Alternariosis is an infection by Alternaria, presenting cutaneously as focal, ulcerated papules and plaques.[1]:330
Treatment with itraconazole has been reported.[2]
https://en.wikipedia.org/wiki/Alternariosis
Itraconazole, sometimes abbreviated ITZ, is an antifungal medication used to treat a number of fungal infections.[5] This includes aspergillosis, blastomycosis, coccidioidomycosis, histoplasmosis, and paracoccidioidomycosis.[5] It may be given by mouth or intravenously.[5]
Common side effects include nausea, diarrhea, abdominal pain, rash, and headache.[5] Severe side effects may include liver problems, heart failure, Stevens–Johnson syndrome and allergic reactions including anaphylaxis.[5] It is unclear if use during pregnancy or breastfeeding is safe.[1] It is in the triazole family of medications.[5] It stops fungal growth by affecting the cell membrane or affecting their metabolism.[5]
Itraconazole was patented in 1978 and approved for medical use in the United States in 1992.[5][6] It is on the World Health Organization's List of Essential Medicines.[7]
Recent research works suggest itraconazole (ITZ) could also be used in the treatment of cancer by inhibiting the hedgehog pathway.[8]
Itraconazole has a broader spectrum of activity than fluconazole (but not as broad as voriconazole or posaconazole). In particular, it is active against Aspergillus, which fluconazole is not. It is also licensed for use in blastomycosis, sporotrichosis, histoplasmosis, and onychomycosis. Itraconazole is over 99% protein-bound and has virtually no penetration into cerebrospinal fluid. Therefore, it should not be used to treat meningitis or other central nervous system infections.[9] According to the Johns Hopkins Abx Guide, it has "negligible CSF penetration, however treatment has been successful for cryptococcal and coccidioidal meningitis".[10]
It is also prescribed for systemic infections, such as aspergillosis, candidiasis, and cryptococcosis, where other antifungal drugs are inappropriate or ineffective.
In the past decade, itraconazole has been explored as an anticancer agent for patients with basal cell carcinoma, non-small cell lung cancer, and prostate cancer.[11] For example, in a phase II study involving men with advanced prostate cancer, high-dose itraconazole (600 mg/day) was associated with significant PSA responses and a delay in tumor progression. Itraconazole also showed activity in a phase II trial in men with non-small cell lung cancer when it was combined with the chemotherapy agent, pemetrexed.[12][13][14] A recent review has also highlights its use topically and orally in conjunction with other chemotherapeutic agents for advanced and metastatic basal cell carcinomas that cannot be treated surgically.[15]
Pharmacodynamics[edit]
The mechanism of action of itraconazole is the same as the other azole antifungals: it inhibits the fungal-mediated synthesis of ergosterol, via inhibition of lanosterol 14α-demethylase. Because of its ability to inhibit cytochrome P450 3A4 CC-3, caution should be used when considering interactions with other medications.[22]
Itraconazole is pharmacologically distinct from other azole antifungal agents in that it is the only inhibitor in this class that has been shown to inhibit both the hedgehog signaling pathway[23][24] and angiogenesis.[25][26] These distinct activities are unrelated to inhibition of the cytochrome P450 lanosterol 14 alpha-demethylase and the exact molecular targets responsible remain unidentified. Functionally, the antiangiogenic activity of itraconazole has been shown to be linked to inhibition of glycosylation, VEGFR2 phosphorylation,[26] trafficking,[27] and cholesterol biosynthesis pathways.[25] Evidence suggests the structural determinants for inhibition of hedgehog signaling by itraconazole are recognizably different from those associated with antiangiogenic activity.[28]
Pharmacokinetics[edit]
Itraconazole, like cyclosporine, quinidine, and clarithromycin, can inhibit P-glycoprotein, causing drug interactions by reducing elimination and increasing absorption of organic cation drugs. With conventional itraconazole preparations serum levels can vary greatly between patients, often resulting in serum concentrations lower than the therapeutic index.[29] It has therefore been conventionally advised that patients take itraconazole after a fatty meal rather than prior to eating.[30][31]
A product (Lozanoc) licensed through the European union decentralised procedure[32] has increased bioavailability, decreased sensitivity to co ingestion of food, and hence decreased variability of serum levels.
Itraconazole was approved for medical use in the United States in 1992.[35]
It was designated an orphan drug by the both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).[36][37][38][39][40]
https://en.wikipedia.org/wiki/Itraconazole
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