Antifungals
Fungal skin infections (dermatophytosis, candidiasis, pityriasis versicolor) are common superficial conditions, but they come back easily if the responsible fungus is not correctly identified and treatment is not completed. Antifungal drugs work either by disrupting the integrity of the fungal cell membrane or by interfering with fungal cell division. Whether to use a topical or an oral antifungal depends on where the infection is, how widespread it is and how well each drug penetrates keratinized tissue.
At Haute-Derma, fungal skin infections are managed to a standard protocol: direct microscopy for fungal elements, identification of the fungal species and, for systemic treatment, close monitoring of liver function and CYP450 drug interactions.
How Antifungals Work: Mechanisms and Pharmacodynamics
Blocking Cell Membrane Synthesis (Ergosterol Synthesis)
Ergosterol is the key structural component that keeps the fungal cell membrane stable:
- Squalene epoxidase inhibitors (allylamines and thiocarbamates): Terbinafine and naftifine block squalene epoxidase, preventing squalene from being converted to squalene epoxide. Squalene builds up inside the cell to toxic levels and the fungus dies quickly (fungicidal effect).
- Lanosterol 14-alpha-demethylase inhibitors (azoles): Ketoconazole, itraconazole and fluconazole inhibit this cytochrome P450-dependent enzyme, stopping lanosterol from being converted to ergosterol. Without enough ergosterol, the fungal membrane loses its normal permeability and function (fungistatic effect).
Damaging the Cell Membrane and Disrupting the Mitotic Spindle
- Microtubule inhibitors (griseofulvin): Binds to tubulin, disrupting formation of the mitotic spindle and halting the fungal cell cycle in metaphase.
- Direct ergosterol binding (polyenes): Nystatin and amphotericin B bind directly to ergosterol and form pores in the cell membrane, so ions leak out of the cell.
Types of Antifungals Used in Dermatology
Topical Antifungals
Used for superficial infections confined to small areas, such as ringworm of the body (tinea corporis), groin (tinea cruris) or feet (tinea pedis), or pityriasis versicolor.
- Topical azoles: clotrimazole 1%, ketoconazole 2%, miconazole 2%, sertaconazole 2%.
- Topical allylamines and morpholines: terbinafine 1% (an allylamine), amorolfine 5% (a morpholine, as a nail lacquer).
- Other: ciclopirox olamine 1%.
Oral (Systemic) Antifungals
Used for nail fungus (onychomycosis), scalp ringworm (tinea capitis), widespread skin infection or when topical treatment has failed.
- Terbinafine: first choice for nail fungus and dermatophyte infections. Usual dose 250 mg/day.
- Itraconazole: broad spectrum covering dermatophytes, Candida and Malassezia. Dose 100–200 mg/day, or pulse therapy at 400 mg/day.
- Fluconazole: particularly useful for Candida infections of the skin and mucous membranes. Dose 150 mg/week.
Pharmacological Comparison of Common Antifungals
| Drug (Generic) | Main Spectrum | Main Mechanism |
|---|---|---|
| Terbinafine | Dermatophytes (very potent) | Squalene epoxidase inhibition |
| Itraconazole | Dermatophytes, Candida, Malassezia | Lanosterol 14-alpha-demethylase inhibition |
| Fluconazole | Candida spp., Pityrosporum | Lanosterol 14-alpha-demethylase inhibition |
| Ketoconazole | Malassezia, Candida, dermatophytes | Lanosterol 14-alpha-demethylase inhibition |
| Amorolfine | Nail infections caused by dermatophytes and yeasts | Morpholine: inhibits membrane sterol synthesis (Δ14-reductase and Δ7,Δ8-isomerase) |
Managing Drug Interactions and Liver Toxicity
- Cytochrome P450 (CYP3A4) inhibition: Oral triazoles, especially itraconazole, strongly inhibit hepatic CYP3A4. This raises blood levels of other drugs taken at the same time, such as statins, warfarin, cyclosporine and midazolam, with a risk of toxicity from the combination.
- Liver toxicity (hepatotoxicity): Oral antifungals can cause progressively rising liver transaminases. Liver function tests (AST, ALT) are needed before treatment and again after 4–6 weeks for courses longer than 1 month.
- Stomach acid: Itraconazole capsules need an acidic stomach to dissolve and be absorbed. They should not be taken together with antacids or proton pump inhibitors (PPIs).
Treatment and Monitoring at Haute-Derma
Confirming the diagnosis: Every patient with a suspected fungal infection has direct microscopy with 10–20% KOH to look for spores and septate hyphae before anything is prescribed.
Treatment by Body Site
- Body or groin ringworm: terbinafine 1% or ciclopirox 1% applied once or twice daily for 2–4 weeks, extending 2 cm beyond the edge of the rash.
- Fingernail or toenail fungus: oral terbinafine 250 mg/day for 6 weeks (fingernails) or 12 weeks (toenails), or pulse itraconazole 400 mg/day for 1 week each month, combined with nail filing and amorolfine 5% lacquer.
Hygiene and Preventing Recurrence
- Keep the affected skin dry and well ventilated, and avoid tight or damp clothing.
- Disinfect shoes and socks with an antifungal product, or replace them, to remove lingering fungal spores.
