Anti-fungals and Anti-Virals used in Ophthalmology

Pratyush Dhakal FO DOAOptometristAdvance Eye Hospital and InstituteSanpada,Navi Mumbai

Definition

• Antiviral drugs are a class of medication used specifically for treating viral infections.Like antibiotics for bacteria, specific antivirals are used for specific viruses. Unlike most antibiotics, antiviral drugs do not destroy their target pathogen; instead they inhibit their development.

ANTIVIRAL DRUGS• These are more often used locally in the eye.Currently available antiviral agents are

virostatic.• They are active against DNA viruses; especially herpes simplex virus. Antiviral drugs

used in ophthalmology can be grouped as below:• For herpes simplex virus infection• Idoxuridine• Vidarabine• Trifluridine• Acyclovir• Famiciclovir

For herpes zoster virus infection• Acyclovir• Famiciclovir• Valaciclovir• Vidarabine• Sorvudine

• For CMV retinitis• Ganciclovir• Foscarnet• Zidovudin• Non selective• Interferons• Immunoglobulins

• 1. Idoxuridine (IDU, 5-iodo-2 deoxyuridine). It is a halogenated pyrimidine resembling thymidine.

• Mechanism of action. It inhibits viral metabolism by substituting for thymidine in DNA synthesis and thus prevents replication of virus.Topically it is used as 10% eye drops.

• Preparations. It is available as 0.1 percent eye drops and 0.5 percent eye ointment.• Indications and doses: Since the intraocular penetration of topically applied IDU is

very poor, it is• not of much value in the treatment of chronic stromal herpetic keratitis. It is mainly

used in acute epithelial herpetic keratitis. IDU drops are used one hourly• during day and two hourly during night and has to be continued till microscopic

staining disappears.• Side-effects include follicular conjunctivitis, lacrimal punctal stenosis and irritation

with photophobia.• Contraindications. It is known to inhibit corneal stromal healing, hence its use is not

advisable during first few weeks after keratoplasty.

• Adenine arobinoside (Ara-A, Vidarabine). It is a purine nucleoside. It has antiviral activity against herpes simplex, cytomegalo, vaccinia and zoster viruses. It is more potent and less toxic than IDU andis also effective in IDU resistant cases. It has no cross allergenicity with IDU or TF3 and thus can be used with IDU.

• Mechanism of action: It is metabolized to triphosphate form which inhibits DNA polymerase and thus the growth of viral DNA is arrested.

• Preparations: It is available as 3% ophthalmic ointment.• Dose: It is used 5 times a day till epithelization occursand then

reduced to once or twice daily for 4-5 days to prevent recurrences. Side-effects are superificial punctate keratitis and irritation on prolonged application.

ANTIVIRAL DRUGS

3. Cytosine-Arabinoside (Cytarabine). It is a purine nucleoside, Mechanism of action: It blocks nucleicacid synthesis by preventing conversion of cytosineribose to cytosine deoxyribose.• Preparation: It is not commercially available at present. 5

percent solution used as drops has been found experimentally effective for treatment of herpes

simplex keratitis.• Side-effects. It causes profound corneal epithelial toxicity with

superficial punctate keratitis and iritis.• So it is not recommended for clinical use.

ANTIVIRAL DRUGS

• 3. Cytosine-Arabinoside (Cytarabine). It is a purinenucleoside, Mechanism of action: It blocks nucleic acid synthesis by preventing conversion of cytosine ribose to cytosine deoxyribose. Preparation: It is not commercially available at present. 5 percent solution used as drops has been found experimentally effective for treatment of herpes simplex keratitis. Side-effects. It causes profound corneal epithelial toxicity with superficial punctate keratitis and iritis. So it is not recommended for clinical use.

• 4. Triflurothymidine (TF3). It is a pyrimidine nucleoside. It has the advantage over IDU of higher solubility, greater potency, lack of toxicity and allergic reactions. It is also effective in IDU-resistant cases.

• Mechanism of action: It is a DNA inhibitor with same mechanism as IDU. Preparation: It is available as 1 per cent eyedrops.

• Dose: One drop is instilled 4 hourly. If no improvement occurs in 14 days, it is better to change to some other antiviral drug.

• Toxicity: It is least toxic. It may cause mild superficial punctate keratitis on prolonged use.

ANTIVIRAL DRUGS

Antiviral drugs• 5. Acyclovir (Acycloguanosine). It has proved to be an extremely safe and effective

agent and is effective n most forms of herpes simplex and herpes zoster infections. Mechanism of action: It inhibits viral DNA, preferentially entering the infected cells, with little effect on normal cells. It penetrates into deeper layers and thus is very effective in stromal keratitis.Preparation. It is available as 3 percent ophthalmic ointment and also as tablet for oral use and injection for intravenous use. Indications and doses: (a) Topical 3 percent ointment is used 5 times a day for epithelial as well as stromal herpes simplex keratitis (b) Oral acyclovir four tablets of 200 mg each, 5 times a day for 5-7 days, may be considered in following situations: (i) After penetrating keratoplasty in patients suffering from herpes simplex keratitis. (ii) Recalcitrant stromal or uveal disease caused by HSV. (iii) To reduce ocular complications of keratitis and uveitis in herpes zoster ophthalmicus. Side-effects: A few cases show slight punctate epithelial keratopathy which ceases once the drug is stopped.

• 6. Valaciclovir. It is used for treatment of herpes zoster ophthalmicus in a dose of 500-700 mg TDS for 7 days. It is as effective as acyclovir in acute disease and is more effective in reducing late neuralgia.

6. Valaciclovir. It is used for treatment of herpes zoster ophthalmicus in a dose of 500-700 mg TDS for 7 days. It is as effective as acyclovir in acute disease and is more effective in reducing late neuralgia.7. Famiciclovir. Its use, dose and effectivity is similar to valaciclovir.8. Interferons. These are non-toxic, species-specific proteins possessing broad-spectrum antiviral activity.However, it is still not available for commercial use. 9. Immunoglobulins. These preparations may be useful in the treatment or prophylaxis of certain viral diseases especially in patients with immune deficiencies.

Uses of Anti viral drugs

• Viral Conjunctivitis

• Herpetic keratitis

• Dendritic keratitis

• SPK’s

Anti-Fungal Drugs• A number of antifungal agents have become available in the recent years. These

can be broadly classified on the basis of their chemical structure into polyene antibiotics, imidazole derivatives, pyrimidines and silver compounds.

• I. Polyene antifungals These have been the mainstay of antifungal therapy. These are isolated from various species of Streptomyces and consist of a large, conjugated, double-bond system in a lactose ring linked to an amino acid sugar. Mechanism of action. They work by binding to the

• sterol groups in fungal cell membranes, rendering them permeable. This occurrence leads to lethal imbalances in cell contents. Polyenes do not penetrate

• well into the cornea and are not beneficial in dee stromal keratitis. Preparations. This group includes following drugs:

• 1. Nystatin. It is fungistatic and is well tolerated in the eye as 3.5 percent ointment. It has a medium level of activity in ocular infections caused by Candida or Aspergillus isolates. Because of its narrow spectrum and poor intraocular penetration its use is restricted.

• 2. Amphotericin B (Fungizone). This antibiotic may act as fungistatic or fungicidal depending upon the concentration of the drug and sensitivity of the fungus. Topically, it is effective in superficial infections of the eye in the concentration of 0.075 to 0.3 percent drops. Subconjunctival injections are quite painful and more than 300 mg is Poorly tolerated.

• Amphotericin B may be given intravitreally or/ and intravenously for treatment of intraocular infections caused by Candida, Histoplasma,Cryptococcus and some strains of Aspergillus and others. For intravenous administration a solution of 0.1 mg/ml in 5 percent dextrose with heparin is used.

• 3. Natamycin (Pimaricin). It is a broad-spectrum antifungal drug having activity against Candida,Aspergillus, Fusarium and Cephalosporium.Topical application of 5 percent pimaricin suspension produces effective concentrations within the corneal stroma but not in intraocular fluid. It is the drug of choice for fusarium solani keratitis. It adheres well to the surface of the ulcer, making the contact time of the antifungal agent with the eye greater. It is not recommended for injection.

• II. Imidazole antifungal drugs• Various imidazole derivatives available for use in ocular fungal infections include:

miconazole,clotrimazole, ketoconazole, econazole and itraconazole.• 1. Miconazole. It possesses a broad antifungal spectrum and is fungicidal to various species

of Candida, Aspergillus, Fusarium, Cryptococcus,Cladosporium, Trichophyton and many others.

• Topical (1%) and subconjunctival (10 mg)application of miconazole produces high levels of the drug in the cornea which is more dramatic in the presence of epithelial defect.• 2. Clotrimazole. It is fungistatic and is effective against Candida, Aspergillus and many

others. Its 1 percent suspension is effective topically and is the treatment of choice in Aspergillus infections of the eye.• 3. Econazole. It also has broad-spectrum antifungal activity and is used topically as 1

percent econazole nitrate ointment. Becaue of its poor intraocular penetration, it is effective only in superficial infections of the eye.

• 4. Ketoconazole. It is effective after oral administration and possesses activity against common fungi. It is given as single oral dose of 200-400 mg daily up to at least one week after the symptoms have disappeared. It is an adjunctive

systemic antifungal agent in fungal keratitis complicated by endophthalmitis.• 5. Fluconazole. It is fungistatic drug active against Candida, Aspergillus and Cryptococcus. It

is available for oral use (50-100 mg tablets) and also for topical use (0.2% eyedrops).• 6. Itraconazole. It is prescribed for treatment of fungal infections caused primarily by

Aspergillus,Histoplasmosis, Blastomycosis. It has moderate effect against Candida and Fusarium infections.

• It is available for oral and topical use. Oral dose is 200 mg twice daily for a week. Topically it is used as 1% eye drops.

• III. Pyridine• This group includes flucystosine, which is fluorinated salt of pyrimidine. Its mechanism of

action is not clear. The drug is very effective against Candida species and yeasts. It is used as 1.5 percent aqueous drops hourly. It can also be given orally or intravenously in doses of 200 mg/kg/day.

• IV. Silver compounds• Combination of silver with sulfonamides and with

other anti-microbial compounds significantly increases the activity against bacterial and fungal

• infections. In this context several silver compounds have been synthesized. Most frequently used is silver sulphadiazine which is reported to be highly effective against Aspergillus and Fusarium species.

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