Structural Development, Haematological Immunological and Pharmacological Effects of Quinolones

Abstract

The interest of the medical community in quinolones has not decreased despite more than ten years of continuous and growing use of these agents. The constant need for new anti microbials has produced a variety of newer quinolones termed as I, II, III, and IV generation. Nalidixic acid and other early quinolones had limited use due to poor pharmacokinetics, relatively narrow antimicrobial spectrum of activity, and frequent adverse effects. Extensive pharmacologic and clinical development of quinolone antimicrobial agents has resulted in improved antimicrobial activity, pharmacokinetic features, toxicity, and drug-drug interaction profiles. These attributes, coupled with their expanded spectrum and the immune enhancing phenomena of quinolones with a cyclopropyl moiety at position 1 of the quinolone ring suggest that the newer fluoroquinolones are so far the most ideal agents for the empirical treatment of many common infections. The above has made it desirable to review the status of these agents as revealed in published literature. The thrust of this review is on the structural development, pharmacological, haematological and immunological effects of quinolones. Recent patents filed are also discussed.

Cellular and humoral immunodepression in vultures feeding upon medicated livestock carrion

“…Many potential action mechanisms may be simultaneously involved in immunodepression due to antibiotic ingestion (Levy 2002;Chide & Orisakwe 2007), as indicated by the fact that both cellular and humoral systems were affected to variable degrees by the presence of circulating antibiotics. The complex inter-relationships between cellular and humoral immunities may explain the patterns of variation of the different immunological parameters due to chronic but discontinuous or recent ingestion of antibiotics.…”

“…The recently proposed phage antibiotic synergy hypothesis suggests a massive deleterious growth of bacteriophages due to quinolone application (Comeau et al 2007). Therefore, the potentially detrimental impact of antibiotics on the immune system, generally associated with their misuse, may be complex as several very different action mechanisms, immunological subsystems and metabolic routes may be involved (Levy 2002;Chide & Orisakwe 2007). All of these negative effects of antibiotics may be exacerbated in developing animals because of their partial dependence on passive maternal immunity, active development of immune organs and, hence, limited functional activity of their immune system (Tizard 2000;Fellah et al 2008).…”

“…Previously, a clear association between quinolone ingestion, pathogen acquisition and mortality has been found in vultures (Lemus et al 2008). However, there are no data regarding how antibiotics may negatively affect vulture health, although it has been suggested that the effects are partially due to the immunodepressive impact of antibiotics under conditions of chronic but discontinuous ingestion (Lemus et al 2008), similar to the effects derived from misuse of these drugs in humans (Levy 2002;Chide & Orisakwe 2007). In fact, the immunodepressive effects of antibiotics have long been established ( Norrby & Lietman 1993;Brown 1996;Walker 2000;Lathers 2002), especially in continued treatments, causing fungal overgrowth in place of protective normal bacterial flora due to their selective elimination, as well as direct effects on normal production and activity of lymphocytes (Levy 2002;Chide & Orisakwe 2007).…”

“…Antibiotics are administered only when an individual is not able to eliminate an infection. If antibiotics are ingested under inappropriate conditions in terms of concentration, timing and duration of treatment, the active molecules can cause primary suppression of lymphocyte proliferation and bone marrow ( Jiménez-Valera et al 1995;Chide & Orisakwe 2007). Other detrimental effects include the blocking of the specific target molecules for macrophage activity, impeding their proper function (Azuma et al 2001).…”

The simple synthesis and antimicrobial activity of novel fluoroquinolone derivatives from natural amino acid salts

“…(Silva et al, 2003;Chide and Orisakwe 2007;Chen et al, 2001;Miyauchi et al, 2009). Due to such a wide range of applicability in medicine, bioorganic chemistry, as well as synthetic organic chemistry, there has been increasing interests in the development of new quinolone and fluoroquinolone derivatives to enrich this domain (Sakineh et al, 2009;Murugesan et al, 2008;Chai et al, 2009).…”