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Sub-Chronic Effect Of Co-Administration Of Methformine and Amilodipine on Some Haematological Indices in Experimental Animal

Sub-Chronic Effect Of Co-Administration Of Methformine And Amilodipine On Some Haematological Indices In Experimental Animal (Wistar Rats) is a complete project material for download.

TABLE OF CONTENT

Title page

Declaration

Certification

Dedication

Acknowledgement

Table of content

List of table

List of figures

Abstract

CHAPTER ONE

1.0 Introduction

1.1 Background of study

1.2 Statement of Problems

1.3 Justifications

1.4Aims

1.5Research Objectives

1.6Research Hypothesis

1.7 Significance of research

CHAPTER TWO

2.0 Literature review

2.1Metformin

2.1.1 Mechanism of metformin

2.1.2 Pharmacological properties of metformin

2.1.3 Side effects and contra-indications of metformin

2.1.4 Therapeutic application of metformin

2.2 Vitamin B12: biochemistry, deficiency and anaemia

2.3 Relationship between metformin and vitamin B12

2.4 Metformin and haemolytic anaemia

2.5 Diagnosis of anaemia

2.6 Efficacy of Metformin

2.7 Amlodipine

2.7.1 Chemistry

2.7.2 Mechanism of action

2.7.3 Side effects

2.7.4 Pharmacokinetics

2.8 Angiotensin Converting Enzyme Inhibitors

2.9 Reference range of haematological parameters of rats

2.10 Comparative haematology of rat and human

CHAPTER THREE

3.1 Study Design

3.2 Preparation of animals

3.3 Sample size determination

3.4 Reagent Kits/Drug Preparation and Dosage

3.5 Dosage

3.6 Sample collection

3.7 Measurement of variables                                                             .

3.8 Ethical consideration

3.9 Statistical analysis

CHAPTER FOUR

4.1 Result

42.Differential white blood cell counts in controls and tests groups

CHAPTER FIVE

5.0 Discussion

5.1 Conclusion

5.2 Recommendation

References

Appendix I

Appendix II

ABSTRACT

Metformin, which belongs to the biguanide class, is one of themost generally used oral hypoglycemic agents. It has been used formore than 50 years and was approved by the US Food and DrugAdministration (FDA) in 1994 (American Diabetes Association, 2009) whereas Amlodipine is a long acting dihydropyridine calcium channel blocker, which is used in thetreatment 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. To assess the MCV,MCH,MCHC level of experimental animal and that of control group after combined administration with amilodipine and metformin.

Animals were randomly grouped into Two (A and B) groups,each groups contains eight (8) animals.Group A was administered normal saline; Group B was administered combined administration with amilodipine (0.00264mg/ml/132g) and metformin(0.0438mg/ml/132g) once dailyfor 30days after 2 weeks of acclamatization.

Each group of rats was allowed to have free access to waterad libitumand standard rat chow (SRC) throughout the experimental period. Blood was collected from the Jugular vein at the end of the experiment to determine the full blood count of each animal.

There was a significant reduction (p≤0.05) in hemoglobin level, RBC, PCV and increase in WBC and decrease in PLT count, and with increase in MCV, MCH with no difference in MCHC after co-administration of Metformin and Amlodipine in Wistar Rat as compared to control.

These findings suggests that Co-administration of Metformin and Amlodipine causes decrease in red cell dependent parameters gradually leading to anaemia with long term usage thus regarded as a hematotoxicity agent to the blood profile.

Key words: Metformin, Amlodipine, haematological parameters, Wistar Rats.

CHAPTER ONE

INTRODUCTION

1.1 Background of the study

Metformin, which belongs to the biguanide class, is one of themost generally used oral hypoglycemic agents. It has been used formore than 50 years and was approved by the US Food and DrugAdministration (FDA) in 1994 (American Diabetes Association, 2009).

Currently, many clinicalpractice guidelines for patients with type 2 diabetes, including theAmerican Diabetes Association (ADA), the European Associationfor the Study of Diabetes (EASD), and the Korean DiabetesAssociation (KDA), recommend that metformin treatment shouldbegin at the time of diagnosis of diabetes with lifestyle modificationin the absence of contraindications.

Metformin is now the most widely used anti-diabetic drug, withalmost all guidelines throughout the world recommendingmetformin as first-line treatment for patients with type 2 diabetesmellitus (T2DM). Metformin may also be used to treat otherconditions involving insulin resistance, such as polycystic ovarysyndrome (PCOS) (Boyleet al., 2010).

Metformin has beneficial effects oncarbohydrate metabolism, weight loss, and vascular protection but also has important side effects. For example, patients onlong-term metformin therapy were found to be at risk of anaemia (Maidaet al., 2011). This may be due to a metformin related vitamin B12reduction. It is reported that, 30% of patients receiving long-termmetformin treatment experienced malabsorption of vitamin B12,with a decrease in serum vitamin B12 concentration of 14% to30% (Burcelin, 2014).

It was therefore imperative to investigate the effect of co-administration of metformin and amilodipine on some hematological parameters in experimental animal (Wistar Rats).

1.2 Statement of problem

Drug-drug interactions are a major problem in health facilities the world over. The prevalence of interactions is estimated to be between 1- 22% (Lakshmi et al., 2015). Underlying risk factors for drug-drug interactions include polypharmacy and co-morbid conditions.

High blood pressure in patients with diabetes presents a major health problem because of increased risk of polypharmacy. Polypharmacy leads to prescribing drugs that may have drug interactions. The interactions can lead to life threatening situations, hospitalization, increased burden to patients, hematotocixitiy (anaemia either haemolytic or vitamin B12 deficiency) as well assuppression of bone marrow activity from calcium blocker mechanism of antihypertensive drugs and adjusted quality of life.

A considerable number of the drug-drug interactions can be avoided if health workers involved in patient care have the right information. Various hospitals and clinics serves patients from various regions that visit the facility for various ailments including diabetes and hypertension which


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