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Chapter 27 : Effects on Connective Tissue Structures

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Abstract:

Quinolones have the potential to damage cartilage as well as tendons, thus being able to cause unusual forms of adverse drug reactions. Less is known about the effects on the epiphyseal growth plate, tendons, and other connective tissue structures, than about quinolone-induced lesions of the immature articular cartilage in animals. The current knowledge about the various target tissues is summarized in this chapter, but first, some brief general remarks about pharmacokinetics in experimental animals and humans and about the hypothetical mechanism of the toxic effects on connective tissue structures are given. The exact mechanism of quinolone-induced arthropathy or tendopathy is still unknown. Effects on the epiphyseal growth plate have also been reported after treatment with moxifloxacin in immature dogs. When beagles aged 10 to 12 weeks were treated with moxifloxacin, degeneration of the matrix as well as the chondrocytes was observed in the epiphyseal growth plates; however, no such effects were found in 18 to 22-week-old dogs under otherwise identical conditions. Results were similar for the ciprofloxacin treated dogs as well as the magnesium-deficient dogs. These findings support our hypothesis that quinolone-induced toxic effects on connective tissue structures are caused by the magnesium-antagonistic effects of these antibacterial agents. In summary, human experience with ciprofloxacin seems to indicate that no or minimal risks for quinolone-induced arthropathy exist. Another toxic reaction of a connective tissue structure is tendinopathy. The main sources of information are case reports, compilations from administrative authorities, or isolated retrospective studies that cover only the older compounds.

Citation: Stahlmann R. 2003. Effects on Connective Tissue Structures, p 441-449. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch27
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Figure 1

Tenocytes from rat achilles tendons. (A) Rat was treated orally with the vehicle from day 32 to day 36 postnatally. (B) Rat was treated orally with 600 mg ciprofloxacin/kg of body weight from day 32 to day 36 postnatally. In comparison with the controls, cellular as well as matrix alterations are detectable by electron microscopy in tendon samples from quinolone-treated rats. Note the vacuoles and large vesicles in the cytoplasm of tenocytes (arrows) resulting from swellings and dilatations of cell organelles (mitochondria, endoplasmic reticulum). Cells are detached from the matrix, and the fibril diameter is decreased in the ciprofloxacin-treated rats. Similar changes were observed in Achilles tendons after treatment with ofloxacin or garenoxacin. Reprinted from reference 33a with permission.

Citation: Stahlmann R. 2003. Effects on Connective Tissue Structures, p 441-449. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch27
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References

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Tables

Generic image for table
Table 1

Toxic effects of quinolones on connective tissue structures

Citation: Stahlmann R. 2003. Effects on Connective Tissue Structures, p 441-449. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch27
Generic image for table
Table 2

Risk for Achilles tendinitis by fluoroquinolones compared with other antibacterial agents

Citation: Stahlmann R. 2003. Effects on Connective Tissue Structures, p 441-449. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch27

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