Dental Dictionary:
vidarabine |
n
(ophthalmic), trade name: Vira-A Ophthalmic; class: antiviral; action: inhibits DNA synthesis by blocking DNA polymerase; use: keratoconjunctivitis due to herpes simplex virus.
Page Contents
vidarabine
n
| Drug Info: Vidarabine |
Brand names: Vira-A®
- Español:
- Pomada ocular de vidarabina
Vidarabine eye ointment
What is vidarabine eye ointment?
VIDARABINE (Vira-A®) is an antiviral agent. As an eye ointment it is effective in the treatment of herpes eye infections. Generic vidarabine eye ointment is not available.What should I tell my health care provider before I take this medicine?
They need to know if you have any of these conditions:• an unusual or allergic reaction to vidarabine, other medicines, foods, dyes, or preservatives
• pregnant or trying to get pregnant
• breast-feeding
How should I use this medicine?
Vidarabine eye ointment is only for use in the eye. Do not take by mouth. Follow the directions on the prescription label. Wash hands before and after use. Tilt your head back slightly and pull your lower eyelid down with your index finger to form a pouch. Try not to touch the tip of the tube, to your eye, fingertips, or any other surface. Squeeze the end of the tube to apply a thin layer of the ointment to the inside of the lower eyelid. Close the eye gently to spread the ointment. Your vision may blur for a few minutes. Use your doses at regular intervals. Do not use your medicine more often than directed. Finish the full course prescribed by your prescriber or health care professional even if you think your condition is better.Contact your pediatrician or health care professional regarding the use of this medicine in children. Special care may be needed.
What if I miss a dose?
If you miss a dose, use it as soon as you can. If it is almost time for your next dose, use only that dose. Do not use double or extra doses.What drug(s) may interact with vidarabine?
• corticosteroid eye ointments (such as prednisolone, dexamethasone)Do not use any other eye products without telling your prescriber or health care professional. Check before starting or stopping any of your medicines or non-prescription products.
What should I watch for while taking vidarabine?
Tell your prescriber or health care professional if your symptoms worsen or do not improve within a few days. Visit your prescriber or health care professional for regular checks on your progress. This medicine is not intended for long-term use because it can cause permanent damage to the cornea (the front of the eye). Do not use for more than 3 weeks.Wear sunglasses if eyes become sensitive to light.
What side effects may I notice from using vidarabine?
Side effects that you should report to your prescriber or health care professional as soon as possible:• burning, stinging, or itching of the eyes or eyelids
• eye pain
• increased sensitivity of the eyes to light
• swollen eyelids
Side effects that usually do not require medical attention (report to your prescriber or health care professional if they continue or are bothersome):
• excess of tears
• feeling as if there is something in the eye
Where can I keep my medicine?
Keep out of the reach of children.Store at room temperature between 15 and 30 degrees C (59 and 86 degrees F). Do not freeze. Throw away any unused medicine after the expiration date.
Last updated: 7/1/2002
Important Disclaimer: The drug information provided here is for educational purposes only. It is intended to supplement, not substitute for, the diagnosis, treatment and advice of a medical professional. This drug information does not cover all possible uses, precautions, side effects and interactions. It should not be construed to indicate that this or any drug is safe for you. Consult your medical professional for guidance before using any prescription or over the counter drugs.
| Medical Dictionary: vi·dar·a·bine |
n.
A purine nucleoside obtained from a species of Streptomyces and used in the treatment of herpes simplex infections.
| Veterinary Dictionary: vidarabine |
A purine analog, adenine arabinoside (ara-A), that inhibits DNA synthesis; used as an antiviral agent to treat herpesvirus infection.
| Wikipedia: vidarabine |
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Vidarabine
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| Systematic (IUPAC) name | |
| 2-(6-aminopurin-9-yl)- 5-(hydroxymethyl) oxolane-3,4-diol hydrate | |
| Identifiers | |
| CAS number | |
| ATC code | J05 S01AD06 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C10H15N5O5 |
| Mol. mass | 285.257 g/mol |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Protein binding | 24-38% |
| Metabolism | ? |
| Half life | ? |
| Excretion | ? |
| Therapeutic considerations | |
| Pregnancy cat. |
? |
| Legal status | |
| Routes | ? |
Vidarabine is an anti-viral drug which is active against herpes simplex and varicella zoster viruses.
How the drug was discovered
In the 1950’s two nucleosides were isolated from the Caribbean sponge Tethya crypta: spongothymidine and spongouridine; which contained an arabinoside sugar rather than a ribose. These compounds led to the synthesis of a new generation, sugar modified nucleoside analog: vidarabine, and the related compound: cytarabine. In 2004 these were the only marine related compounds in clinical use.[1] The anti-viral activity of vidarabine was first described by M. Privat de Garilhe and J. De Rudder in 1964.[2] It was the first nucleoside analog antiviral to be given systemically and was the first agent to be licensed for the treatment of systematic herpes virus infection in man.[3] It was Dr. Richard Whitley in 1976 where the clinical effectiveness of vidarabine was first realised, and vidarabine was used in the treatment of many viral diseases.[2]
Vidarabine (9-β-D-ribofuranosyladenine) is an analog of adenosine with the D-ribose sugar, replaced with D-arabinose. As you can see from figure 1.1 that it is a stereoisomer of adenosine. It has a half life of 60 minutes, and its solubility is 0.05%, and is able to cross the blood-brain barrier (BBB) when converted to its active metabolite.[4]
Mode of Action
The Mechanism of Action of Vidarabine
Vidarabine works by interfering with the synthesis of viral DNA.[5] It is a nucleoside analog and therefore has to be phosphorylated to be active. This is a three step process in which vidarabine is sequentially phosphorylated by kinases to the triphosphate ara-ATP. This is the active form of vidarabine and is both an inhibitor and a substrate of viral DNA polymerase.[6] When used as a substrate for viral DNA polymerase, ara-ATP competitively inhibits dATP leading to the formation of ‘faulty’ DNA. This is where ara-ATP is incorporated into the DNA strand replacing many of the adenosine bases. This results in the prevention of DNA synthesis, as phosphodiester bridges can longer to be built, destabilizing the strand. Vidarabine triphosphate (ara-ATP) also inhibits RNA polyadenylation; preventing polyadenylation essential for HIV-1 and other retroviruses; and S-adenosylhomocysteine hydrolase, preventing transmethylation reactions. Uniquely to vidarabine, the diphosphorylated vidarabine (ara-ADP) also has an inhibitory effect. Other nucleoside analogs need to be triphosphorlated to give any antiviral effect, but ara-ADP inhibits the enzyme ribonucleotide reductase. This prevents the reduction of nucleotide diphosphates, causing a reduction of viral replication.[6]
Mode of Resistance
Vidarabine is more toxic and less metabolically stable than many of the other current antivirals such as acyclovir and ganciclovir. Viral strains resistant to vidarabine show changes in DNA polymerase. It is prone to deamination by adenosine deaminase to a hypoxanthine.[7] This metabolite still possesses antiviral activity, but is 10-fold less potent than vidarabine.[8] 60% of vidarabine eliminated by the kidney is excreted as arabinosyle-hypoxanthine in the urine. Some breakdown of the purine ring may also occur, forming uric acid.[9] Structural modifications of vidarabine have proven partially effective at blocking deamination, such as replacement of the amine with a methoxy group (ara-M). This results in about a 10-fold greater selectivity against Varicella Zoster Virus than ara-A, however analog of vidarabine is inactive against other viruses due to it not being able to be phosphorylated.[8] The use of an inhibitor of adenosine deaminase to increase the half life of vidarabine has also been tried, and drugs such as dCF and EHNA have been used with a small amount of success.
Synthesis/preparation/isolation
Vidarabine has been synthesised using E. coli bacterial cells,[10] and by using Vorbrüggen glycosylation with a Lewis acid catalyst. This involves the reaction of a base with a sugar and is used to synthesise natural ßβ-nucleosides.[11]
Selectivity
Vidarabine is less susceptible to the development of drug resistant strains than other antivirals such as IDU, and has been used successfully in the treatment of IDU resistant viral strains. The half life of the active triphosphate metabolite (ara-ATP) is three times longer in HSV-infected cells compared with uninfected cells,[8] however the mechanism of selectivity is not known.
Current clinical Indication
Vidarabine is an antiviral, active against herpes viruses, poxviruses, rhabdoviruses, hepadnarviruses and some
RNA tumour viruses. A 3% ophthalmic ointment Vira-A is used in the treatment of acute
keratoconjuctivitis and recurrent superficial keratitis caused by HSV-1 and HSV-2.[12] Vidarabine is also used to treat herpes zoster in AIDS patients,
reducing lesions formation and the duration of viral shedding. Many of the previous uses of vidarabine have been superseded by
acyclovir, due to the hospitalisation required for intra venous dosing, and acyclovir has a
higher selectivity, lower inhibitory concentration and higher potency. Toxic side effects are rare, but have been reported with
high concentrations of vidarabine, such as nausea, vomiting, leukopenia and
References
- ^ Kijjoa, A.; Sawangwong, P. Drugs and Cosmetics from the Sea. Mar. Drugs. 2004, 2, 73-82.
- ^ a b Field, H. J.; De Clercq, E. Antiviral Drugs – a short history of their discovery and development. Microbiology Today. 2004, 31, 58-61.
- ^ White, O. D.; Fenner, F. J. Medicinal Virology. 3rd Ed.
- ^ Waterson, A. P. Recent Advances in Clinical Virology (2).
- ^ Merck Manual. 17th Ed. Chapter 154, p.1127-1128.
- ^ a b McGuigan, C. Antiviral Chemotherapy – Cardiff University, 3rd Year Pharmacy Notes Lecture Notes.
- ^ Whitley, R. J.; Tucker, B. C.; Kinkel, A. W.; Barton, N. H.; Pass, R. F.; Whelchel, J. D.; Cobbs, C. G.; Diethelm, A. G.; Buchanan, R. A. Pharmacology, Tolerance, and Antiviral Activity of Vidarabine Monophosphate In Humans.
- ^ a b c Burgers Medicinal Chemistry and Drug Discovery. 6th Ed.
- ^ BIAM - L'Ecole Nationale Supérieure des Mines de Paris http://www.biam2.org//www/Sub1767.html#SubIndic.
- ^ Roshevskaia, L. A.; Barai, V. N.; Zinchenko, A. I.; Kvasiuk, E. I.; Mikhailopulo, L. A. Preparative synthesis of the antiviral nucleoside 9-beta-D-arabinofuranosyladenine by using bacterial cells. Antibiot. Med. Biotekhnol. 1986, 31(3), 174-8.
- ^ Wang, Z.; Prud'homme, D. R.; Buck, J. R.; Park, M.; Rizzo, C. J. Stereocontrolled syntheses of deoxyribonucleosides via photoinduced electron-transfer deoxygenation of benzoyl-protected ribo- and arabinonucleosides. J Org Chem. 2000, 65(19), 5969-85.
- ^ Drug Information Online - http://www.drugs.com/MMX/Vidarabine.html
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