No abstract

Studies on oral kinetics (Blood and tissues) after single therapeutic dose of cefpirome (20mg/kg oral) in rats of either sex and on some biochemical parameters, tissue residue, and spermatozoa motility in male rats after cefpirome administration (20mg/kg oral bid 7days) were undertaken so that generated data could be extrapolated to humans. For kinetic studies, 24 Wister rats of either sex, 3 months of age, (180-210gm) were used (Groups I-IV; n=6). Blood samples collected from each animal of Group I-IV at 0 h to serve as predrug control. All the groups (I-IV) received cefpirome 20mg/kg once orally as a single dose. At the end of 1, 4, 12, and 24 hour post oral administration, Groups I, II, III, and IV were utilized for kinetic studies. Blood samples were collected from each animal and vital organs namely brain, lung, liver, spleen, kidney, and heart, were studied for drug analysis and determination of weight. For biochemical parameters, tissue residue and spermatozoa motility, 12male rats were randomly divided into Groups A and B (n=6). Group B received cefpirome (20mg/kg orally bid 7 days) while Group A served as control. Biochemical parameters [Blood glucose, protein, Aspartate transaminase (AST), Alanine transaminase (ALT), and hemoglobin] were measured at 0 and 7 th day while sperm count (Total, live and dead) and mean organ weight (Study and control group) and tissue residue of drug were evaluated at the end of treatment. Absorption of cefpirome was observed at 2h and reached a maximum at 4h and persisted in blood till 24h. Elimination half-life in lung was highest followed by heart, liver, kidney, and spleen while t½, k in plasma was very low suggesting more affinity of cefpirome for tissues than blood. Blood glucose, protein, AST, and ALT activities were not significantly altered but the hemoglobin level and total and live sperm count decreased significantly in the study group compared to the control group. Residual level of cefpirome was highest in liver followed by kidney and other study organs. Therefore, the drug should be used in human beings judiciously.

Angiotensin II receptor blockers (ARBs) are the newest class of approved antihypertensive agents and the second class of drugs to exert their primary antihypertensive action by interrupting the renin-angiotensin system. It was a multicenter, randomized, double-blind trial in which efficacy of Olmesartan (20mg once a day) and losartan (50mg once a day) was compared in patients with hypertension. In patients with a cuff diastolic blood pressure (DBP) of ≥100 and ≥115 mm Hg and a mean daytime DBP of ≥90mm Hg and <120mm Hg, as measured by ambulatory blood pressure monitoring. Cuff and ambulatory blood pressures were monitored at baseline and after 8 weeks of treatment. All groups were adults and approximately 62% male, and their mean age was approximately 52 years. In all groups, mean baseline DBP and systolic blood pressure (SBP) were approximately 104 and 157mm Hg, respectively. The reduction of sitting cuff DBP with olmesartan (13.5mm Hg), the primary efficacy variable of this study, was significantly greater than with losartan, enalapril, and quinapril (8.2, 7.9, and 9.9mm Hg, respectively). Reductions of cuff SBP with the four ARBs ranged from 8.4-13.3mm Hg and were not significantly different. The reduction in mean 24-hour DBP with olmesartan (8.5mm Hg) was significantly greater than reductions with losartan and enalapril (6.2 and 5.6mm Hg, respectively) and showed a trend toward significance when compared to the reduction in DBP with quinapril (7.4mm Hg; p=0.087). The reduction in mean 24-hour SBP with olmesartan (12.5mm Hg) was significantly greater than the reductions with losartan and enalapril (9.0 and 8.1mm Hg, respectively) and equivalent to the reduction with quinapril (11.3mm Hg). All drugs were well tolerated. The authors conclude that olmesartan, at its starting dose, is more effective than the starting doses of the other tested drugs in reducing cuff DBP in patients with essential hypertension. KEYWORDS: Essential Hypertension, Enalapril, Losartan, Olmesartan. INTRODUCTION:Angiotensin II receptor blockers (ARBs) are the newest class of approved antihypertensive agents and the second class of drugs to exert their primary antihypertensive action by interrupting the renin-angiotensin system. ARBs prevent the hypertensive effects of angiotensin II by selective blockade of the angiotensin II type 1 (AT1) receptor. Olmesartan is a new ARB that was discovered during a systematic survey of the AT1 binding actions of substituted imidazole-5-carboxylic acids.It is a prodrug that, following oral administration, is rapidly and completely de-esterified in the gut to its active form, in a reaction that is not cytochrome P-450-dependent. This active metabolite, olmesartan, is a potent and selective AT1 receptor antagonist, with no agonist activity. 1,2,3 In healthy subjects, olmesartan has an elimination half-life of 12-18 hours, a value that is comparable to the longest half-lives of ARBs currently in clinical use.

Background: There is increased concern regarding the inappropriate use of antimicrobials resulting in emergence of resistant strains, unnecessary adverse effects and poor therapeutic outcome. This present study has been taken up with a view to analyze the use of various antimicrobial agents alone and/or in combination to combat diseases of infective origin in a proposed manner.Methods: This was a prospective study carried out for a period of 1 year from January 2011 to December 2011. The prescriptions of all eligible patients were reviewed on daily basis and all the relevant data were retrieved to assess the utilization pattern of antimicrobials and also their safety and potential interactions.Results: A total of 500 patients were selected randomly who satisfied the inclusion criteria. Of the total selected patients with infectious diseases, 493 patients (98.6%) received one or more antimicrobials. Use of antimicrobials was high in the age group of ‘6 months to 3 years’, ‘rural patients’ constituted 62% and were mostly from ‘Lower Socio-economic status’ (46%). Respiratory diseases constituted 38% of the patients. Fever was the notable symptom in 68.4%. Cephalosporins (48.6%) were the most frequently prescribed class of antimicrobials. Combination of ‘Parenteral therapy followed by oral therapy’ was the preferred route in 92%, and a combination of two antimicrobials was seen in 34.4%. Majority of the patients (81%) were discharged on advice and most of the patients (37.6%) had duration of stay of 7-9 days. 25.8% reported ‘Adverse Drug Reactions’ including predictable and unpredictable reactions.Conclusions: Antimicrobial prescribing is common in pediatric infectious diseases. As inappropriate usage of systemic antimicrobials was observed, it is essential that appropriate guidelines on the use of systemic antimicrobials are implanted to ensure rational prescribing of antimicrobials.

Diabetes mellitus is associated with increased oxidative stress due to hyperglycemia. This increased oxidative stress gives rise to micro and macro vascular complications. MATERIALS & METHODS: Randomized comparative prospective trial. Three groups were formed comprising of metformin + losartan, Metformin + Glimepiride + Losartan and metformin + Repaglinide + Losartan. The parameters like glycemic control, lipid profile, antioxidant status and progression of diabetic nephropthy before and after therapy was assessed by fasting blood sugar, glycated Hb, lipid profile, antioxidant status, renal function tests and proteinuria. From the group I & II comparisons our finding is that adding glimepiride or repaglinide to the basic regime of M + losartan has increased advantage and favorable effect. From comparison of group II & III finding is that repaglinide addition to the basic regime of M+ losartan had more favorable and increased advantage over glimepiride addition. The test for significant proteinuria and renal function tests was performed before enrollment and after completion of the study. After completion of the study no any patient was having significant proteinuria and all the patients have normal renal function tests. CONCLUSION: Losartan efficiently reduces proteinuria with adequate tolerance in presence of adequate glycaemic control. M + repaglinide + losartan combination is highly effective in controlling proteinuria. Several mechanisms may explain these effects. Although no glomerular hemodynamic parameters were analyzed in the present study, we consider that the attenuation of proteinuria reflects an improvement in the glomerular function. Losartan has been shown to reduce proteinuria by improving glomerular basement membrane characteristics. Losartan by targeting renin angiotensin aldosterone system improves overall glomerular function. This study is of interest since hypertension, which increases intra glomerular pressure and cause further progression of nephropathy, was similarly reduced with losartan administration.