The mechanism of action of idoxuridine has not been completely defined, but several steps are involved in the activation of the drug. Idoxuridine enters the cell and is phosphorylated at O-5 by a viral thymidylate kinase to yield a monophosphate, which undergoes further biotransformation to a triphosphate. The triphosphate is believed to be both a substrate and an inhibitor of viral DNA poly-merase, causing inhibition of viral DNA synthesis and facilitating the synthesis of DNA that contains the iodinated pyrimidine. The altered DNA is more susceptible to strand breakage and leads to faulty transcription. When the iodin-ated DNA is transcribed, the results are miscoding errors in RNA and faulty protein synthesis. The ability of idox-uridylic acid to substitute for deoxythymidylic acid in the synthesis of DNA may be a result of the similar van der Waals radii of iodine (2.15 A) and the thymidine methyl group (2.00 A).
In the United States, idoxuridine is approved only for the topical treatment of herpes simplex virus (HSV) keratitis;
although outside the United States, a solution of idoxuridine in dimethyl sulfoxide is available for the treatment of herpes labialis, genitalis, and zoster. The use of idoxuridine is limited because the drug lacks selectivity; low, subtherapeutic concentrations inhibit the growth of uninfected host cells. The effective concentration of idoxuridine is at least 10 times greater than that of acyclovir.
Idoxuridine occurs as a pale yellow, crystalline solid that is soluble in water and alcohol but poorly soluble in most organic solvents. The compound is a weak acid, with a pKa of 8.25. Aqueous solutions are slightly acidic, yielding a pH of about 6.0. Idoxuridine is light and heat sensitive. It is supplied as a 0.1% ophthalmic solution and a 0.5% ophthalmic ointment.
Cytarabine is a pyrimidine nucleoside drug that is related to idoxuridine. This agent is primarily used as an anticancer agent for Burkitt lymphoma and myeloid and lymphatic leukemias. Cytarabine blocks the cellular utilization of de-oxycytidine, hence inhibiting the replication of viral DNA. Before it becomes active, the drug is converted to monophosphates, diphosphates, and triphosphates, which block DNA polymerase and the C-2 reductase that converts cytidine diphosphate into the deoxy derivative.
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Hypnosis has been defined as a state of heightened suggestibility in which the subject is able to uncritically accept ideas for self-improvement and act on them appropriately. When a hypnotist hypnotizes his subject, it is known as hetero-hypnosis. When an individual puts himself into a state of hypnosis, it is known as self-hypnosis.