Efflux pump mechanisms perform important physiological functions such as prevention of toxin absorption from the gastrointestinal tract, elimination of bile from the hepatocytes, effective functioning of the blood–brain barrier and placental barrier, and renal excretion of drugs. They exist in all living cells, but those in the bacterial and mammalian cells are more important to the clinician and pharmacologist, as they constitute an important cause of antimicrobial drug resistance, which contributes to treatment failure, high medical bills, and increased mortality / morbidity. This review was aimed at highlighting the role of efflux pump mechanisms in microbial resistance to chemotherapeutic agents. It was also aimed to elucidate their structure and mechanisms of action so as to integrate the efflux pump mechanisms in the design and development of novel antimicrobial agents. Findings from previous studies and research on this subject assessed through Google search, Pubmed, Hinari websites, as well as standard textbooks on chemotherapy, provided the needed information in the process of this review. Efflux pump inhibitors are promising strategies for preventing and reverting efflux-mediated resistance to chemotherapeutic agents. They are usually employed as adjuncts in antimicrobial and cancer chemotherapy. Toxicity, more common with the older-generation inhibitors such as verapamil and reserpine, constitutes the greatest impediment to their clinical applications. No efflux pump inhibitor has been approved for routine clinical use, as a result of doubtful clinical efficacy and unacceptably high incidence of adverse effects, particularly inhibition of the P-450 drug metabolizing enzyme. At present, their applications are mainly restricted to epidemiological studies. Nonetheless, the search for efficacious and tolerable efflux pump inhibitors continues because of the potential benefits. There is a need to consider efflux pump substrate selectivity in the design and development of novel chemotherapeutic agents.

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The effect of phenylalanine and glycine on chloramphenicol (CAP) induced bone marrow toxicity in albino rats infected with Klebsiella pneumoniae was investigated. The aim was investigate whether the treatment of the infected rats with either of these amino acids or their combination could reverse the major bone marrow toxicity of CAP. The study lasted for a period of 21 days in which haematological and histopathological changes were monitored in the infected rats. After 7 days, the rats became anaemic after treatment with CAP, but amino acids combined groups suppressed the anaemia and infection to some extent. At the end of 21 days, amino acids combination showed significant (p<0.05) suppression of anaemia except in CAP/Phenylalanine/glycine (group 4). Bone marrow examination showed the mechanism involved in the suppression of anaemia (amino acids administration triggered RBC compensatory mechanism seen as erythroid hyperplasia and myeloid hypoplasia). Histopathology changes ranges from hypocellularity in CAP group and fairly normocellularity in CAP/phenylalanine, CAP/glycine and necrotic/degenerative changes in group 4. Single amino acids combination with CAP have obvious protective effect and suppressed the bone marrow toxicity of CAP compared to the combination of the two amino acids with CAP , but all the combinations were effective in enhancing the efficacy of CAP.