Resistant Hypertension- A Review of Management Strategies

Resistant hypertension (RH) is defined as the condition in which the blood pressure remains above goal in spite of concurrent use of 3 antihypertensive agents of different classes. Prevalence of resistant hypertension is 10-20% of the general hypertensive population. Patients with resistant hypertension are at high risk for adverse cardiovascular events. After excluding pseudoresistance, two most important causes of resistant hypertension are concomitant use of drugs and secondary causes. Management includes careful selection of antihypertensive drugs, lifestyle changes, treatment of secondary causes of hypertension, and discontinuation/ minimizing drugs that can cause hypertension. Invasive treatment option at present is an era to be explored

Designing and Synthesis of Flavonoids Derivatives and Screening of their Antioxidant Activity

The flavonoids present in red wine were responsible this low cardiovascular mortality rate. Epidemiologic studies further suggest that dietary flavonoids are useful to control and protect the CHD. The flavonoids are yellow color substance (pigments) and the name given on the basis of Latin term Flavus which means yellow color. Flavonoids are derivatives of benzo-pyrone. Banzopyrone is a group of heterocyclic aromatic oxygen containing compounds. Finely powdered zinc chloride (8.25) was dissolved in glacial acetic acid (18ml)  by heating on sand bath then dry resorcinol (appx.5.5 gm) was added with  continuous  stirring to the mixture at  1400C. Antioxidant Screening by hydrogen peroxide scavenging assays. Hydrogen peroxide solution (40 mini moles) was prepared with standard phosphate buffer of pH 7.4. Different concentration of the compound stock solution and 4ml distilled water was added to 0.6 ml of hydrogen peroxide solution. UV absorbance was determined at the wavelength of 230 nm after 10 min with a blank solution containing phosphate buffer without H2O2. Take 4 ml different concentration of sample solution and 1ml sodium nitroprusside solution, added and incubated for 2.5 hrs at 370C. After incubation baseline was taken with methanol and 1ml sodium nitroprusside solution as blank solution. Griess reagent and methanol was added immediately before recording of readings. The readings were recorded at 546nm wavelenth. In the series of synthesized and evaluated compounds of Flavanoid electron withdrawing group at position four shows good activity. 2,3-dihydroflavan-3-ol derivatives showed lower activity than that of 3- hydroxyflavone derivatives. The 4-oxo (keto double bond at position 4 of the C ring), especially in association with the J2-J3 double bond, increases scavenger activity by delocalizing electrons, 3-hydroxy group on the C ring generates an extremely active scavenger; the combination of J2-J3 double bond,3-hydroxy group and 4-oxo group appears to be the best combination for potent antioxidant activity. Keywords: Flavonoids, Antioxidant activity, Hydrogen peroxide scavenging, free radical

Detection of Congenital Heart Disease by Fetal Echocardiography and Its Correlation with Karyotype

Background: Congenital heart diseases (CHDs) account for a third of all major congenital abnormalities in children; nearly 1,80,000 children are born with heart defect each year in India. Approximately, 10% of present infant mortality in India may be attributed to CHD alone. Such high mortality is due to laying less emphasis on its prenatal diagnosis by fetal echocardiography. This study was done with objectives to find out the incidence of CHD in high risk cases and its correlation with karyotype and also evaluating the diagnostic accuracy of fetal echocardiography. Methods: Fetal echocardiography was performed in 142 high risk cases who attended antenatal clinic of Institute of Medical Sciences (IMS), Banaras Hindu University (BHU), Varanasi between July 2014 to June 2016 with maternal/fetal risk for CHD (maternal diabetes mellitus, collagen disorders, teratogen exposure, maternal TORCH infection, in vitro fertilization [IVF] conceived pregnancy, familial history of CHD, abnormal four-chamber view, monochorionic twins). Results: The incidence of major CHD was 28/1,000 live births and 56/1,000 live births for minor CHD in high risk group. Ventricular septal defect (16.6%) and hypoplastic left heart syndrome (16.6%) were the most common CHD detected. Family history of CHD increases the risk significantly. Fetal echocardiography was 75% (46.77-91.11, 95% confidence interval [CI]) sensitive and 94.5% (89.22-97.35, 95% CI) specific, with 92.91% (87.44-96.1, 95% CI) diagnostic accuracy. It was seen that 16.6% cases of CHD had aneuploidy detected on karyotyping (trisomy 21 and trisomy 18). Conclusion: Fetal echocardiography is highly sensitive and specific, when done by an experienced operator. Prenatal diagnosis of CHD and planned delivery in a cardiac facility had satisfactory immediate outcomes

Designing and Synthesis of Flavonoids Derivatives and Screening of their Antimicrobial Activity

Antimicrobial drugs either kill microbes (microbicidal) or prevent the growth of microbes (microbistatic). The streptococcus mutans is a bacteria that found in the human mouth cavity. This bacterial strain produces plaque and acids that break down tooth enamel and cause dental caries. Gram positive cocci, facultatively anaerobic bacteria that forms rod-like chains. the chemical reaction of 2- hydroxyacetophenones with aromatic acylchloride occurs to form 1,3-diketones. This rearrangement reaction proceeds via enolate formation followed by acyl transfer. Then it cyclises into flavone.13 As the same of above scheme can be worked out as 2- Methoxybenzoyl Chloride is prepared by reaction of 2- methoxybenzoic acid  with  Thionyl chloride and DMF. 2-Methoxybenzoyl Chloride then added to mixture of 2- hydroxyacetophenone and pyridine, 2-[(2-Methoxybenzoyl)oxy]acetophenone thus obtained is treated with pyridine and KOH which gives1-(2-Hydroxyphenyl)-3-(2- methoxyphenyl)-propan1,3-dione. The result of study indicated that C5 [1-(2- hydroxyphenyl)-5-phenylpenta-2,4-dien-1-one]; is only inactive against Streptococcus mutans. All 3-hydroxyflavone derivatives exhibited their MIC to be in range of 250-125 µg/ml., 2,3-dihydroflavan-3-ol derivatives exhibited their MIC to be in  range of  1000- 500 µg/ml. The chalcone derivatives exhibited their MIC to be at 250 µg/ml. Keywords: Streptococcus mutans, flavonoids derivatives, MIC, 2,3-dihydroflavan-3-ol

Synthesis and Evaluation of Aldehyde Derivatives of Sulfonyl Chloride Quinoxaline

In pyrazine mesomeric interaction between the protonated & neutral nitrogen atoms probably destabilizes the cation.N, N’-diprotonation is very easier for pyrazine Synthesis of 2, 3-diphenylquinoxaline by phenylene-diamine in 16 ml of rectified spirit was added & combine solution was warm in water bath for 30 min. added water until slight colorless persist & allow to cool recrystallize the product in ethanol.   Synthesis of 2, 3-diphenylquinoxaline 7-sulfonylchloride (R) using chlorosulfonic acid under ice-cold condition, then Synthesis of  2-hydroxyphenyl-2,3-diphenylquinoxaline-7-sulphonate(R1) throughresorcinol with 3ml pyridine & sulphonyl chloride derivative, Synthesis of 2-formylphenyl-2,3-diphenylquinoxaline-7-sulphonate(R7)obtained by reaction of salicylaldehyde with pyridine & sulphonyl chloride derivative then Synthesis of 3-formylphenyl-2,3-diphenylquinoxaline-7-sulphonate(R9) obtained by heating on water bath mixture of3-hydroxybenzaldehyde with pyridine & sulphonyl chloride, Synthesized quinoxaline derivatives were subjected to antimicrobial susceptibility testing by well diffusion method against gram positive (S.aureus, 2079) and gram negative bacteria (E. coli, 2685). The results of quinoxaline derivatives in terms of zone of inhibition recorded. MIC of quinoxaline derivative was determined by tube micro dilution technique against S. aureus and E. coli. The turbidity was measured by UV at about 420 nm. Hydrogen peroxide scavenging activity and 1, 1 diphenyl 2, picryl hydrazyl Method (DPPH) calculated and Most of the derivatives have shown comparable antioxidant activity in relation to standard Ascorbic acid and DPPH.  Keywords: QSAR, Sulfonyl Chloride Quinoxaline, Ant-microbial, Antioxidan

Synthesis and Anti-Oxidant Activity of Phenol and Aldehyde Derivatives of Sulfonyl Chloride Quinoxaline

N, N’-diprotonation is very easier for pyrazine Synthesis of 2, 3-diphenylquinoxaline by phenylene-diamine in 16 ml of rectified spirit was added & combine solution was warm in water bath for 30 min. added water until slight colorless persist & allow to cool recrystallize the product in ethanol.   Synthesis of 2, 3-diphenylquinoxaline 7-sulfonylchloride (R) using chlorosulfonic acid under ice-cold condition, thenSynthesis of  2-hydroxyphenyl-2,3-diphenylquinoxaline-7-sulphonate (R1) throughresorcinol with 3ml pyridine &sulphonyl chloride derivative, Synthesis of 2-formylphenyl-2,3-diphenylquinoxaline-7-sulphonate (R7)obtained by reaction of salicylaldehyde with pyridine &sulphonyl chloride derivative then Synthesis of 3-formylphenyl-2,3-diphenylquinoxaline-7-sulphonate (R9) obtained by heating on water bath mixture of 3-hydroxybenzaldehyde with pyridine &sulphonyl chloride, Synthesized quinoxaline derivatives were subjected to antioxidant activity.Hydrogen peroxide solution (40 mM) was prepared with standard phosphate buffer (pH 7.4). Different concentration of the compound stock solution and 4ml distilled water was added to 0.6 ml of hydrogen peroxide solution. Absorbance was determined at 230 nm after 10 min against a blank solution containing phosphate buffer without hydrogen peroxide. DPPH radical scavenging activity was measured using the method of Cotelleet al. with some modifications. 3 ml of reaction mixture containing 0.2 ml of DPPH (100 μM in methanol) 2.8 ml of test solution, at various concentrations (5, 10, 20, 40, 80, 160 320 μg/ml) of the extract fractions was incubated at 37°C for 30 min absorbance of the resulting solution was measured at 517 nm using Beckman model DU-40 spectrophotometer. Most of the derivatives have shown comparable antioxidant activity in relation to standard Ascorbic acid and DPPH Keywords: DPPH,Quinoxaline, Antioxidant activity,Sulfonyl chloride quinoxaline

Synthesis and Evaluation of Phenol Derivatives of Sulfonyl Chloride Quinoxaline

The objective of the present study was to synthesize some new 7-sulfonate of 2, 3- Diphenyl quinoxaline which are more potential as antibacterial than parent quinoxalines. The present study was synthesis of derivatives of sulfonyl chloride quinoxaline and physicochemical and spectral characterization, in vitro antimicrobial screening against gram positive and gram negative bacteria.The concentration of derivatives used as 200 and 400 microgram initially. When 200 µg concentrations was used R6 shows sensitivity towards S. aureus and R6 shows sensitivity towards gram negative E. coli organism. When 400 µg used then R3, R5, and R6 shows sensitivity in case of gram positive organism. And in case of gram negative organism R5, R6 shows sensitivity.Azithromycin is used as Reference drug and a comparative study was done. As compare to reference drug all derivatives shows less sensitivity than S- Standard and R- quinoxaline derivatives. Keywords: Diphenyl quinoxaline, QSAR, Quinoxaline, Phenol derivative

Formulation Development and Evaluation of Floating Microsphere of Famotidine for the Treatment of Peptic Ulcer

The purpose of this research was to prepare a floating drug delivery system of famotidine. The floating microspheres can be prepared for the improvement of absorption and bioavailability of famotidine by retaining the system in the stomach for prolonged period of time. Floating microspheres of famotidine were prepared using different polymers like ethyl cellulose, hydroxy propyl methyl cellulose by solvent diffusion-evaporation method. The microspheres had smooth surfaces with free-flowing and good-packing properties. The yield of the microspheres was up to 73.32±0.14% and ethyl cellulose microspheres entrapped the maximum amount of the drug. Scanning electron microscopy confirmed their hollow structures with sizes in 331.6 nm. The prepared microspheres exhibited prolonged drug release and Percentage buoyancy was found to 73.25±0.23. The formulated batches were evaluated for percentage yield, particle size measurement, flow properties, percent entrapment efficiency, swelling studies. The formulations were subjected to stability studies and In-vitro release and release kinetics data was subjected to different dissolution models. It was concluded that developed floating microspheres of famotidine offers a suitable and practical approach for prolonged release of drug over an extended period of time and thus oral bioavailability, efficacy and patient compliance is improved. Keywords: Famotidine, Solvent diffusion evaporation method, Ethyl cellulose, Hydroxyl propyl methyl cellulos

FORMULATION, DEVELOPMENT AND EVALUATION OF BI-LAYER TABLET OF ANTI HIV DRUG

In the last decade, interest in developing a combination of two or more Active Pharmaceutical Ingredients (API) in a single dosage form (bi-layer tablet) has increased in the pharmaceutical industry, promoting patient convenience and compliance. The Bi-layer tablets have been developed to achieve controlled delivery of different drugs with pre-defined release profiles. Bi-layer tablets can be a primary option to avoid chemical incompatibilities between API by physical separation, and to enable the development of different drug release profiles (immediate release with extended release). Despite their advantages, due to the use of different materials and complex geometric boundaries between the adjacent layers, the mechanical structures of this drug delivery system have become quite intricate, requiring complicated tablet architectures as well as patient-friendly. Bi-layer tablets offer definite advantages over conventional release formulation of the same drug. Several pharmaceutical companies are currently developing bi-layer tablets. For a variety of reasons: patent extension, therapeutic, marketing to name a few. To reduce capital investment, quite often existing but modified tablet presses are used to develop and produce such tablets. Key words: Bi-layered tablet, API (Active Pharmaceutical Ingredients), adjacent layer, conventional release, insufficient hardness

Real-world clinical experience of ticagrelor in Indian patients with acute coronary syndrome after discharge from a tertiary setting

Background: To understand the usage pattern of ticagrelor in real-life clinical experience in Indian patients with the acute coronary syndrome (ACS) after discharge from a tertiary care setting. Methods: A retrospective multicentric observational study conducted across Indian healthcare centers having medical records of adult patients with ACS. Patients prescribed with ticagrelor post-discharge for at least 1 month were included. The study endpoints were to determine the clinical effectiveness of ticagrelor in post-ACS patients and adverse events reported during the study period. Results: A total of 1910 patients with ACS with a mean (SD) age of 58.2 (11.3) years were enrolled in this study. The median (IQR) duration of treatment was 30.0 (30.0-90.0) days. More than half of the patients (n=1115, 58.4%) were managed with interventional therapy. The most common comorbid conditions were type-2 diabetes mellitus (46.9%), followed by hypertension (36.8%). A total of 9.7% of patients reported complaints after treatment with ticagrelor. Among them, weakness, giddiness, and body pain were the most common (3.2%). Conclusions: This real-world study revealed that ticagrelor had been used widely in patients who underwent different management strategies. History of diabetes and hypertension were the most common risk factors. There were no major adverse events reported during the follow-up, indicating ticagrelor is well-tolerated in Indian patients with ACS