[Hepatotoxicity of antimicrobial agents. II: Urinary antiseptics, antitubercular agents, antiparasitic agents, antifungal agents, antiviral agents].
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Anti-Infective Agents, Urinary↗
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[Progress in chemotherapeutic agents--antifungal agents].
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Amphotericin B↗
Hepatotoxicity of antifungal agents.
Antifungal agents have been implicated in numerous cases of hepatotoxicity throughout the past few decades. Hepatotoxic reactions to antifungal agents range from slight, asymptomatic abnormalities in liver function tests to potentially fatal fulminant hepatic failure. Clinically significant hepatic injury resulting from antifungal therapy most commonly manifests as acute hepatocellular, cholestatic or mixed hepatocellular-cholestatic reactions. In general, reactions usually resolve on cessation of therapy, but some antifungal agents may induce chronic liver damage. This review will summarize the hepatotoxicity profiles of the major classes of antifungal agents and will provide recommendations for drug monitoring in order to minimize the risk of hepatotoxicity.
Allylamine↗
[Fungal infections of the eye--current antifungal agents].
Antifungal agents used in ocular infections are presented. The most common etiology of fungal infections is described. Mechanisms and range of action, available drugs and the latest groups of antifungal agents during clinical trials are presented.
Antifungal Agents↗
Interaction between Candida agglutinins and antifungal agents.
Antifungal agents alter the function and morphology of Candida cell membranes and cell walls. We observed that brief (30 minute) exposure to either amphotericin B or clotrimazole inhibited the agglutination of Candida blastoconidia by murine bronchoalveolar lavage fluid. This inhibition required continuous drug presence. Neither amphotericin nor clotrimazole inhibited Candida agglutination by concanavalin A or pooled human serum. These results demonstrate that antifungal drugs can produce rapid changes in the surface characteristics of some fungi.
Agglutination↗
[The future of antifungal agents. Non azole antifungal agents].
We investigated the efficacy of non-azole antifungal agents. Long circulating immunoliposomal amphotericin B was potent in murine invasive pulmonary aspergillosis. The concentration of AMPH-B was still high in the lung after 6 hours of 34A-PEG-liposomal AMPH-B. Lipid nanosphere amphotericin B (NS-718) showed efficacy against pulmonary aspergillosis in rats and pulmonary cryptococcosis in mice. The renal toxicity of NS-718 was estimated to be lower than that of AMPH-B from the results of the toxicity study in the rat infusion model. FK 463, a novel (1,3)-beta-D-glucan synthase inhibitor, showed efficacy against azole-resistant Candida albicans in murine experimental disseminated candidiasis. FK463 could be a promising drug and the therapy of choice for azole resistant C. albicans infection.
Amphotericin B↗
Clinical significance of interactions with antifungal agents.
Antifungal drugs act by a variety of mechanisms. Agents such as substituent imidazoles and triazoles, which act by inhibiting the fungal cytochrome P-450-dependent enzyme lanosterol N-demethylase, have the potential to inhibit host cytochrome P-450-dependent drug metabolism. This is discussed with respect to ketoconazole, fluconazole and itraconazole. In contrast, allylamines, which have a different mode of action and a weaker ability to bind to cytochrome P-450, are not expected to inhibit clinical drug oxidation. Inducers of drug metabolism, especially rifampicin, phenobarbitone and phenytoin, may lower plasma (and tissue) concentrations of those antifungals metabolized by mixed function oxidases, with therapeutic consequences.
Antifungal Agents↗
Treatment of dermatological conditions with a combination of an antibacterial agent, an antifungal agent and an antiinflammatory steroid.
Thirty-eight patients suffering from dermatological conditions of various natures were treated by means of the simultaneous application of a combination of three creams, the bases of which were sodium fusidate, ketoconazole and clobetasone butyrate respectively. Positive results, in the form of remission of symptoms, were obtained in 86.7% of the cases. Local tolerance was excellent in all cases and no adverse reactions were observed.
Administration, Topical↗
Treatment of onychomycosis: pros and cons of antifungal agents.
BACKGROUND: Antifungal agents are beneficial in the treatment of onychomycosis in the general population, as well as in children, the elderly, and immunocompromised individuals. Special patient populations can be more difficult to treat due to such factors as drug interactions with concomitant medications, adverse events, and poor compliance. In addition, there is limited information about the use of antifungal agents in special populations, e.g., children. OBJECTIVE: The pros and cons of oral and topical antifungal agents are discussed, with focus on special patient populations. METHODS: We searched MedLine (1966 to April 2003) for clinical studies evaluating the efficacy of oral and topical antifungal agents to treat onychomycosis. The key words used in conjunction with "onychomycosis" include: "terbinafine," "itraconazole," "fluconazole," "amorolfine nail lacquer," "ciclopirox nail lacquer," "HIV," "transplant patients," "diabetes," "children," and "elderly." Studies were excluded if published in a language other than English. RESULTS: Studies have shown that antifungal agents can be of benefit in treating the elderly, children, and immunocompromised individuals (e.g., transplant patients, Down's patients, HIV patients, and diabetics) with onychomycosis. CONCLUSION: The treatment modality of onychomycosis in special patient populations should take into account the clinical presentation of the onychomycosis, the causative organism, patient and physician preference, the concomitant medications that the patient is on, and the potential for adverse events for that patient if antifungal therapy is undertaken.
Administration, Oral↗
[Use of topical antifungal agents].
Topical antifungal agents are not absorbed when given orally. They act by direct contact on the fungus, this type of action requires the simultaneous presence of antifungal and fungus for a minimum of time. There are a large number of compounds belonging to different families of antifungals: polyens, azoles, allylamine and morpholine and antiseptic substances. The treatment of oropharyngeal candidiasis is based on topical antifungal agents: amphotericin B or nystatin, imidazoles such as clotrimazole or miconazole. Systemic antifungal agents are indicated in case or poor compliance to topical agents, in prophylaxis of highly relapsing disease, in oesophageal candidiasis and in Candida onychomycosis. A topical antifungal agent is the first choice to treat Candida intertrigo. In any case predisposing factors should be eradicated or amended. Infection to Malassezia spp. are treated topically with azoles or selenium sulphur. Oral ketoconazole is an alternative in severe cases. Dermatophytosis requires a systemic antifungal treatment such as terbinafine in chronic, dry, moccassin type palmoplantar infection and for onychomycosis. Intertrigo and tinea corporis are treated with topical agents such as azoles, terbinafine or tolnaftate. Tinea capitis responds to oral griseofulvine, however a topical antifungal must be added to eradicate contagious conidia. Whatever the localisation is, an other superficial site of infection must be looked for and a source of infection should be investigated and eradicated.
Animals↗
Suppression of ATP in Candida albicans by imidazole and derivative antifungal agents.
Several antifungal agents, at concentrations of 10 micrograms/ml, were shown to suppress ATP concentrations very rapidly in intact cells and spheroplasts of Candida albicans. The highest ATP-suppressing activity was shown by the highly lipophilic imidazole derivatives difonazole, clotrimazole, econazole, isoconazole, miconazole, oxiconazole and tioconazole, which all caused a reduction of cellular ATP content of more than 50% in 10 min. Relatively hydrophilic imidazole derivatives such as ketoconazole were essentially inactive in the test, as were the triazole derivatives fluconazole, ICI 153066, itraconazole and terconazole, and 5-fluorocytosine. Amphotericin B and terbinafine possessed intermediate ATP-suppressing activity, and the dose-response and pH-response curves for these compounds suggested their mechanism of ATP suppression differed from that of the active imidazole derivatives. ATP suppression by azole antifungals did not involve leakage of ATP from the cells and the effect was entirely abrogated by the presence of serum. Intact cells and spheroplasts of yeast-form and hyphal-form C. albicans were generally equally sensitive to ATP suppression, but stationary-phase cells of both morphological forms were less sensitive than exponential-phase cells. The extent of ATP suppression was significantly reduced in stationary-phase yeast cells of a C. albicans strain with known resistance to azole antifungals, but exponential-phase cells of resistant and susceptible strains were equally sensitive. The effect is tentatively ascribed to membrane damage caused directly by the antifungals.
Adenosine Triphosphate↗
[Present problems and future trend of antifungals for deep seated mycosis. Azole antifungal agents].
Azole antifungal agents are the most common drugs for the treatment of deep seated mycosis throughout the world, because of their favorable anti-fungal spectrum, pharmacokinetics and safety. However there are some weak points in each drug or class, such as emerging resistance or interactions with other drugs. Many new derivatives are now under pre-clinical and clinical evaluation and among them, voriconazole and SCH56592 are showing satisfactory results in their early clinical studies. At the same time, however the ability of doctors to make an appropriate and logical choice for use of these drugs also essential.
Animals↗
[Drug discovery in the new era: exploratory research on novel antifungal agents].
The major antifungal agents currently used in clinics fall into classes of either antibiotics or azoles. Recent introduction of a candin-antibiotic, micafungin, into clinical practice is expected to greatly improve the outcome of therapy in deep mycoses. However, there still exist many mycoses which are hard to treat even with application of a variety of antifungal agents. With this situation of chemotherapy in mycoses, development of novel antifungal agents with good profiles in efficacy and safety and superior to those currently available are anticipated to be discovered by exploratory research. The major target worldwide in the research and development of novel antifungal agents is azole-class compounds. However, among the antifungal antibiotics now being developed, several compounds are being subjected to clinical evaluation based on their novel mechanisms of action and on their non-susceptible feature of cross-resistance to existing antifungal agents.
Antifungal Agents↗
The role of azole antifungal agents for systemic antifungal therapy.
Although amphotericin B remains the cornerstone of antifungal drug therapy, fluconazole and itraconazole have been found useful for long-term maintenance or prophylactic regimens. This article reviews characteristics of fluconazole and itraconazole and compares them with ketoconazole and amphotericin B.
Amphotericin B↗
Sertaconazole (FI-7045). A new antifungal agent.
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Antifungal Agents↗
Ketoconazole (Nizoral). A new antifungal agent.
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Antifungal Agents↗