Antimicrobials, toxic effects

It has been observed that quite generally the toxic effects of organometallic compounds are stronger than those of the underlying metal ions. This is particularly true for the antimicrobial effects. The metal tin shows this phenomenon in a rather dramatic way. Whereas scarcely any pronounced biological effect is known for tin, either in the stannous or the stannic form, certain trialkyltin compounds belong to the most active fungicides known at present. 

Radiosensitizing effect in hypoxic cells [84, 91, 123—126], in normal tissue [123] toxicity to hypoxic cells [112, 113, 115, 116, 124, 125, 127], toxicity in vivo [128] antimicrobial drugs (effect on single- or double-stranded DNA Escherichia coli) [112] antiprotozoan, antibacterial (Salmonella typhimurium cells [123] and antitrichomonal activity [128, 129]) inhibition of ribonucleotide-reductase [130] structure—activity [115, 116, 127]... 

The quaternary surfactants benzalkonium chloride (BAG) and benzethonium chloride are preferred by many manu-fecturers because of their stabihty, excellent antimicrobial properties in acid formulation, and long shelf life. They exhibit toxic effects on both the tear film and the corneal epithelium and have long been known to increase drug penetration. The toxicity of these compounds may be increased by the degree of acidity of the formulation. 

Both in vitro and in vivo studies of corneal epithelial cells have demonstrated the potential for toxicity to BAC. The implication is that chronic use of BAC-containing glaucoma medications has the potential to cause or exacerbate ocular surfece disease.This research has led to the development of a BAC-free prostaglandin analogue for the treatment of glaucoma. Travoprost (Travatan Z) is formulated with a imique ionic buffered compound consisting of zinc, sorbitol, and borate (sofZia), which has the preservative and antimicrobial properties of BAC but without its associated toxic effects. 

Klebanoff SJ and Shepard CC Toxic Effect of the Peroxidase-hydrogen peroxide-halide Antimicrobial System on Mycobacterium leprae. Infect. Immun. 1984 44(2) 534-6. 

Aside from consideration of drug toxicity, some antimicrobial use requires more in tensive risk-benefit analysis. An example of this is the decision to use isoniazid prophylactically to prevent tuberculosis. Because the hepatotoxicity of isoniazid increases in frequency with age, older persons (>45 years) who are candidates for isoniazid prophylaxis (positive skin test) must have additional risk factors for tuberculosis to balance the potential toxic effects. These include evidence of recent skin-test conversion, immunosuppression, or previous gastrectomy. Older patients without additional risk factors are more likely to suffer toxicity from isoniazid than derive benefit from its use. ... 

Selective toxicity is the ability of an antimicrobial agent to act on an infecting organism without toxic effects on host cells. The extent of selective toxicity depends on its mechanisms of action, of which there are five basic categories, as shown in Table V-l-1. 

The antimicrobial effects of licorice may extend beyond antiviral activity. Licochalcone A, a flavonoid component of licorice found in alcoholic root extracts, has been found to inhibit the growth of Leishmania major and Leishmania donovani promastigotes and amastigotes in vitro (Chen et al., 1993). Licochalcone A appears to elicit its toxic effects upon the protozoal mitochondria in concentrations that do not harm human leukocytes. 

The physiological importance of NO is due to both its regulatory and its toxic functions. NO produced in a regulated manner serves to control a multitude of cellular reactions. However, excessive production of NO can have toxic effects and is also used in mammals for antimicrobial action (review Hausladen and Stamler, 1999 Toreilles, 2001, Stamler et al., 2001). 

All ophthalmic medications are potentially absorbed into the systemic circulation (Figure 63-3), so undesirable systemic side effects may occur, as well as potential local toxic effects due to hypersensitivity reactions or to direct toxic effects on the cornea, conjunctiva, periocular skin, and nasal mucosa. Eyedrops and contact lens solutions commonly contain preservatives such as ben-zalkonium chloride, chlorobutanol, and chelating agents for their antimicrobial effectiveness. In particular, benzalkonium chloride may cause a punctate keratopathy or toxic ulcerative keratopathy. 

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