TABLE OF CONTENTS

PAGE

TITLE PAGE        –         –         –         –         –         –         –         –         i

CERTIFICATION            –         –         –         –         –         –         –         ii

DEDICATION       –         –         –         –         –         –         –         –         iii

ACKNOWLEDGEMENTS       –         –         –         –         –         –         iv

TABLE OF CONTENT   –         –         –         –         –         –         –         v

CHAPTER ONE: INTRODUCTION          –         –         –         –         1

CHAPTER TWO: ANTIBIOTICS

2.1     Classification of Antibiotics       –         –         –         –         –         3

2.1.1  Beta-lactams          –         –         –         –         –         –         –         4

2.1.2  Macrolides   –         –         –         –         –         –         –         –         6

2.1.3  Quinolones –         –         –         –         –         –         –         –         8

2.2     Mode of Action of Antibiotics   –         –         –         –         –         9

2.2.1  Inhibition of Cell Wall Synthesis         –         –         –         –         9

2.2.2  Breakdown of the Cell Membrane Structure or Function   –         10

2.2.3  Inhibition of Nuclei Acid Synthesis     –         –         –         –         11

2.2.4  Inhibition of Protein Synthesis –         –         –         –         –         11

2.2.5 Blockage of Key Metabolic Pathways –         –         –         –         14

2.3     Signs and Symptoms of Hepatotoxic   –         –         –         –         14

CHAPTER THREE: HEPATO EFFECT OF SOME

 ANTIBIOTICS    –         –         –         –         –         –         –

3.1     Penicillin      –         –         –         –         –         –         –         –         16

3.2     Amoxicillin/Clavulanate  –         –         –         –         –         –         18

3.3     Cephalosporins      –         –         –         –         –         –         –         19

3.4     Erythromycin        –         –         –         –         –         –         –         19

3.5     Ciprofloxacin –      –         –         –         –         –         –         –         21

3.6     Tetracyclines          –         –         –         –         –         –         –         22

3.7     Use of Antibiotics in Liver Disease      –         –         –         –         23

CHAPTER FOUR: SUMMARY AND CONCLUSION

4.1     Summary     –         –         –         –         –         –         –         –         28

4.2     Conclusion  –         –         –         –         –         –         –         –         29

References

CHAPTER ONE: INTRODUCTION

Antibiotic-induced hepatotoxicity is usually asymptomatic, transient and associated with only mild hepatic impairment (Thiim and Friedman, 2003). In rare cases, however, significant morbidity the need for liver transplantation and death from acute liver failure have been reported. In recent years, the European Medicines Agency (EMA) and the US FDA have addressed these issues by putting emphasis on both pre-clinical (to detect signals) and clinical studies (Hughes, 2008). Nonetheless, predicting what hepatotoxicity will be after approval based on data assembled during drug development remains a risky exercise.

Public awareness of antibiotic-induced hepatotoxicity has, however, increased over recent years (following actions of regulatory bodies targeting specific antibiotics) making it essential for the primary care physician to better identify and minimize the risk of serious liver damage with existing agents (Thiim and Friedman, 2003). In the present review, we describe the adverse hepatic effects of antibiotics, including their frequency, severity and clinico-pathological features, and discuss these observations within the context of the primary care setting. Indeed, this is not only where antibiotic consumption is greatest but also where risks are highest, given the inherent difficulties of rapid access to in-depth biological investigations for prompt diagnosis (Gossens et al., 2005).