Drugs in ophthalmology
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This document discusses antiviral and antifungal drugs used in ophthalmology. It defines antiviral drugs and outlines the life cycle of viruses in hosts. Several antiviral drugs are described for treating herpes simplex virus, herpes zoster virus, and CMV retinitis. Newer antiviral drugs like ganciclovir and foscarnet are also discussed. The document also covers various classes of antifungal drugs including polyenes, imidazoles, and pyridines. Specific drugs from these classes like natamycin, miconazole, fluconazole, itraconazole and voriconazole are described in detail for treating fungal infections.
Drugs in ophthalmology
- 1. Anti-Viral and Anti-fungal Drugs in Ophthalmology Speaker-Dr. Mamta Meena Dept of ophthalmology RNT Medical college, Udaipur
- 2. Definition • Antiviral drugs are a class of medication used specially 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.
- 3. 1. Adsorption 2. Entry 3. Uncoating 4. Transcription 5. Virus component synthesis Life cycle of virus in hosts
- 4. Life cycle
- 5. 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
- 6. For herpes zoster virus infection • Acyclovir • Famiciclovir • Valaciclovir • Vidarabine • Sorvudine
- 7. For CMV retinitis • Ganciclovir • Foscarnet • Zidovudin Non selective for viruses- • Interferons • Immunoglobulins
- 8. 1. Idoxuridine (IDU, 5-iodo-2 deoxyuridine). It is a halogenated pyrimidine resembling thymidine. Mechanism of action:- It inhibits viral DNA synthesis and thus prevents replication of virus. • Topically it is used as 10% eye drops. • Preparations- It is available as 0.1% eye drops and 0.5% eye ointment.
- 9. • 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.
- 10. • 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.
- 11. 1. Superficial Punctate Keratitis (SPK) 2. Indolent ulceration 3. Delayed epithelial healing 4. Stromal opacification 5. Chemosis 6. Hyperaemia 7. Follicles 8. Eyelid edema 8. Meibomian gland plugging 9. Punctal occlusion TOXICITY
- 12. 2. 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 and is 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 tri- phosphate form which inhibits DNA polymerase and thus the growth of viral DNA is arrested.
- 13. • Preparations: It is available as 3% ophthalmic ointment. • Dose: It is used 5 times a day till epithelization occurs and then reduced to once or twice daily for 4-5 days to prevent recurrences. • Side-effects are superficial punctate keratitis and irritation on prolonged application.
- 14. 3. Cytosine-Arabinoside (Cytarabine). It is a purine nucleoside. 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% 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.
- 15. 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.
- 16. • Preparation: It is available as 1% eye drops. • 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.
- 17. 1. Burning & Stingy sensation 2. Hyperaemia 3. Keratitis sicca 4. Delayed wound healing 5. Raised IOP Side Effects
- 18. 5. Acyclovir (Acycloguanosine). is a purine analog of guanosine. • It has proved to be an extremely safe and effective agent and is also effective in most forms of herpes simplex and herpes zoster infections. • Mechanism of action: It is converted to active tri-phosphate form by the viral and host cell enzyme, this active tri- phosphate form inhibits DNA synthesis and viral replication. • It penetrates into deeper layers and thus is very effective in stromal keratitis. • Preparation. It is available as 3% ophthalmic ointment and also as tablet for oral use and injection for intravenous use.
- 19. Doses of Acyclovir:- 1. Topical – 3% Ointment 2. Systemic – 1000mg/ 24 hr for 10 days 3. Intravenous- 5 mg/ kg 8 hrly for 5 – 10 days
- 20. Indications and doses of acyclovir- • (a) Topical 3% ointment is used 5 times a day for epithelial as well as stromal herpes simplex keratitis (b) Oral acyclovir 800 mg, 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.
- 21. 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.
- 22. 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.
- 23. (1) GANCICLOVIR- Ganciclovir is Guanine analogue and Structurally related to acyclovir INDICATIONS- 1. CMV Retinitis 2. Acute herpetic keratitis Contraindications- Hyperesensitivity to acyclovir or ganciclovir Some Newer anti-Viral drugs-
- 24. Doses of Ganciclovir- In CMV retinitis- (a) For Induction regime- 5mg/kg BD for 14-21 days f/b (b)Maintenance regime- 5 mg/kg IV OD daily for 5 out of 7 days.
- 25. • Ganciclovir ophthalmic 0.15% gel,(ZIRGAN)5 times a day until ulcer heals and then 3 times a day for 5 days. • It is more toxic than acyclovir. • It is a topical ophthalmic antiviral that is indicated for the treatment of acute herpetic keratitis.
- 26. • Most common adverse reactions reported in patients were blurred vision (60%), eye irritation (20%), punctate keratitis (5%), and conjunctival hyperemia (5%). • Safety and efficacy in paediatric patients below the age of 2 years have not been established.
- 27. • Foscarnet Inhibits viral DNA replication • Used in Acyclovir and Ganciclovir resistant infections. Doses of foscarnet in CMV Retinitis:- • Induction dose- 60 mg/Kg TDS for 2-3 weeks f/b • Maintenance dose:- 90 – 120 Mg/Kg OD daily (2) FOSCARNET
- 28. Anti-Fungal Drugs INTRODUCTION:- • Fungal infection is the raising prevalence in recently trends because of increased use of broad spectrum antibiotics, corticosteroids, anticancer, immunosuppressant drugs and emergence of AIDS. • As a result of breakdown of host defence mechanisms by the above agents, saprophytic fungi easily invade the living tissues. • A number of antifungal agents have become available in the recent years.
- 29. • These can be broadly classified on the basis of their chemical structure into A. polyene antibiotics, B. imidazole derivatives, C. pyrimidines and D. silver compounds.
- 30. (A) Polyene antifungals • is the 1st effective 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 (ergosterol) in fungal cell membranes, rendering them permeable followed by alters membrane permeability and disrupts the fungal cell, consecutive leads to lethal imbalances in cell contents.
- 31. • Polyenes do not penetrate well into the cornea and are not beneficial in deep stromal keratitis. • Use is restricted due to insolubility, irritation on application. • This group includes following drugs-
- 32. (1) Nystatin • 1st polyene antibiotic in 1950, derived from Streptomyces noursei. • It is fungistatic and is well tolerated in the eye as 3.5% 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.
- 33. (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% drops. • Sub-conjunctival injections are quite painful and more than 300 mg is Poorly tolerated.
- 34. • 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. • Total daily dosage may range up to 1.0 mg/kg per day or up to 1.5 mg/kg when given on alternate days.
- 35. 3. Natamycin (Pimaricin). • Natamycin derived from Streptomyces natalenses. • It is a broad-spectrum antifungal drug having activity against Candida,Aspergillus, Fusarium and Cephalosporium. • Topical application of 5% pimaricin suspension produces effective concentrations within the corneal stroma but not in intraocular fluid. • It is the drug of choice for fusarium solani keratitis.
- 36. • 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. • 5% topical suspension drops 4-6 times/day • Adverse reactions: irritation, burning, allergic reactions.
- 37. (B) 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%) instilled every hourly and subconjunctival (5-10 mg) every 48 hrs for 2-3 doses, application of miconazole produces high levels of the drug in the cornea which is more dramatic in the presence of epithelial defect.
- 38. (2) Clotrimazole • It is fungistatic and is effective against Candida, Aspergillus and many others. • Its 1% suspension is effective topically and is the treatment of choice in Aspergillus infections of the eye.
- 39. (3) Econazole. • It also has broad-spectrum antifungal activity and is used topically as 1% ointment and drops 4-6 times daily. • Because of its poor intraocular penetration, it is effective only in superficial infections of the eye.
- 40. (4) Ketoconazole. • It is effective after oral administration and possesses activity against common fungi But highly effective for treatment of keratomycosis. • It is an adjunctive systemic antifungal agent in fungal keratitis complicated by endophthalmitis.
- 41. • It is given as single oral dose of 200-400 mg daily up to at least one week after the symptoms have disappeared. • Topical 1-5% drops also used and well tolerated. • Reactions: relatively safe, but GIT upset, abnormal LFT, hypersensitivity and Reversible hepatotoxicity is occurs.
- 42. (5) Fluconazole. • 1st antifungal with good pharmacokinetic profile & relative low side effect • It is fungistatic drug active against Candida, Aspergillus and Cryptococcus. • It is used Orally, 200-600mg/day for 3 weeks for candida and 10-12 weeks in cryptococcus infection and also for topical use 0.2% eye drops every 4hrly.
- 43. (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 and Topically it is used as 1% eye drops.
- 44. (7) Voriconazole • Voriconazole is a new generation triazole antifungal agents, with broad-spectrum activity and high intraocular penetration. • Voriconazole eye drops have been used for the treatment of ophthalmic fungal keratitis. • The voriconazole eye drops used are of topically 1% concentration, well tolerated by the eye, and are stable..
- 45. • Have Good bioavailability and Good therapeutic concentrations • Completely inhibits ergosterol synthesis and more effective than fluconazole • Commonly used for invasive systemic and ocular infections specially aspergillosis and candidiasis • Oral dose of Voriconazole 200mg BD.
- 46. • S/E- Transient visual disturbances, fever, rash, vomiting, headache, abdominal pain. • Faster and deeper penetration • Highly effective in fungal keratitis with deep abscess • Outclasses all other antifungals.
- 47. (C) Pyridine • This group includes flucystosine, which is fluorinated salt of pyrimidine. MOA- After uptake into fungal cells, it is converted into 5-fluorouracil and then to 5-fluorodeoxyuridylic acid which is an inhibitor of thymidylate synthesis. Thymidylic acid is a component of DNA. • The drug is very effective against Candida species and yeasts. • It is used as 1.5% aqueous drops hourly. • It can also be given Orally 50-150mg/kg/day divided in 4 doses for a week.
- 48. (D) 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. • It is used to 1% drops hourly.
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