EpistemisNatamycin, Amphotericin B
Fungal keratitis constitutes an ophthalmological emergency that directly threatens the integrity of the eye. The use of topical polyenes such as natamycin and amphotericin B is required to destroy the fungal membranes of yeasts and filamentous fungi.
Mechanism
💊 Commercial NamesNatacyn, Amphotericin B Master Formulas, Natamycin Eye Drops 5%.
🔬 Pharmacological GroupAntifungal polyene macrolides with direct membrane action. Topical chemotherapy drugs.
Mechanism of Action
Natamycin and amphotericin B act by altering the stability of the cell membrane of pathogenic fungi:
- Direct Binding to Membrane Ergosterol: They bind with extreme selectivity and high affinity to ergosterol, the fundamental and constitutive lipid of the fungal membrane bilayer, absent in human cells (where cholesterol predominates).
- Transmembrane Pore Formation (Amphotericin B): Amphotericin B self-associates forming hydrophilic cylindrical pores that cross the membrane. This collapses selective permeability, causing massive intracellular loss of potassium ions (K+), magnesium and essential macromolecules, inducing fungal cell lysis in a fungicidal manner.
- Inhibition of Essential Transporters by Natamycin: Natamycin, upon binding to ergosterol, does not form classic pores, but rather alters the function and physical structure of the transporters and enzymes attached to the fungal membrane, preventing endocytosis and the absorption of essential nutrients. It is the only antifungal approved by the FDA for keratitis due to filamentous fungi (Fusarium, Aspergillus).
Pharmacokinetics
Quantitative Ocular and Systemic Pharmacokinetics
| Parameter | Natamycin 5.0% (Suspension) | Amphotericin B 0.15% - 0.25% (F. Magistral) |
|---|---|---|
| Formulation | Stable aqueous suspension; requires constant vigorous stirring beforehand. | Sterile ophthalmic solution prepared under a hood (photosensitive). |
| Cornea Penetration | Extremely poor in intact stroma; adheres to the corneal surface. | Poor penetration into deep corneal stroma; requires debridement. |
| Tmax and Interval | Maximum surface concentrations in 30-60 min; requires hourly doses. | Rapid maximum concentration in epithelial wound; hourly dosage. |
| Plasma Bioavailability | Non-existent after the usual conjunctival topical dosage. | Non-existent at conventional topical ophthalmic doses. |
| Half-life in Previous Segment | t1/2 on corneal surface ≈ 1.5 - 2 h on average. | Rapid clearance of the anterior corneal stroma. t1/2 ≈ 1.0 h. |
Deep Fungal Infiltrate and Therapeutic Corneal Debridement
Due to the high molecular weight and insoluble nature of polyene macrolides (especially natamycin), their penetration through an intact corneal epithelium is almost non-existent. In aggressive fungal keratitis with a deep stromal course, the fungus grows longitudinally and radially in the stromal matrix, outside the reach of the topical antifungal. To ensure the delivery of effective bactericidal concentrations of natamycin or amphotericin B, therapeutic corneal debridement (epithelial scraping) should be performed periodically in consultation under topical anesthesia. This mechanical technique eliminates the lipophilic epithelial barrier, allowing direct infusion of the antifungal into the affected stroma.
Security
Contraindications
- Absolute: Documented hypersensitivity to amphotericin B or natamycin eye drops.
- Relative: Absence of precise microscopic or clinical fungal diagnosis (its high local toxicity discourages irrational empirical use).
Adverse Effects (ADR)
- Ocular Sites: Severe epitheliotoxicity and acute pain immediately after application; ulcerative punctate keratopathy; mild chemical conjunctival necrosis (with amphotericin of inadequate concentration); reflex tearing and marked conjunctival hyperemia; intense dural photophobia.
- Systemic: Nonexistent at usual topical ophthalmic doses.
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
- Ocular Antifungal Agents