General characteristics and mechanism of action
The triazole group includes such medications as itraconazole, fluconazole, voriconazole, terconazole, posaconazole, and ravuconazole, which is currently undergoing clinical trials. The main difference between triazoles and older imidazoles is their higher selectivity for fungal 14$\alpha$-demethylase.
Due to this feature, triazoles practically do not affect the human enzyme 17,20-desmolase, which avoids disruptions in the synthesis of sex hormones and glucocorticoids.
Itraconazole and fluconazole: features of use
Itraconazole successfully replaces ketoconazole in systemic mycoses and dermatomycoses. Its absorption directly depends on gastric acidity: capsules are taken with a heavy meal, while the solution is taken on an empty stomach. The drug actively accumulates in the skin and nails, but penetrates poorly into biological fluids.
Fluconazole is the most demanded antifungal drug with a bioavailability of about 100%. Unlike itraconazole, its absorption does not depend on gastric juice pH, and the drug freely penetrates all body fluids, including CSF. This makes it the drug of choice for systemic candidiasis and cryptococcal meningitis.
Voriconazole and posaconazole
Voriconazole has one of the broadest spectrums of activity among oral agents and serves as the drug of choice for invasive aspergillosis and infections caused by Fusarium and Scedosporium. A feature of the intravenous form of voriconazole is the presence of the excipient sulfobutyl ether beta-cyclodextrin, which is why it is not recommended in renal failure.
Posaconazole exhibits potent fungicidal activity and is used for the prophylaxis of candidiasis and aspergillosis in patients over 13 years of age with prolonged neutropenia or severe graft-versus-host disease.
Safety and drug interactions
Triazole therapy requires medical supervision due to pronounced pharmacokinetic interactions and adverse effects:
- Metabolism: The drugs actively affect the cytochrome P450 system, increasing the concentration of agents such as warfarin, phenytoin, and cyclosporine.
- Inductors: Rifampicin, ritonavir, and barbiturates can decrease the concentration of antifungal components in the blood.
- Adverse reactions: Hepatotoxicity, dyspeptic disorders, alopecia during long-term courses, and severe conditions like Stevens-Johnson syndrome are possible.
Triazoles "Protect Hormones": high selectivity for fungal 14$\alpha$-demethylase spares human 17,20-desmolase.
Class and exam questions
What is the main clinical difference between triazoles and imidazoles?
Triazoles possess higher selectivity for fungal 14$\alpha$-demethylase and practically do not block the human enzyme 17,20-desmolase, thereby avoiding disruption of sex hormone and glucocorticoid synthesis.
Why is fluconazole the drug of choice in cryptococcal meningitis?
Fluconazole has high penetration into the cerebrospinal fluid (CSF) and a low toxicity profile, allowing for effective treatment of meningeal infections.
What are the absorption features of itraconazole?
Itraconazole absorption depends on gastric acidity. Capsules are taken with a heavy meal for maximum absorption, while the special solution is taken on an empty stomach.
What causes the limitations of intravenous voriconazole use?
The intravenous form of voriconazole contains sulfobutyl ether beta-cyclodextrin, which is excreted by the kidneys. In renal failure, this substance accumulates and becomes toxic to the central nervous system.
What else to study on this topic
- Mechanisms of resistance development in Candida species
- Comparative activity spectrum of itraconazole and fluconazole
- Pharmacokinetic features of voriconazole hepatic metabolism
- Effect of CYP450 inducers and inhibitors on triazole efficacy
- The role of ravuconazole as a fluconazole derivative in research
Master the entire topic in the «Pharmacology» course
This is a summary. The course covers everything tested in classes and exams.
- Complete WhiteCoat Pro study guide on "Triazoles" and 5,304 other subject pages
- Assignments and quizzes after every topic — just like in a colloquium
- AI tutor answers questions on the topic anytime
- 116 video lessons on the subject
Other topics in the section "Antifungal agents"
Free video lessons: pharmacologyShort lessons with study notes — no registration required.
Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.