Keratitis, herpes

Amino-5-iodo-2, 5 -dideoxyuridine [56045-73-9] (13) C2H22IN2O4, was synthesized ia 1975 (27) and was found effective against herpes keratitis ia rabbits (28). This compound is markedly less cytotoxic than IdU, iadicating that it may have a safer and more specific mode of antiviral activity. A potential limitation of this group of nucleosides is their specificity, for they fail to inhibit all strains of herpes vimses. The specific antiviral activity of (13) is considered to be a result of the incorporation of the 5 -Ai-phosphate into both viral and host DNA in infected cells, but not into the DNA of normal cells. Phosphorylation of (13) occurs only in herpes vims-infected cells, brought about by a vims-induced thymidine kinase (29). 

Trifluridine, C2qH22F2N20, (5-trifluoromethyl-2 -deoxyuridine [70-00-8] F TdU, 14) was first prepared (30) in 1962. It is used for topical therapy of herpes vims-infected eyes. It is especially usefiil for treating infections that are resistant to IdU therapy. Like IdU, trifluridine is incorporated into DNA in place of thymidine in both infected and uninfected cells. But it is 10 times more potent than IdU against herpes keratitis in rabbits and 10 times more soluble in water. Trifluridine is also usefiil in treating human cytomegalovims (HCMV), but its toxicity to bone marrow may limit its clinical use. 

Oral acyclovir is useful in the treatment of HSV-1 and HSV-2 infections, such as genital herpes, herpes encephalitis, herpes keratitis, herpes labialis, and neonatal herpes. In initial episodes of genital herpes, oral acyclovir has been found to reduce viral shedding, increase the speed of healing of lesions, and decrease the duration of pain and new lesion formation. Acyclovir appears to be less effective in the treatment of recurrent herpes genitalis but may be used for the long-term suppression of recurrent HSV. 

Trifluridine Topical Herpes keratitis 1 drop 9 times daily for 7 days... 

Recent work has centered upon use of interferon as a therapeutic agent in humans and animals. In humans, local application of monkey interferon is effective in reducing the seventy of vaccinia virus skin infections. Recent results with herpes keratitis and chronic hepatitis are promising. Interferon appears to be active against oncogenic viruses in the treatment of such cancers as osteogenic sarcoma, and at present it is only the limited availability of interferon that pie vents more extensive testing. 

Research in antiviral chemotherapy began in the early 1950s, when the search for anticancer drugs generated several new compounds capable of inhibiting viral DNA synthesis. The two first-generation antivirals, 5-iododeoxyuridine and trifluorothymidine, had poor specificity (ie, they inhibited host cellular as well as viral DNA) that rendered them too toxic for systemic use. However, both are effective when used topically for the treatment of herpes keratitis. 

The 5-chloro, 5-bromo and 5-iodo derivatives of uracil are base analogues of thymine and, in cellular systems, can replace the latter in DNA u >. Furthermore, 5-iodo-2 -deoxyuridine is an antiherpes agent currently used for treatment of ocular herpes keratitis. By contrast, 5-fluorouracil can replace uracil in RNA, and, together with 5-fluoro-2 -deoxyuridine, is employed in tumour chemotherapy. All the foregoing are also known mutagens, and 5-bromouracil and its deoxyriboside are widely employed in studies on mutagenesis U9). 

Polcicova K. Herpes keratitis in the absence of anterograde transport of virus for sensory gangUa to the cornea. Proc Natl Acad Sci USA 2005 102(32) 11462-11467. 

Herpes keratitis (see p. 258). It is essential that a corticosteroid should never be put on the eye the disease is exacerbated and permanent blindness can result. 

A 59-year-old woman on hemodialysis was treated with oral aciclovir 200 mg/day for ophthalmic Herpes zoster. After a few days, an ophthalmic aciclovir cream was started (one application every 6 hours) because of ipsi-lateral Herpes keratitis. After 1 week of combined oral and topical treatment, she became confused, with dysarthria and audiovisual hallucinations. Aciclovir was withdrawn and hemodialysis was initiated. Complete resolution of symptoms was achieved after three hemodialysis sessions in 3 days. Aciclovir plasma concentrations before hemodialysis were high (45 pmol/l) and fell rapidly during hemodialysis. 

Vidarabine Vidarabine is an adenine analog and has activity against HSV, VZV, and CMV. Its use for systemic infections is limited by rapid metabolic inactivation and by marked toxic potential. However, it has been used intravenously for severe HSV infections, including those resistant to acyclovir, and it also prevents the dissemination of varicella-zoster virus in immunocompromised patients. Vidarabine is used topically for herpes keratitis, but it has no effect on genital lesions. Toxic effects with systemic use include gastrointestinal irritation, paresthesias, tremor, convulsions, and hepatic dysfunction. Vidarabine is teratogenic in animals. 

Idoxuridine and tiifluridine These pyrimidine analogs are used topically in herpes keratitis. They are too toxic for systemic use. 

Results in ocular herpes keratitis are usually more positive and there is no doubt of the value of the drug in this form of infection [191, 192]. Some patients have been found to be resistant to treatment but in only 2 out of 12 such patients in one trial was the isolated virus found to be actually more drug-resistant than the normal wild-type virus. In this paper [192] the value of IDUR in herpes keratitis of man was critically assessed from the information available in mid-1969. 

A comparison of 1-p-D-arabinofuranosylcytosine and 1-P-D-arabinofuranosyl-5-fluorocytosine as inhibitors of herpes keratitis infection in rabbits and of vaccinia in tissue culture indicated comparable activity. The compound,... 

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