allylamines

Mechanism: Allylamines inhibit squalene epoxidase, an enzyme that converts squalene to lanosterol in the ergosterol synthesis pathway (ergosterol is essential for fungal cell membrane integrity). This inhibition leads to two effects: (1) depletion of ergosterol, impairing membrane function, and (2) toxic intracellular accumulation of squalene, which is directly fungicidal. This differs from azoles, which inhibit a later step (lanosterol 14-alpha-demethylase, a cytochrome P450 enzyme) and are generally fungistatic.

Key drug: Terbinafine (oral and topical) is the prototype; naftifine and butenafine are topical only.

Clinical uses: Terbinafine is first-line for onychomycosis (nail fungus, usually caused by dermatophytes like Trichophyton) and is also used for tinea corporis, tinea cruris, and tinea pedis. It is fungicidal against dermatophytes but less effective against Candida (fungistatic).

Pharmacokinetics: Oral terbinafine is lipophilic, accumulates in skin, nails, and fat; it has a long half-life allowing for pulse dosing in onychomycosis treatment.

Adverse effects: Hepatotoxicity (requires LFT monitoring with oral use), GI upset, headache, taste disturbances (dysgeusia), and rare cases of Stevens-Johnson syndrome. Unlike azoles, terbinafine has minimal effect on human cytochrome P450 enzymes, so fewer drug interactions.

High-yield comparison: Azoles inhibit 14-alpha-demethylase (a human-shared CYP450 enzyme, causing more drug interactions), while allylamines inhibit squalene epoxidase (a fungal-specific enzyme not involving CYP450), giving a better interaction profile.