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Chapter: Modern Pharmacology with Clinical Applications: Antiviral Drugs

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Antiherpesvirus Agents: Vidarabine

Vidarabine (adenine arabinoside, Vira-A) is an adenine nucleoside analogue containing arabinose in place of ribose.

Vidarabine

 

Vidarabine (adenine arabinoside, Vira-A) is an adenine nucleoside analogue containing arabinose in place of ri-bose. It is obtained from cultures of Streptomyces an-tibioticus and has activity against HSV-1, HSV-2, VZV, CMV, HBV, poxviruses, hepadnaviruses, rhabdoviruses, and certain RNA tumor viruses.

 

Vidarabine’s specific mechanism of action is not fully understood. Cellular enzymes convert this drug to a triphosphate that inhibits DNA polymerase activity. Vidarabine triphosphate competes with deoxyadeno-sine triphosphate (dATP) for access to DNA poly-merase and also acts as a chain terminator. Although vidarabine is incorporated into host DNA to some ex-tent, viral DNA polymerase is much more susceptible to inhibition by vidarabine. Vidarabine also inhibits ri-bonucleoside reductase and other enzymes. Resistance occurs as a result of DNA polymerase mutation.

 

Absorption, Metabolism, and Excretion

 

Vidarabine is administered only as a topical ophthalmic ointment. It has relatively limited solubility and is not significantly absorbed after application to the eye. Within the tissues, it is rapidly deaminated to its princi-pal metabolite, arabinosyl hypoxanthine, which retains some degree of antiviral activity.

 

Clinical Uses

 

The principal use of vidarabine is in the treatment of HSV keratoconjunctivitis. It is also used to treat super-ficial keratitis in patients unresponsive or hypersensi-tive to topical idoxuridine.

 

Adverse Effects, Contraindications, and Drug Interactions

 

The most commonly observed side effects associated with vidarabine are lacrimation, burning, irritation, pain, and photophobia. Vidarabine has oncogenic and mutagenic potential; however, the risk of systemic ef-fects is low because of its limited absorption. It should not be used in conjunction with ophthalmic cortico-steroids, since these drugs increase the spread of HSV infection and may produce side effects such as in-creased intraocular pressure, glaucoma, and cataracts.

 

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