Description

Terbinafine hydrochloride is a synthetic allylamine antifungal medication. It is available in oral and topical formulations (creams, sprays, gels), with the oral form primarily used for more extensive and difficult-to-treat infections. Terbinafine is highly lipophilic and has a strong affinity for keratinous tissues, such as skin, hair, and nails, where it accumulates to provide a sustained antifungal effect.

Indication

Terbinafine HCl is indicated for the treatment of various fungal infections caused by dermatophytes (a type of fungus that lives on the skin). The indication varies depending on the formulation:

• Oral Terbinafine: This is primarily used for deep-seated or extensive infections, especially those of the nails and scalp.

• • Onychomycosis (fungal nail infection): Terbinafine is considered one of the most effective oral treatments for toenail and fingernail fungal infections caused by dermatophytes.

• • Tinea Capitis (scalp ringworm): It is a common and effective treatment for this condition, particularly when caused by Trichophyton species.

• • Severe Tinea Infections: It may be used for severe cases of tinea corporis (ringworm), tinea cruris (jock itch), and tinea pedis (athlete’s foot) that have not responded to topical therapy.
• Topical Terbinafine: This is used for superficial fungal infections of the skin, such as athlete’s foot, jock itch, and ringworm.

Mechanism of Action

Terbinafine’s mechanism of action is primarily fungicidal (it kills the fungus) and is different from the azole antifungals. It works by targeting an early step in the fungal ergosterol synthesis pathway. The process is as follows:

1. Inhibition of Squalene Epoxidase: Terbinafine is a non-competitive inhibitor of the fungal enzyme squalene epoxidase. This enzyme is crucial for converting squalene to squalene epoxide, an early step in the biosynthesis of ergosterol.

2. Dual Effect: The inhibition of squalene epoxidase leads to two simultaneous effects that are lethal to the fungus:

• • Ergosterol Deficiency: By blocking the synthesis pathway, terbinafine causes a severe depletion of ergosterol, which is essential for the structural integrity and function of the fungal cell membrane.

• • Toxic Squalene Accumulation: The inhibition of the enzyme also causes a toxic accumulation of squalene inside the fungal cell. The buildup of squalene is believed to be directly toxic to the cell, further disrupting membrane function and leading to cell death.

This dual mechanism makes terbinafine a highly effective antifungal agent, particularly against dermatophytes. The drug’s selectivity for fungal squalene epoxidase over the mammalian enzyme ensures minimal effects on human cholesterol synthesis.