hypertension (1088.1)

Hypertension is a disease with high morbidity and mortality and is considered one of the main etiological factors of multiple pathologies. One of the regulatory mechanisms of blood pressure is the Renin Angiotensin System (RAS), so much so that the first‐line drugs in the treatment of hypertension are directed to some of the components of the RAS. One therapy that has been shown clinically to improve the condition of patients with hypertension is hyperbaric oxygenation (HBO). HBO has been shown to improve vascular smooth muscle relaxation. The aim of this study is analyze the effect of HBO on the RAS. Methods: hypertension was induced in male Wistar rats. Hypertensive rats received HBO and at the end of the treatment were sacrificed getting heart, thoracic and abdominal aorta; and then they were placed in an isolated organ system where we made concentration response curves to Ang II. Conclusion:HBO therapy reduces the reactivity in coronary resistance arteries under Ang II stimulation and reduced vascular reactivity in both segments of the hypertensive rat aorta. This suggests that HBO could possibly be used with hypertensive patients to reduce the use of drugs in therapy.Grant Funding Source: COFAA / IPN

Inhibitory effect of mycophenolic acid on the replication of infectious pancreatic necrosis virus and viral hemorrhagic septicemia virus

Infectious pancreatic necrosis virus (IPNV) and viral hemorrhagic septicemia virus (VHSV) remain two of the most important pathogens of farmed trout worldwide. Mycophenolic acid (MPA) is an inhibitor of cellular inosine monophosphate dehydrogenase (IMPDH), an enzyme that catalyzes an essential step in the biosynthesis of GTP. In this report, the antiviral activity of MPA against IPNV and VHSV in cell culture was assessed. Cell viability, virus yield, protein and RNA synthesis determinations were used to evaluate the inhibitory effect of MPA. MPA caused a dose-dependent inhibition of IPNV and VHSV replication. It was found that MPA had a particularly potent effect against IPNV, inhibiting the production of infectious virus more than 10 5-fold. MPA was also highly effective in preventing viral protein synthesis. Quantitative real-time RT-PCR was used to measure viral RNA in cells infected by IPNV or VHSV to evaluate the inhibitory capacity of MPA as well as to compare MPA to the established antiviral drug ribavirin. MPA showed a good efficacy in decreasing accumulation of viral RNA at low concentrations. Finally, time of addition and wash out experiments suggested that MPA may have a dual mechanism of action, targeting both a cell and a viral function. This study provides evidence that MPA can function as a broad-spectrum antiviral drug for use in therapy of rainbow trout diseases.

Epoetin Alfa Drug Use Evaluation Using A Software System

Objective: To assess the utility of using a computer software program to determine whether epoetin alfa therapy drug use evaluation (DUE) criteria were met. Study design: Computer software was designed to allow pharmacists to enter patient data such as haematocrit results and iron stores into a database. DUE data were collected upon entry into the study (through medical record review), at 6 months and at 12 months after enrollment for both the treatment and control groups (see Interventions section). The analyses of the 6- and 12-month DUE process and outcome criteria were conducted through an automated algorithm that was part of the software. The DUE evaluation was collected as part of a randomised, prospective, controlled study conducted at 32 sites across the US. Interventions: At least 1 pharmacist at each study site completed a 4-day training session on end-stage renal disease and haemodialysis treatment, principles of anaemia management, use of an epoetin alfa software program, and review of specific DUE criteria. The treatment group consisted of patients managed by a trained pharmacist working in collaboration with a nephrologist being responsible for monitoring, evaluating and recommending epoetin alfa dosage regimens for patients. The control group consisted of patients for whom pharmacists monitored and collected haematocrit data but did not recommend therapy to the nephrologists. Main outcome measures and results: There were no statistically significant differences between patients in both the treatment and control groups with regard to the DUE results. However, the study demonstrated that computer databases can assist in determining whether specific DUE criteria have been met at multiple patient care sites. The computer software applied the same consistent methodology across a broad range of hospital practice sites and thus may have minimised investigator bias or site to site variations in criteria application. Conclusions: Future DUE software algorithms should allow investigators/pharmacists to adjust important parameters such as the criterion threshold, time period of monitoring, ability to code ‘excused’ gaps in data and flexibility to modify criterion parameters.

Analysis of protein glycosylation by mass spectrometry.

There is a growing pharmaceutical market for protein-based drugs for use in therapy and diagnosis. The rapid developments in molecular and cell biology have resulted in production of expression systems for manufacturing of recombinant proteins and monoclonal antibodies. These proteins are glycosylated when expressed in cell systems with glycosylation ability. For glycoproteins intended for therapeutic administration it is important to have knowledge about the structure of the carbohydrate side chains to avoid cell systems that produce structures, which in humans can cause undesired reactions, e.g., immunological and unfavorable serum clearance rate. Structural analysis of glycoprotein oligosaccharides requires sophisticated instruments like mass spectrometers and nuclear magnetic resonance spectrometers. However, before the structural analysis can be conducted, the carbohydrate chains have to be released from the protein and purified to homogeneity, and this is often the most time-consuming step. Mass spectrometry has played and still plays an important role in analysis of protein glycosylation. The superior sensitivity compared to other spectroscopic methods is its main asset. Structural analysis of carbohydrates faces several problems, however, due to the chemical nature of the constituent monosaccharide residues. For oligosaccharides or glycoconjugates, the structural information from mass spectrometry is essentially limited to monosaccharide sequence, molecular weight, an only in exceptional cases glycosidic linkage positions can be obtained. In order to completely establish an oligosaccharide structure, several other structural parameters have to be determined, e.g., linkage positions, anomeric configuration and identification of the monosaccharide building blocks. One way to address some of these problems is to work on chemical pretreatment of the glycoconjugate, to specifically modify the carbohydrate chain. In order to introduce specific modifications, we have used periodate oxidation and trifluoroacetolysis with the objective of determining glycosidic linkage positions by mass spectrometry.

Pharmacokinetics of calcium-entry blockers

Effective use of drugs in therapy depends not only on clinical acumen but also on the availability of relevant pharmacokinetic and pharmacodynamic data. Such information assists in development of safe dosing regimens, prediction of abnormal handling of drugs in states of disease and disorder and anticipation of drug interactions. For the calciumentry blocking agents now available in the United States (verapamil, nifedipine and diltiazem), these data appeared well after clinical patterns of use evolved. Nonetheless, their relevance continues to be demonstrated by the dependence of each agent on intact liver blood flow and function for normal rates of elimination; by the nonlinear kinetic characteristics for verapamil and diltiazem (and probably for nifedipine, as well) and the derivative implications for decreased dosing frequency requirements; and by observations now appearing on the relation between plasma drug levels and drug effects, both therapeutic and toxic. Such data are discussed herein, with emphasis on those aspects that impact on the clinical use of the calcium-entry antagonists.