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The Potential of Medicinal Plants as Treatments for Infections Caused by Aspergillus spp.
Published in Namrita Lall, Medicinal Plants for Cosmetics, Health and Diseases, 2022
Tefo K. Pule, Marco N. De Canha, Namrita Lall, Quenton Kritzinger
Although AmB is a popular treatment against aspergillosis, Jenks and Hoenigl (2018) reported that there have been a number of adverse side effects. These include nephrotoxicity, electrolyte disturbances and hypersensitivity. These are side effects which need to be considered carefully before the use of AmB. Although triazoles have a better effect than AmB treatments, patients tend to show tolerance to triazoles, and this leads to an increase in dosage (Jenks and Hoenigl, 2018). This suggests that triazoles not only might become less effective after prolonged use, but the patients who are prescribed long-term use of these treatments might become more tolerant to the drug. Moreover, the extended use of triazoles increases renal toxicity and nephrotoxicity (Alastruey-Izquierdo et al., 2018). Echinocandins are merely fungistatic for Aspergillus by preventing hyphal tip growth, and are thus reserved for patients who have failed prior treatments or have a renal impairment that would lead to the exclusion of drugs causing renal and nephrotoxicity (Maghrabi and Denning, 2017).
Onychomycosis
Published in Robert Baran, Dimitris Rigopoulos, Chander Grover, Eckart Haneke, Nail Therapies, 2021
Dimitris Rigopoulos, Robert Baran
Efinaconazole 10% solution was FDA approved as a treatment in 2014. It is a triazole antifungal that inhibits the synthesis of ergosterol in the fungal cell wall. Its indication is the treatment of toenail onychomycosis due to T. rubrum and T. mentagrophytes. Reported mycological cure rates are 53.4%–55.2% and complete cure rates 15.2%–17.8%. It is applied daily for 48 weeks and no removal, filing, or trimming is necessary.
Heterocyclic Drugs from Plants
Published in Rohit Dutt, Anil K. Sharma, Raj K. Keservani, Vandana Garg, Promising Drug Molecules of Natural Origin, 2020
Debasish Bandyopadhyay, Valeria Garcia, Felipe Gonzalez
Fluconazole (Figure 8.13) is an antibiotic, frequently used in treating fungal and yeast infections (Fluconazole, 2018). This drug belongs to the triazole class of antifungal agents which works by inhibiting/reducing the fungal growth that causes infection in the human body. Substantial clinical studies demonstrated fluconazole’s effectiveness, its favorable pharmacokinetics, and safety profile; all these have a large contribution to its widespread uses (Cha et al., 2004). This drug works well in fungal meningitis and as a preventive medicine for infections due to chemotherapy, radiation therapy, or bone marrow transplant (Fluconazole, 2018). It also demonstrated activity up to a certain extent for the treatment of fungal infections in HIV positive patients. Fluconazole is taken orally but it some cases intravenous administration is preferred (Zervos et al., 1993).
Bromuconazole fungicide induces cell cycle arrest and apoptotic cell death in cultured human colon carcinoma cells (HCT116) via oxidative stress process
Published in Biomarkers, 2022
Karima Rjiba-Touati, Imen Ayed-Boussema, Hiba Hamdi, Awatef Azzebi, Salwa Abid
Bromuconazole, a fungicide belonging to the triazole family, is one of the most effective fungicides to treat several fungal contaminations observed in barley, wheat and fruits in post-harvest treatment (Menegola et al. 2005; Jawed et al. 2019). This triazole acts by inhibiting C-14 alpha-demethylase, an enzyme essential for the synthesis of ergosterol in fungi (EFSA, 2008; Edwards and Godley 2010; Sun et al. 2006; Tully et al. 2006). Due to its high accumulation in the environment and the exposure of the general population to contaminated foodstuffs, bromuconazole may represent a risk factor not only for targeting fungi but also for animals and for human health (Mokhbatly et al. 2019). Bromuconazole, classified by the World Health Organisation as a moderately dangerous fungicide belonging to class II, is rapidly absorbed from the gastrointestinal tract, widely distributed to tissues such as liver, kidney and brain (Mazur et al. 2007, EFSA, 2010). A previous study reported that bromuconazole caused organs damage and exhibit carcinogenic potential with prolonged exposure (Mokhbatly et al. 2019; Abdelhadya et al. 2017). Since little information is available about bromuconazole toxic effect in vitro, the mechanism of toxicity adopted by this compound and its eventual cellular targets remains not well characterised.
Hepatic safety of the antifungal triazole agent posaconazole: characterization of adverse event reports in a manufacturer’s safety database
Published in Expert Opinion on Drug Safety, 2022
Rose O’Flynn, Yun-Ping Zhou, Hetty Waskin, Ronald Leong, Walter Straus
Triazole antifungal agents have been associated with hepatic adverse events (AEs) that may affect their clinical utility [13–16]. Drug-induced liver injury (DILI) typically manifests as abnormal hepatic function test results and associated symptoms and may represent a significant safety risk to patients. Information about hepatic safety is important in characterizing the overall benefit-risk profile of triazole antifungal agents, particularly because these products are frequently used in frail patient populations. Hepatic adverse reactions (eg, mild to moderate elevations in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin levels, and/or clinical hepatitis) have been reported in clinical trials with posaconazole [17]. The elevations in liver function values as defined in the US prescribing information for posaconazole were generally reversible when therapy was discontinued; in some instances, these elevations normalized without drug interruption [17]. The literature is limited regarding the hepatobiliary safety of posaconazole in real-world practice [18–20].
How urgent is the need for new antifungals?
Published in Expert Opinion on Pharmacotherapy, 2021
Adam G. Stewart, David L. Paterson
Fluconazole and posaconazole are the main antifungals used for primary prophylaxis for hematological malignancy and HSCT. Posaconazole has demonstrated a mortality (8% versus 2%) and cumulative risk of infection benefit in acute myeloid leukemia and myelodysplastic syndrome [214]. Inhaled formulations of amphotericin B is used as prophylaxis in the lung transplant patient population with little data advocating for systemic azole use [212,215]. Toxicities associated with prophylactic antifungals is sizable. Inhaled amphotericin B is associated with cough, dyspnea, bronchospasm, wheezing and nausea [215]. Long-term triazole use has been associated with hepatotoxicity, peripheral neuropathy, alopecia, periostitis, and squamous cell carcinomas [216]. The need for therapeutic drug monitoring of some triazoles with regards to erratic and inconsistent absorption is also problematic. Concerns have been raised over rising azole-resistance and breakthrough invasive fungal infections. A study of 95 patients who underwent 202 courses of primary antifungal prophylaxis with posaconazole observed 13% (27/202) breakthrough their regimen; this proportion was significantly higher when compared with historical data [217]. This represents a shift to non-Aspergillus spp. (in particular mucormycetes) as a cause of fungal infection. These issues with current prophylactic regimens have sparked new interest into the development of novel agents to be used as prophylaxis in high-risk patients