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Sub-chronic Effect Of Co-administration Of Methformine And Amilodipine On Some Haematological Indices In Experimental Animal
[A CASE STUDY OF WISTAR RATS]
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2.7.2 Mechanism of action
Amlodipine inhibits the transmembrane influx of calcium ions into vascular smooth muscle (Zankat et al., 2015). and lowers the blood pressure by relaxing arterial smooth muscles, in turn decreasing the total peripheral resistance and thus reduces blood pressure. The drug is considered to be most important medication needed in basic health system, listed by WHO’s list of essential medicines (WHO, 2013). It is used in the treatment of coronary heart disease and in the management of hypertension (Wang et al., 2009).
2.7.3 Side Effects
There are some adverse effects resulted from Amlodipine intake, but most of them were of mild to moderate severity. The most common adverse reactions in controlled clinical trials were edema, which observed in 8.9% of drug users and 8.3% of the users experience headache. (Lakshmi et al., 2015). One percent (1%) of drug users undergoes mild side effects such as dizziness, palpitations, stomach pain, dyspepsia, somnolence and nausea (Lakshmi et al., 2015).
2.7.4 Pharmacokinetics
Amlodipine is slowly but completely absorbed after oral administration of therapeutic doses, with moderately high bioavailability (64%–90%) which is not altered by presence of food. Absorption occurs gradually with peak plasma concentration reached between 6 and 12 hours. This drug is extensively converted to inactive metabolites via hepatic metabolism, with 10% of the parent compound and 60% of the metabolites excreted in the urine (Lee et al., 2015). Ex-vivo studies have shown that approximately 93% of the circulating drug is bound to plasma proteins in hypertensive patients. Amlodipine is predominantly metabolized by cytochrome P450 family member cytochrome P450 (CYP) 3A4 in liver (Guo et al., 2015). Elimination from the plasma is biphasic with a terminal elimination half-life of about 35-50 hours. Steady state plasma levels of amlodipine are reached after 7 to 8 days of consecutive daily dosing (Lakshmi et al., 2015).
2.8 Angiotensin Converting Enzyme Inhibitors
ACE is a zinc metallopeptidase expressed at the surface of many cells where it catalyzes the conversion of Angiotensin I to Angiotensin II and degrades Bradykinin, a potent vasodilator
(Ribeiro-Oliveira et al., 2008). Angiotensin II produces renal vasoconstriction and antinatriuresis, which together lead to elevating blood pressure (Berra and Miller, 2009). Release of renin by the kidney results in activation of and lead to many physiological renal and CV events. Renin catalyzes the formation of angiotensin I, which is then converted to angiotensin II by angiotensin converting enzyme (ACE), resulting in activation of the angiotensin II receptors, which effect on renal vasculature, resulting in CKD. Therefore, targeting RAS is a logical approach to reducing renovascular risk (Fliser, 2010).
ACEIs are commonly used in the treatment of CV disorders. The use of these agents for HTN and heart failure is well established and has proven to reduce morbidity and mortality, although these agents have not proven to be superior to other antihypertensive agents. ACEIs are now routinely used in myocardial infarction patients to reduce re-infarction and mortality risk, and are combined with a diuretic for secondary prevention in stroke patients (Chua et al., 2011). Currently, many ACEIs have been approved for use and already marketed worldwide (ex. Captopril, Enalapril, Cilazapril, Lisinopril, and Ramipril). Most of these drugs are considered to be pro-drugs (Wishart et al., 2008).
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ABSRACT - [ Total Page(s): 1 ]ABSTRACTMetformin, which belongs to the biguanide class, is one of the most generally used oral hypoglycemic agents. It has been used for more than 50 years and was approved by the US Food and Drug Administration (FDA) in 1994 (American Diabetes Association, 2009) whereas Amlodipine is a long acting dihydropyridine calcium channel blocker, which is used in the treatment of angina to lower the BP (Blood pressure). the aim is to know the effect of co-administration of this two drugs in Wistar rats ... Continue reading---
APPENDIX A - [ Total Page(s): 1 ]APPENDIXAPPENDIX 1: MATERIAL USED1% Ammonium oxalate10% Formalin salineAbsorbent paperAutomatic pipetteBrilliant cresyl blueCounting chamber Cyanmethaemoglobin standardDrabkin’s ReagentEDTA sample containerHematoxylin and Eosin stainKhan tubes/rackLeisfhmann stainLight microscopeMicrohaematocrit centrifugeNormal salinePasteur pipettePipette tipsRotary microtomeSpectrophotometerTimer Turk’s solution Universal sample bottle ... Continue reading---
APPENDIX B - [ Total Page(s): 1 ]APPENDIX IITable 1: haematological parameters in control, Metformine treated and Amilodipine treated Rats (Values are expressed as mean ± Standard error of means) Group A(1): control (untreated), Group B(2): co-administration of Metformin 0.00264/ml/132g and Amlodipine 0.000849/ml/132g at a single dose for 30 daysPARAMETERS GROUP A GROUP BPacked cell volume (%) 44.16±2.83 38.47±3.53Red blood cell count (x1012/L) 7 ... Continue reading---
LIST OF TABLES - [ Total Page(s): 1 ]LIST OF TABLESTable 1: Haematological parameters in control, Co-administration of Metformin and Amlodipine treated ... Continue reading---
LIST OF FIGURES - [ Total Page(s): 1 ]LIST OF FIGURESFigure 1: Shows mechanism of action of metformin Figure 2: Shows Pie chat representation of Packed cell volume of control, Co-administration of metformin and amlodipine treated Wistar Rats Figure 3: Shows Histogram representation of Hemoglobin and red blood cell count of control, Co-administration of metformin and amlodipine treated Wistar Rats Figure 4: Shows Histogram representation of red cell indicies of control, Co-administration of metformin and amlodipine t ... Continue reading---
TABLE OF CONTENTS - [ Total Page(s): 1 ]TABLE OF CONTENTTitle page Declaration Certification Dedication Acknowledgement Table of content List of table List of figures Abstract CHAPTER ONE1.0 Introduction 1.1 Background of study 1.2 Statement of Problems 1.3 Justifications 1.4 Aims 1.5 Research Objectives 1.6 Research Hypothesis 1.7 Significance of research CHAPTER TWO2.0 Literature review 2.1 Metformin 2.1.1 ... Continue reading---
CHAPTER ONE - [ Total Page(s): 2 ]CHAPTER ONE1.0 INTRODUCTION1.1 Background of the studyMetformin, which belongs to the biguanide class, is one of the most generally used oral hypoglycemic agents. It has been used for more than 50 years and was approved by the US Food and Drug Administration (FDA) in 1994 (American Diabetes Association, 2009). Currently, many clinical practice guidelines for patients with type 2 diabetes, including the American Diabetes Association (ADA), the European Association for the Study of Diabetes ... Continue reading---
CHAPTER THREE - [ Total Page(s): 4 ]From the above table,Km of rats= 6 Km of human= 37For Amlodipine, Human dose= 10mg/70kg 1kg=10/70 =0.14mg/kgAED of Amilodipine= 0.14×(6/37) =0.02mg/kgAverage weight of experimental Animal is 132g(0.132kg)If 0.02mg of Amlodipine is administered per kg.bw,(0.02×0.132)mg of Amlodipine was administered to ... Continue reading---
CHAPTER FOUR - [ Total Page(s): 6 ]CHAPTER FOUR4.0 Results4.1 Hematological parameter in control and test groups As summarized in table 1, the mean RBC counts were 7.62 ± 2.83 x1012/L for the control and 6.53 ± 0.57 x1012/L for co-administration of metformin and amlodipine fed groups respectively. Although, decrease in RBC counts was observed in the treated (co-administration of metformin and amlodipine) dose group, these were statistically significant compared to control groups (student t test P0.05) higher in the tr ... Continue reading---
CHAPTER FIVE - [ Total Page(s): 2 ]CHAPTER FIVE5.0 DiscussionMetformin (1,1-dimethylbiguanide) is the most widely used drug to treat type 2 diabetes, and is one of only two oral anti-diabetic drugs on the World Health Organization (WHO) list of essential medicines (American Diabetes Association, 2009). Amlodipine is a long acting dihydropyridine calcium channel blocker, which is used in the treatment of angina to lower the BP. Co-administration of Metformin and Amlodipine have been discovered to lead to vitamin B12 deficiency. Al ... Continue reading---
REFRENCES - [ Total Page(s): 4 ]Senol, M.G., Sonmez, G., Ozdag, F. and Saracoglu, M. (2008). Reversible myelopathy with vitamin B12 deficiency. Singapore Medical Journal. 49(11): 330-332.Srinivasan, S., Ambler, G.R., Baur, L.A., Garnett, S.P. and Tepsa, M. (2006). Randomized, controlled trial of metformin for obesity and insulin resistance in children and adolescents: improvement in body composition and fasting insulin. Journal of Clinical Endocrinology and Metabolism. 91: 2074-2080. Sterne, J. (1957). Du nouveau dans les anti ... Continue reading---
