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Tolnaftate
Published in Anton C. de Groot, Monographs in Contact Allergy, 2021
Tolnaftate is a thiocarbamate derivative with either fungicidal or fungistatic properties. It is a selective, reversible and non-competitive inhibitor of membrane-bound squalene 2,3-epoxidase, an enzyme involved in the biosynthesis of ergosterol. Inhibition leads to the accumulation of squalene and a deficiency in ergosterol, an essential component of fungal cell walls, thereby increasing membrane permeability, disrupting cellular organization and causing cell death. In addition, this agent may also distort the hyphae and stunts mycelial growth in susceptible fungi. Tolnaftate is (or was) used to treat fungal skin infections caused by dermatophytes; it is not effective against Candida albicans (1). In the 1970s, over 75% of the prescriptions written in the U.S.A. for an antifungal agent specified tolnaftate (6).
Tolnaftate
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Tolnaftate is an old synthetic topical thiocarbamate antifungal agent with the chemical name 2-naphthyl N-methyl-N-(3-tolyl)thionocarbamate (Adam and Craig, 1965); the chemical structure is shown in Figure 162.1. Clinical use of tolnaftate has declined with the introduction of more potent antifungal compounds such as terbinafine and naftifine. Tolnaftate is used primarily for the treatment of mild to moderate tinea pedis, tinea cruris, tinea corporis, and tinea versicolor (Anon, 1966). It is not indicated for the treatment of onychomycosis due to the lack of drug penetration through the nail plate. Tolnaftate has been successfully used in the treatment of otitis externa caused by certain fungi such as Aspergillus spp. (Zarowny et al., 1975; Liston and Siegel, 1986).
Implementing polymeric pseudorotaxanes for boosting corneal permeability and antiaspergillus activity of tolnaftate: formulation development, statistical optimization, ex vivo permeation and in vivo assessment
Published in Drug Delivery, 2022
Diana Aziz, Sally Mohamed, Saadia Tayel, Amal Makhlouf
Tolnaftate (TOL) is a synthetic thiocarbamate antifungal agent acts selectively by inhibiting squalene epoxidase, an important microsomal enzyme in biosynthetic pathway of ergosterol (an essential component of the fungal membrane). Thus, squalene is accumulated in the cell wall of the fungi and ergosterol is depleted which affects membrane permeability, membrane-bound enzymes and growth causing cell death (Abdelbary et al., 2016; Abousamra & Mohsen, 2016). Furthermore, it is active against filamentous fungi e.g., Aspergillus spp. which are among the most common causes of mycotic keratitis. Aspergillus, if not early diagnosed, can also cause reduction in visual capacity due to its early macular involvement, choroidal damage and retinal necrosis (Spadea & Giannico, 2019). Hence, TOL is expected to be a promising candidate for the treatment FK due to its selective fungicidal properties, intermediate molecular mass (307.4) and lipophilicity (log P 5.5) which facilitate its penetration across the corneal lipid rich epithelial and endothelial cell membrane (Kaur et al., 2008). However, being a biopharmaceutical classification system (BCS) IV drug, TOL possesses low aqueous solubility (0.00054 mg/mL) and penetration which act as obstacles that limit its clinical ocular efficacy (Akhtar et al., 2016). Hence, the challenge is to formulate TOL in an appropriate delivery system to enhance its aqueous solubility and consequently promoting its ocular permeation and retention.
Nanotechnological interventions in dermatophytosis: from oral to topical, a fresh perspective
Published in Expert Opinion on Drug Delivery, 2019
Riya Bangia, Gajanand Sharma, Sunil Dogra, Om Prakash Katare
Another problem involved with the treatment of dermatophytosis is the adverse effects caused by the antifungal therapy. The topical antifungal agents including azoles such as miconazole were reported to cause itching, burning, or irritation of the skin. Similar effects were observed with econazole as well as ketoconazole, including itching, burning, and redness in case of econazole and dry skin, itching, dry or oily scalp, and stinging [85]. Nystatin, on applying to skin, was reported to show problems, including burning, rashes, itching, redness, and pustular eruption [86]. Tolnaftate was reported to cause skin irritation. Terconazole, formulated as a cream, causes skin burning or skin irritation sometimes [73]. Besides these, systemic antifungal agents can cause severe side effects. The use of triazoles, including fluconazole and itraconazole, is associated with a plethora of side effects including headache, diarrhea, dizziness, stomachache, heartburn, and alterations in the ability to taste food and even more serious side effects including excessive tiredness, loss of appetite, vomiting, tingling sensation, or numbness in the extremities, urticaria, and angioedema, difficulty in swallowing, fever, and chills. Terbinafine exhibited similar side effects as that of triazoles. Griseofulvin is reported to be associated with problems, such as aplastic anemia and headache [87]. Moreover, systemic antifungal agents are contraindicated during pregnancy and must be carefully used in patients with severe hepatic and renal insufficiency [88]. A 10% incidence of adverse effects was reported when terbinafine, 250 mg/day, was administered orally to treat superficial skin infections. These effects included mild-to-moderate gastrointestinal effects and changes in liver function, which were observed rarely; however, levels of liver enzymes in plasma reverted to normal after discontinuation of treatment [89]. On the administration of terbinafine, incidences of taste loss persisting for many weeks have occurred [90]. In case of fluconazole, around 10% of patients have experienced side effects, majorly headache and gastric upset [16,91]. Another antifungal drug, itraconazole, which is reported to be well tolerated, has shown side effects in around 7% of patients administered, including headache and disturbances in gastrointestinal tract. Besides this, abnormalities in liver enzyme levels have been reported in patients administered with itraconazole which occurred within 10 days after initiating the therapy [92,93].