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DISSERTATION ON “COMPARISON OF EFFICACY AND SAFETY OF BENIDIPINE WITH AMLODIPINE IN PATIENTS WITH UNCOMPLICATED HYPERTENSION - A PROSPECTIVE STUDY” Dissertation submitted to THE TAMILNADU Dr. M.G.R. MEDICAL UNIVERSITY In partial fulfillment of the requirement For the award of the degree of M.D. BRANCH-VI IN PHARMACOLOGY Submitted By Registration Number: 201716452 KARPAGA VINAYAGA INSTITUTE OF MEDICAL SCIENCES AND RESEARCH CENTRE, MADURANTHAGAM THE TAMILNADU Dr. M.G.R. MEDICAL UNIVERSITY, CHENNAI TAMILNADU MAY-2020 CERTIFICATE This is to certify that Dr. S. SRINATH, a Post Graduate student in the Department of Pharmacology has carried out the work titled “Comparison of efficacy and safety of Benidipine with Amlodipine in patients with uncomplicated hypertension” under the guidance of Dr. P. JACOB VERGHESE, M.D., PROFESSOR, Department of Pharmacology, towards the partial fulfillment of regulations laid down by The Tamilnadu Dr. M.G.R Medical University, Guindy, Chennai, Tamilnadu, India for the award of Doctor of Medicine (M.D.,) in Pharmacology. Dr.P. JACOB VERGHESE, M.D., DR. S. VIJAYALAKSHMI, M.D., PROFESSOR, PROFESSOR & HOD, Karpaga Vinayaga Institute of Karpaga Vinayaga Institute of Medical Medical Sciences & Research Centre, Sciences & Research Centre, Chinnakolambakkam, Chinnakolambakkam, MaduranthagamTk, MaduranthagamTk, Kancheepuram District– 603 308, Kancheepuram District– 603 308, Tamilnadu, India. Tamilnadu, India. DR. SUFALA SUNIL VISHWASRAO, PRINCIPAL, Karpaga Vinayaga Institute of Medical Sciences & Research Centre, Chinnakolambakkam, Maduranthagam Tk, Kancheepuram District– 603 308, Tamilnadu, India. DECLARATION I declare that dissertation entitled “Comparison of efficacy and safety of Benidipine with Amlodipine in patients with Uncomplicated Hypertension” submitted by me for the degree of M.D., is the record work carried out by me under the guidance of Dr. P. JACOB VERGHESE, Professor of Pharmacology, Karpaga Vinayaga Institute of Medical Sciences and Research Centre and has not formed the basis of any Degree, Diploma, Fellowship, titles in this or any other University or other similar Institution of Higher learning. Place: Chinnakolambakkam Signature of the Candidate Date: DR. S. SRINATH SIGNATURE OF GUIDE SIGNATURE OF HOD Dr.P. JACOB VERGHESE, M.D., DR. S. VIJAYALAKSHMI, M.D., PROFESSOR, PROFESSOR & HOD, Karpaga Vinayaga Institute of Karpaga Vinayaga Institute of Medical Medical Sciences & Research Centre, Sciences & Research Centre, Chinnakolambakkam, Chinnakolambakkam, MaduranthagamTk, MaduranthagamTk, Kancheepuram District– 603 308, Signature of the Guide Kancheepuram District– 603 308, Tamilnadu, India. Tamilnadu, India. ACKNOWLEDGEMENTS At the outset I express my sincere thanks to my esteemed guide Dr. P. JACOB VERGHESE M.D., Professor in the Department of Pharmacology, Karpaga Vinayaga Institute of Medical Sciences and Research Centre for his encouragement and valuable guidance in the topic given from time to time for the successful completion of study. I am extremely thankful to our Managing Director, Dr. ANNAMALAI, MS, MCH, Our Principal Dr. SUFALA SUNIL VISHWASRAO, M.D., our Medical Director Dr. SATHIYANARAYANAN, Karpaga Vinayaga Institute of Medical Sciences and Research Centre for providing me all the facilities to conduct this study. I express my deep and sincere gratitude to Dr. S. VIJAYALAKSHMI, M.D., Professor and Head, Department of Pharmacology, Karpaga Vinayaga Institute of Medical Sciences and Research Centre for being my mentor and support at all levels. I profusely thank my Co-guide Dr. S. APPANDRAJ, M.D., Professor, Department of General Medicine, Karpaga Vinayaga Institute of Medical Sciences and Research Centre for having permitted to conduct this study and the constant support he extended throughout the study. I thank Dr. R. KAVITHA, MD., Professor in the Department of Pharmacology, KarpagaVinayaga Institute of Medical Sciences and Research Centre for her kind guidance and encouragement during the course of this study. I express my deep and sincere gratitude to Dr. B. PRATHAP, M.D., Associate Professor, Department of Pharmacology, Karpaga Vinayaga Institute of Medical Sciences and Research Centre for his guidance and support at all levels. My heartfelt thanks to my Assistant Professors, Dr. E. SESHATHRI,M.D., and Dr. SUNIL M VISHWASRAO, M.D., in guiding me through the course of the study. I owe my sincere thanks to Dr. N. CHANDRAN, B.V.Sc., and AH for encouraging me towards this research. I thank my Senior and Junior Post Graduate colleagues for their greatest help and support throughout the course. I sincerely thank our bio-statistician GLADIUS JENIFER for her guidance during my dissertation. I am immensely grateful to the staffs at the Department of Pharmacology and Department of General Medicine, Karpaga Vinayaga Institute of Medical Sciences and Research Centre for having provided me technical support throughout the study. Last but no means the least, I am greatly indebted to all the patients who had taken part in this study without whom the study could not have been completed. Finally, my dissertation would have not been accomplished without the support of my father Mr. Samraj, My wife Dr. Radheka and my other family members. Above all I thank my Almighty for his blessings. CONTENTS CHAPTER PARTICULARS PAGE NO. 1 INTRODUCTION 1 2 AIMS AND OBJECTIVES 4 3 REVIEW OF LITERATURE 6 4 DRUG PROFILE 28 5 PLAN OF WORK 34 6 MATERIALS AND METHODS 36 7 OBSERVATION AND RESULTS 45 8 DISCUSSION 66 9 SUMMARY 73 10 CONCLUSION 76 11 BIBLIOGRAPHY 78 12 ANNEXURES 91 LIST OF TABLES S.NO TITLE PAGE NO 1 Classification of blood pressure in adults 8 2 Descriptive analysis of study group in study population 46 3 Comparison of mean age between study groups 46 4 Comparison of gender between study groups 48 Comparison of SBP at before drug treatment between study 5 49 groups Comparison of SBP at after drug treatment between study 6 51 groups Comparison of DBP at before drug treatment between study 7 53 groups Comparison of DBP at after drug treatment between study 8 55 groups 9 Comparison of ankle edema between study groups 57 Comparison of mean of serum creatinine between study 10 58 groups 11 Comparison of urine albumin between study groups 60 12 Comparison of mean difference of SBP between study groups 61 13 Comparison of mean difference of DBP between study groups 62 Comparison of SBP within groups before and after time 14 63 periods Comparison of DBP within groups before and after time 15 64 periods 16 Incidence of side effects 65 LIST OF FIGURES S.NO TITLE PAGE NO Systems involved in development and maintenance of blood 1 9 pressure 2 JNC 8 treatment guidelines for hypertension 15 Comparative error bar chart of comparison of mean age 3 47 between study groups 4 Stacked bar chart of comparison of gender between groups 48 Comparative error bar chart of comparison of SBP at before 5 50 drug between study groups Comparative error bar chart of comparison of SBP at after 6 52 drug between study groups Comparative error bar chart of comparison of DBP at before 7 54 drug between study groups Comparative error bar chart of comparison of DBP at after 8 56 drug between study groups Stacked bar chart of comparison of ankle edema between the 9 57 study groups Comparative error bar chart of comparison of serum 10 59 creatinine between study groups Stacked bar chart of comparison of urine albumin between 11 60 study groups LIST OF ABBREVIATIONS CCBs Calcium channel blockers JNC Joint national committee BP Blood pressure SBP Systolic blood pressure DBP Diastolic blood pressure CAD Coronary artery disease RAS Renin Angiotensin system CVA Cerebrovascular accident DHP Dihydropyridine IHD Ischemic heart disease LSM Life style modification CKD Chronic kidney disease CVD Cardiovascular disease ACE Angiotensin converting enzyme ARB Angiotensin receptor blocker FDC Fixed dose combination GFR Glomerular filtration rate SPSS Statistical package for the social sciences IQR Interquartile range 1. INTRODUCTION 1 1. INTRODUCTION Hypertension, a chronic medical condition which is more prone to cause cardiovascular diseases remains a global burden. Around 1.13 billion people worldwide are affected by hypertension till 20151, which is expected to be growing by 2020.Around 29.8% population in India are suffering from hypertension2. Since it is a major risk factor for cardiovascular mortality and other non-communicable diseases3, treatment studies on hypertension are effectively to be made. Dietary and lifestyle modifications may improve blood pressure control, but along with drug treatment there is major decline in the complications that are associated with hypertension. All major classes of antihypertensive like diuretics, CCBs, beta blockers, ACEIs, ARBs are most suited for long term therapy either in combination or alone4.Inspite of advent of many drugs for the control of hypertension, it remains the most common aggravating factor for cardiovascular diseases and controlling blood pressure effectively still remains a milestone in medical research4. Calcium channel blockers (CCB) are nowadays widely used in the treatment of hypertension according to the JNC guidelines as a first choice because of their ability to reduce blood pressure effectively with minimal cost. CCBs disrupt the movement of calcium ions through calcium channels in the large vessels, thereby reducing their arterial stiffness which makes them an ideal choice for elevated systolic blood pressure. Among the Dihydropyridine group of calcium channel blockers, Amlodipine
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  • Benidipine Reduces Albuminuria and Plasma Aldosterone in Mild-To-Moderate Stage Chronic Kidney Disease with Albuminuria

    Benidipine Reduces Albuminuria and Plasma Aldosterone in Mild-To-Moderate Stage Chronic Kidney Disease with Albuminuria

    Hypertension Research (2011) 34, 268–273 & 2011 The Japanese Society of Hypertension All rights reserved 0916-9636/11 $32.00 www.nature.com/hr ORIGINAL ARTICLE Benidipine reduces albuminuria and plasma aldosterone in mild-to-moderate stage chronic kidney disease with albuminuria Masanori Abe1, Kazuyoshi Okada1, Noriaki Maruyama1, Shiro Matsumoto1, Takashi Maruyama1, Takayuki Fujita1, Koichi Matsumoto1 and Masayoshi Soma1,2 Benidipine inhibits both L- and T-type Ca channels, and has been shown to dilate the efferent arterioles as effectively as the afferent arterioles. In this study, we conducted an open-label and randomized trial to compare the effects of benidipine with those of amlodipine on blood pressure (BP), albuminuria and aldosterone concentration in hypertensive patients with mild-to- moderate stage chronic kidney disease (CKD). Patients with BPX130/80 mm Hg, with estimated glomerular filtration rate (eGFR) of 30–90 ml minÀ1 per 1.73 m2, and with albuminuria430 mg per g creatinine (Cr), despite treatment with the maximum recommended dose of angiotensin II receptor blockers (ARBs) were randomly assigned to two groups. Patients received either of the following two treatment regimens: 2 mg per day benidipine, which was increased up to a dose of 8 mg per day (n¼52), or 2.5 mg per day amlodipine, which was increased up to a dose of 10 mg per day (n¼52). After 6 months of treatment, a significant and comparable reduction in the systolic and diastolic BP was observed in both groups. The decrease in the urinary albumin to Cr ratio in the benidipine group was significantly lower than that in the amlodipine group.