Chlorhexidine effects

Green K, Livingston V, Bowman K. Chlorhexidine effects on corneal epithelium and endotheUum. Arch Ophthalmol 1980 98 1273-1278. 

Chlorhexidine is the most poteat oral antimicrobial agent available. It has side effects and is sold only with a prescription. It is active deflvered from a riase, but a compatible toothpaste vehicle for chlorhexidine has yet to be developed. 

After washing with chlorhexidine skin cleanser for 15 seconds, a 99.9% reduction of transient contaminants was achieved (216). Chlorhexidine is sometimes combined with alcohol to achieve the rapid reduction obtained with alcohol and the residual effect of chlorhexidine. It is substantive to the skin, and repeated use results in lower levels of bacteria on the skin. 

As is apparent from the above information, there is no ideal disinfectant, antiseptic or preservative. All chemical agents have their limitations either in terms of their antimicrobial activity, resistance to organic matter, stability, incompatibility, irritancy, toxicity or corrosivity. To overcome the limitations of an individual agent, formulations consisting of combinations of agents are available. For example, ethanol has been combined with chlorhexidine and iodine to produce more active preparations. The combination of chlorhexidine and cetrimide is also considered to improve activity. QACs and phenols have been combined with glutaraldehyde so that the same effect can be achieved with lower, less irritant concentrations of glutaraldehyde. Some... 

Quaternary ammonium compounds (QACs Chapter 10) such as cetrimide, and also the bisbiguanide, chlorhexidine, are notoriously prone to promote clumping. A non-ionic surface-active agent of the type formed by condensing ethylene oxide with a long-chain fatty acid such as Cirrasol ALN-WF (ICI Ltd), formerly known as Lubrol W, together with lecithin, added to the diluting fluid has been used to overcome this effect. 

In the weakly acidic preservatives, activity resides primarily in the unionized molecules and they only have significant efficacy at pHs where ionization is low. Thus, benzoic and sorbic acids (pKa = 4.2 and 4.75, respectively) have limited preservative usefulness above pH 5, while the 4(p)-hydroxybenzoate esters with their non-ionizable ester group and poorly ionizable hydroxyl substituent (pKa ca. 8.5) have moderate protective effect even at neutral pH levels. The activity of quaternary ammonium preservatives and chlorhexidine probably resides with their cations and are effective in products of neutral pH. Formulation pH can also directly influence the sensitivity of microorganisms to preservatives (see Chapter 11). 

Although this chapter is directed toward ophthalmic products, it is largely applicable to parenteral and even nonsterile products (solutions, emulsions, and suspensions). The choice of preservative is limited to only a few chemicals that have been found, over the years, to be safe and effective for this purpose. These are benzalkonium chloride, thimerosal, methyl- and propylparaben, phenylethanol, chlorhexidine,... 

Controlled and sustained drug delivery has recently begun to make an impression in the area of treatment of dental diseases. Many researchers have demonstrated that controlled delivery of antimicrobial agents, such as chlorhexidine [128-130], ofloxacin [131-133], and metronidazole [134], can effectively treat and prevent periodontitis. The incidence of dental caries and formation of plaque can also be reduced by controlled delivery of fluoride [135,136]. Delivery systems used are film-forming solutions [129,130], polymeric inserts [132], implants, and patches. Since dental disease is usually chronic, sustained release of therapeutic agents in the oral cavity would obviously be desirable. 

The most widely used and effective disinfectant solutions are based on iodine (iodophor) with concentrations ranging between 0.05% and 0.1%, but sometimes higher concentrations are recommended. Other agents such as chlorhexidine or chlorine dioxide, peroxide, sodium chloride and lactic acid may also be effective (Wilson et al., 1997) but are not common. Recent trials show positive effects of aloe vera-based dipping agents (Leon et al., 2004). One problem of iodine containing products is their low pH value (<4.0), which is necessary for their antimicrobial activity (Hansen and Hamann, 2003). 

Surface disinfectants Compounds containing phenolics, chlorhexidine (not effective against bacteria spores), quaternary ammonium salts (additional activity if bis-n-tributyltin oxide present), hypochlorites such as household bleach, alcohols such as 70-95% ethanol and isopropyl (not effective against bacteria spores), potassium peroxymonosulfate, hydrogen peroxide, iodine/iodophores, and triclosan. 

The most common bisphosphonate adverse effects are nausea, abdominal pain, and dyspepsia. Esophageal, gastric, or duodenal irritation, perforation, ulceration, or bleeding may occur when administration directions are not followed or when bisphosphonates are prescribed for patients with contraindications. The most common adverse effects of IV bisphosphonates include fever, flu-like symptoms, and local injection-site reactions. Osteonecrosis of the jaw occurs rarely if it develops, oral chlorhexidine washes, systemic antibiotics, and systemic analgesics are used based on severity. 

Camacho A, Gasparetto A, Svidzinski IE. (2007) The effect of chlorhexidine and gentian violet on the adherence of Candida spp. to urinary catheters. Mycopathologia 165 261-266. 

The rate of clearance of chlorhexidine from the mouth after one mouth rinse with 10 mL of a 0.2% aqueous solution follows approximately first-order kinetics, with a half-life of 60 minutes. This means that following application of a single rinse with a 0.2% chlorhexidine solution, the concentration of the compound exceeds the minimum inhibitory concentration (MIC) for oral streptococci (5 mg/mL) for almost 5 hours. The pronounced substantivity, along with the relative susceptibility of oral streptococci, may account for the great effectiveness of chlorhexidine in inhibiting supragingival plaque formation. 

The most conspicuous side effect of chlorhexidine is the development of a yellow to brownish extrinsic stain on the teeth and soft tissues of some patients. The discoloration on tooth surfaces is extremely tenacious, and a professional tooth cleaning using abrasives is necessary to remove it completely. The staining is dose dependent, and variation in severity is pronounced between individuals. This side effect is attributed to the cationic na-... 

As an oral rinsing agent, to date chlorhexidine has not been reported to produce any toxic systemic effects. Since chlorhexidine is poorly absorbed in the oral cavity and gastrointestinal tract, little if any enters the bloodstream. A summary of chlorhexidine oral rinses is given in Table 42.1. 

Chlorhexidine (C) is generally effective against all bacteria, but Streptococcus mutans and Actinomyces viscosus, two bacteria particularly associated with dental lesions, are especially susceptible to its action. Stannous fluoride (D) is widely used in caries prevention, and many studies have proven its effectiveness. 

Chlorhexidine is most effective against microorganisms in the solid form compared to a solution preparation. 

Yeasts (including Candida albicans) and dermatophytes are usually sensitive, although chlorhexidine fungicidal action is subject to species variation, as are other agents. The effective concentrations of chlorhexidine agents for bactericidal, bacteriostatic, sporicidal, and sporostatic organisms are listed in Table 2.13. 

Note 2 The standard disk diameter is 6 mm, an acceptable experimental value (zone of inhibition) is greater than the disc and can also be compared to chlorhexidine controls that are known to be effective antibacterial agents... 

Phenols Disrupt cell membranes, denature proteins, and inactivate enzymes phenol is not impaired by organic matter Phenol is used to disinfect surfaces and destroy cultures amylphenol destroys vegetative organisms and inactivates viruses on skin and objects chlorhexidine gluconate is effective as surgical scrub... 

Triclosan cannot only be applied as an emulsion, but it also has demonstrated antibacterial and antiinflammatory efficacy in eczema therapy when used as an antiseptic wash.28,30 Likewise, 10% povidone-iodine solution as a disinfectant showed excellent antibacterial activity together with improvement of clinical severity.79 As a 1% solution, chlorhexidine digluconate has shown superior effectiveness to triclosan in vitro, but may be only suitable for therapeutic use in intertriginous areas or as part of wet wrap dressings in the treatment of AD when used as an alcoholic solution.26,80... 

Rotter, M.L. et al., A comparison of the effects of preoperative whole-body bathing with detergent alone and with detergent containing chlorhexidine glucontate on the frequency of wound infections after clean surgery. J. Hosp. Infect. 11, 310-320, 1988. 

Stalder, J.F. et al., Comparative effects of two topical antiseptics (chlorhexidine vs. KMn04) on bacterial skin flora in atopic dermatitis. Acta Derm. Venereol. (Stockh.) 176(Suppl.), 132-134, 1992. 

---