Allylamines terbinafine

Due to the divergence of fungal diseases, there is neither single best treatment nor a superior drug for all diseases. However, a superior drug does exist for dermatomycoses caused by dermatophytes, namely the allylamine terbinafine (TER). For the treatment of deep mycoses in immunosuppressed patients the most efficacious drug is the polyene Amph B. 

Terbinafine and naftifine are allylamines available as topical creams (see Chapter 61). Both are effective for treatment of tinea cruris and tinea corporis. These are prescription drugs in the USA. 

Naftifine hydrochloride and terbinafine (Lamisil) are allylamines that are highly active against dermatophytes but less active against yeasts. The antifungal activity derives from selective inhibition of squalene epoxidase, a key enzyme for the synthesis of ergosterol (see Figure 48-1). 

Terbinafine (Lamisil) is an allylamine with activity similar to that of naftifine hydrochloride. It is available as a 1% cream and solution for the topical treatment of dermatophyte infections. 

Terbinafine (Lamisil) is an allylamine antifungal agent that has been shown to be quite effective for the treatment of onychomycosis. Recommended oral dosing consists of 250 mg daily for 6 weeks for fingernail infections and 12 weeks for toenail infections. Recent reports of serious hepatic toxicity, including liver failure and death, have led to recommendations that patients receiving terbinafine for onychomycosis be monitored closely with periodic laboratory evaluations for possible hepatic dysfunction. 

Terbinafine is an allylamine derivative with a broad spectrum of antifungal activity. 

Over-the-counter antifungus (fungistatic or fungicidal) medications typically include active ingredients such as allylamines (e.g., butenafine [benzylamine derivative], terbinafine), azoles (e.g., clotrimazole, micon-... 

Nussbaumer, R, Leitner, I., Mraz, K., Stutz, A. Synthesis and structure-activity relationships of side-chain-substituted analogs of the allylamine antimycotic terbinafine lacking the central amino function. J. Med. Chem. 1995, 5S(10), 1831-1836. 

Since ergosterol is used in the formation of the leishmanial cell membrane, inhibition of ergosterol biosynthesis has been considered as a useful target for chemotherapeutic attack. Allylamines (eg. terbinafine) and imidazole antifungals (eg. ketoconazole) have been found to interfere with different steps in the biosynthetic pathway of C28 sterols in leishmania and fungi. Allylamines inhibit the microsomal squalene 2,3-epoxidase and, therefore, inhibit the synthesis of squalene epoxide, the precursor of lanosterol. Imidazoles, on other hand, inhibit cytochrome P-450 dependent C-14 demethylation of lanosterol leading to decreased or no synthesis of ergosterol [30]. 

The azoles miconazole (Micatin, others) and econazole (Spectrazole, others) and the allylamines naftifine (Naftin) and terbinafine (Lamisil, others) are effective topical agents for the treatment of localized tinea corporis and uncomplicated tinea pedis. Topical therapy with the azoles is preferred for localized cutaneous candidiasis and tinea versicolor. 

Topical therapy with the azoles and allylamines is effective for tinea pedis. Macerated toe web disease may require the addition of antibacterial therapy. Econazole nitrate, which has a limited antibacterial spectram, can be useful in this situation. Systemic therapy with griseofulvin, terbinafine, or itraconazole (Sporanox, others) is used for more extensive tinea pedis. It should be recognized that long-term topical therapy may be necessary in some patients after courses of systemic antifungal therapy. 

Terbinafine is a synthetic allylamine, structurally similar to the topical agent naftifine. 

Ryder, N. "Recent Advances with the Allylamine Antimycotic, Terbinafine", Abstracts of Papers, The 1995 Antifungal Drug Discovery Summit, Princeton, NJ Strategic Research Institute New York, New York, 1995. 

Terbinqfine is a synthetic allylamine that is structurally similar to naftifine. It probably acts by inhibiting fungal squalene epoxidase and blocking ergosterol biosynthesis. Terbinafine is well absorbed, but bioavailability is only 40% because of first-pass hepatic metabolism. Proteins bind... 

Butenafine hydrochloride (mentax) is a benzylamine derivative with a mechanism of action and spectrum of antifungal activity similar to those of terbinafine, naftifine, and other allylamines. 

Unea pedis Azoles, allylamines Griseofulvin, terbinafine, itraconazole, fluconazole... 

Many of the enzymes in the sterol biosynthesis pathway have selective-inhibitors (Fig. 3). These include some extremely important classes of drugs such as Statins , used to treat high cholesterol, bisphosphonates, used to treat osteoporosis, allylamines (e.g., terbinafine) and azoles used to treat fungal infections, and morpholines which are used as fungicidal agrochemicals. 

Table 17.24 shows that inhibitors of squalene epoxidase belong to two different chemical classes. The allylamines consist of two compounds used as antimycotics against a wide range of fungi. Terbinafine is used in topical and oral uses whereas naftifine is restricted to topical uses. 

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