EpistemisGanciclovir, Acyclovir
Ophthalmic antivirals specifically inhibit the synthesis of viral DNA in infected corneal cells, constituting the treatment of choice in acute epithelial herpetic keratitis.
Mechanism
💊 Commercial NamesVirgan, Zovirax Ophthalmic, Acyclovir Ophthalmic Ointment, Ganciclovir Ophthalmic Gel.
🔬 Pharmacological GroupAnalogs of purine and deoxyguanosine nucleosides. Specific antivirals.
Mechanism of Action
Acyclovir and ganciclovir act ultra-selectively on epithelial cells infected by herpesvirus:
- Selective Phosphorylation by Viral Thymidine Kinase: Once inside the ocular cell infected by Herpes Simplex Virus (HSV-1 or HSV-2) or Varicella-Zoster (VZV), the free drug is phosphorylated by the viral enzyme Thymidine Kinase (TK) to become acyclovir monophosphate or ganciclovir. This chemical reaction does not occur significantly in healthy cells, guaranteeing an excellent therapeutic index.
- Conversion to Active Triantagonists by Cellular Kinases: The cellular kinases of the host cell itself add two additional phosphate groups, generating the triphosphate form of the drug.
- Competitive Inhibition of Viral DNA Polymerase: Acyclovir/ganciclovir triphosphate competes with natural deoxyguanosine triphosphate (dGTP) for the active site of the viral DNA polymerase. When it is incorrectly incorporated into the nascent DNA chain of the virus, it causes obligated termination of the DNA chain (acyclovir lacks the 3' terminal hydroxyl group necessary to continue the phosphodiester bond), irreversibly stopping dural viral cell replication.
Pharmacokinetics
Quantitative Ocular and Systemic Pharmacokinetics
| Parameter | Ganciclovir Ophthalmic Gel 0.15% | Acyclovir Ophthalmic Ointment 3.0% |
|---|---|---|
| Formulation | Aqueous gel with hydrophilic carbomer polymer to optimize conjunctival contact. | Hydrophobic Vaseline greasy ointment with high local permanence. |
| Stromal Penetration | Good penetration into the anterior corneal stroma; less epitheliotoxicity. | Intermediate stromal penetration; requires an initial fatty thickness. |
| Tmax and Start | Tmax ≈ 1.5 - 2 h in basal corneal epithelium; Immediate start. | Tmax ≈ 2 hours average in cornea. |
| Retention and Elimination | Sustained release on the corneal epithelium; elimination by tears. | Prolonged persistence of the drug in the conjunctival fornix. |
| Plasma Bioavailability | Insignificant and below the detectable serum analytical limit. | Very low to no systemic absorption. |
The Dendritic Herpetic Ulcer against the Danger of Corticosteroids
Herpes Simplex Virus type 1 actively multiplies in the anterior corneal epithelium, inducing a typical cytopathic response characterized by keratocyte cell death and epithelial desquamation in the form of branches with terminal buttons called dendritic ulcers. The diagnosis is confirmed by topical fluorescein staining. If the clinician mistakenly prescribes topical corticosteroids without strict antiviral coverage, the local suppression of cellular immunity allows the virus to uncontrollably invade the deep stroma, transforming the dendrite into a giant geographic ulcer with corneal perforation and severe fibrovascular scarring of an irreversible course.
Security
Contraindications
- Absolute: Documented hypersensitivity to acyclovir, ganciclovir, valacyclovir or any of the excipients of the ophthalmic formulation.
- Relative: Concomitant use of therapeutic or cosmetic contact lenses due to interference in the diffusion of the active ingredient and adsorption of fatty excipients from the ointment.
Adverse Effects (ADR)
- Ocular Sites: Mild burning immediately after application; transient blurred vision due to viscosity of the ointment (acyclovir) or gel (ganciclovir); diffuse superficial punctate keratopathy; allergic contact blepharitis due to fatty accumulation on the eyelid margin.
- Systemic: Negligible due to no systemic absorption.
Epistemis is educational review material. It is not a medical device, does not diagnose or prescribe treatment, and does not replace formal medical training, current clinical guidelines, or professional clinical judgment.
- System
- Ophthalmology
- Cluster
- Chemotherapeutics Antivirals