Antifúngicos azólicos: utilidade clínica e interações medicamentosas
Azole antifungals: clinical utility and drug interactions
DOI:
https://doi.org/10.34117/bjdv8n10-089Keywords:
infecções fúngicas, azóis, interações medicamentosasAbstract
No ambiente hospitalar, principalmente em unidades de terapia intensiva, as infecções fúngicas oportunistas representam um grande desafio a comunidade médica e científica, pois pacientes que possuem doenças de base que afetam o sistema imunológico e são submetidos a inúmeros procedimentos invasivos tem de 5 a 10 vezes maiores chances de adquirir infecções fúngicas nosocomiais. Essa problemática adquiriu características ainda mais complexas com a pandemia da COVID-19 principalmente devido ao aumento na utilização de antimicrobianos, corticosteroides e procedimentos invasivos, amplificando o risco das infecções causadas por fungos e outros patógenos. Desse modo, esta revisão narrativa tem o objetivo descrever os aspectos farmacocinéticos, farmacodinâmicos, uso clínico e interações medicamentosas dos principais agentes de uso sistêmico pertencentes a segunda geração da classe dos Azóis: fluconazol, itraconazol, posaconazol e voriconazol. O mecanismo de ação desses agentes deve-se a inibição da desmetilação da 14α-lanosterol, essencial para biossíntese de ergosterol. Diferentemente dos imidazólicos, os triazóis possuem em sua estrutura molecular dois átomos de carbono e três de nitrogênio que confere a este grupo menor toxicidade as células humanas e maior espectro de ação, tornando-os mais eficientes e seguros para uso clínico. Por fim, com o aumento da incidência de infecções fúngicas durante a Pandemia da COVID-19, os antifúngicos se tornaram alvos de atenção e preocupação devido ao número limitado de agentes que compõem esta classe. Desse modo, é imprescindível o uso seguro e racional dessa classe, bem como a ampliação nos esforços da comunidade científica na descoberta de novos agentes no intuito de combater doenças ocasionadas por microorganismos resistentes aos tratamentos tradicionais.
References
ARAÚJO, Bibiana Verlindo de. Modelagem farmacocinética-farmacodinâmica do antifúngico voriconazol. 2008.
ARENAS, Roberto; MORENO-COUTIÑO, Gabriela; WELSH, Oliverio. Classification of subcutaneous and systemic mycoses. Clinics in dermatology, v. 30, n. 4, p. 369-371, 2012.
BARDI, Tommaso et al. Nosocomial infections associated to COVID-19 in the intensive care unit: clinical characteristics and outcome. European Journal of Clinical Microbiology & Infectious Diseases, v. 40, n. 3, p. 495-502, 2021.
BELLMANN, Romuald; SMUSZKIEWICZ, Piotr. Pharmacokinetics of antifungal drugs: practical implications for optimized treatment of patients. Infection, v. 45, n. 6, p. 737-779, 2017.
BERKOW, Elizabeth L.; LOCKHART, Shawn R. Fluconazole resistance in Candida species: a current perspective. Infection and drug resistance, v. 10, p. 237, 2017.
BERTO, Caroline et al. Bases da resistência antifúngica: uma revisão comentada. Revista Uningá, v. 55, n. 3, p. 52-71, 2018.
BHATIA, Anuradha et al. Efficacy of oral terbinafine versus itraconazole in treatment of dermatophytic infection of skin–a prospective, randomized comparative study. Indian journal of pharmacology, v. 51, n. 2, p. 116, 2019.
BHATTACHARYA, M. et al. Posaconazole. Journal of Postgraduate Medicine, v. 56, n. 2, p. 163, 2010.
GIAMARELLOS-BOURBOULIS, Evangelos J. et al. Susceptibility profiles and clinical efficacy of antifungals against candida bloodstream isolates from critically ill patients: Focus on intravenous itraconazole. International journal of antimicrobial agents, v. 54, n. 4, p. 471-477, 2019.
CAMPESTRE, Cristina et al. Analysis of imidazoles and triazoles in biological samples after MicroExtraction by Packed Sorbent. Journal of Enzyme Inhibition and Medicinal Chemistry, v. 32, n. 1, p. 1053-1063, 2017.
CHEN, Lu et al. Pharmacokinetics and pharmacodynamics of posaconazole. Drugs, v. 80, n. 7, p. 671-695, 2020
CORRÊA, Josilene Chaves Ruela; SALGADO, Hérida Regina Nunes. Review of fluconazole properties and analytical methods for its determination. Critical reviews in analytical chemistry, v. 41, n. 2, p. 124-132, 2011.
CZYRSKI, Andrzej et al. The Overview on the Pharmacokinetic and Pharmacodynamic Interactions of Triazoles. Pharmaceutics, v. 13, n. 11, p. 1961, 2021.
DOLTON, Michael J. et al. Posaconazole exposure-response relationship: evaluating the utility of therapeutic drug monitoring. Antimicrobial agents and chemotherapy, v. 56, n. 6, p. 2806-2813, 2012.
DONG, Yue et al. Construction of antifungal dual-target (SE, CYP51) pharmacophore models and the discovery of novel antifungal inhibitors. RSC advances, v. 9, n. 45, p. 26302-26314, 2019.
DONNELLY, J. P.; DE PAUW, B. E. Voriconazole—a new therapeutic agent with an extended spectrum of antifungal activity. Clinical Microbiology and Infection, v. 10, p. 107-117, 2004.
Dupont, S., Lemetais, G., Ferreira, T., Cayot, P., Gervais, P., & Beney, L. (2012). Ergosterol biosynthesis: a fungal pathway for life on land?. Evolution: International Journal of Organic Evolution, 66(9), 2961-2968.
DWIVEDI, Ashish et al. Ultra-performance liquid chromatography electrospray ionization–tandem mass spectrometry method for the simultaneous determination of itraconazole and hydroxy itraconazole in human plasma. Journal of pharmaceutical analysis, v. 4, n. 5, p. 316-324, 2014.
DYBRO, Anne Mette et al. Statin-associated rhabdomyolysis triggered by drug–drug interaction with itraconazole. Case Reports, v. 2016, p. bcr2016216457, 2016.
Food and Drug Administration – FDA. (2018). FDA Drug Safety Communication: FDA to review study examining use of oral fluconazole (Diflucan) in pregnancy.
GALVAO, Jose Geraldo et al. Using the fungi Fusarium oxysporum as bioindicator of ametrine by measuring biomass and erogosterol. Ciência e Agrotecnologia, v. 27, p. 840-845, 2003.
GAMA, Mirnaluci P. Ribeiro et al. Rabdomiólise devido ao uso de estatina em altas doses: relato de caso. Arquivos Brasileiros de Endocrinologia & Metabologia, v. 49, p. 604-609, 2005.
GREER, Nickie D. Voriconazole: the newest triazole antifungal agent. In: Baylor University Medical Center Proceedings. Taylor & Francis, 2003. p. 241-248.
GUPTA, Aditya K.; FOLEY, Kelly A.; VERSTEEG, Sarah G. New antifungal agents and new formulations against dermatophytes. Mycopathologia, v. 182, n. 1, p. 127-141, 2017.
HENDRIX, Michael Joshua et al. Voriconazole versus itraconazole for the initial and step-down treatment of histoplasmosis: A retrospective cohort. Clinical Infectious Diseases, v. 73, n. 11, p. e3727-e3732, 2021.
HERSH, Elliot V. et al. Fluconazole-Warfarin Interaction: A case report with deadly consequences. Australasian Medical Journal (Online), v. 10, n. 6, p. 544, 2017.
HOLT, Anders et al. Bleeding Risk Following Systemic Fluconazole or Topical Azoles in Patients with Atrial Fibrillation on Apixaban, Rivaroxaban, or Dabigatran. The American Journal of Medicine, v. 135, n. 5, p. 595-602. e5, 2022.
IVANOV, Marija; ĆIRIĆ, Ana; STOJKOVIĆ, Dejan. Emerging Antifungal Targets and Strategies. International Journal of Molecular Sciences, v. 23, n. 5, p. 2756, 2022.
KAZEMINEJAD, Zahra et al. Novel 1, 2, 4-Triazoles as Antifungal Agents. BioMed Research International, v. 2022, 2022.
KHAN, MD Amer et al. RESPIRATORY DEPRESSION DUE TO CLONAZEPAM AND FLUCONAZOLE INTERACTION: CASE REPORT AND DISCUSSION.
KOO, Hoonmo L.; HAMILL, Richard J.; ANDRADE, Roberto A. Drug-drug interaction between itraconazole and efavirenz in a patient with AIDS and disseminated histoplasmosis. Clinical Infectious Diseases, v. 45, n. 6, p. e77-e79, 2007.
KRITSI, Eftichia et al. Novel hit compounds as putative antifungals: The case of Aspergillus fumigatus. Molecules, v. 24, n. 21, p. 3853, 2019.
LEUNG, Simon; POULAKOS, Mara N.; MACHIN, Jade. Posaconazole: an update of its clinical use. Pharmacy, v. 3, n. 4, p. 210-268, 2015.
LIPNER, Shari R.; SCHER, Richard K. Onychomycosis: Clinical overview and diagnosis. Journal of the American Academy of Dermatology, v. 80, n. 4, p. 835-851, 2019.
MAERTENS, Johan A. History of the development of azole derivatives. Clinical Microbiology and Infection, v. 10, p. 1-10, 2004.
MARZI, Mahrokh et al. A Recent Overview of 1, 2, 3-Triazole-Containing Hybrids as Novel Antifungal Agents: Focusing on Synthesis, Mechanism of Action, and Structure-Activity Relationship (SAR). Journal of Chemistry, v. 2022, 2022.
MCBRIDE, Joseph A.; GAUTHIER, Gregory M.; KLEIN, Bruce S. Clinical manifestations and treatment of blastomycosis. Clinics in chest medicine, v. 38, n. 3, p. 435-449, 2017.
MENOZZI, Cheyene Almeida Celestino et al. Otimização da síntese do fluconazol: um importante fármaco antifúngico da classe dos azóis. Revista Virtual de Química. Rio de Janeiro (RJ), v. 9, n. 3, p. 1216-1234, 2017.
MISHRA, Raghav et al. Biological potential of thiazole derivatives of synthetic origin. Journal of Heterocyclic Chemistry, v. 54, n. 4, p. 2103-2116, 2017.
DE MORAES, Sabrina Santarém; BADIN, Rebeka Caribé. Isavuconazol: um novo fármaco para tratamento de aspergilose invasiva e mucormicose: Isavuconazole: a new drug for the treatment of invasive aspergillosis and mucormycosis. Brazilian Journal of Health Review, v. 5, n. 4, p. 16644-16655, 2022.
MUNAYYER, Hanan K. et al. Posaconazole is a potent inhibitor of sterol 14α-demethylation in yeasts and molds. Antimicrobial agents and chemotherapy, v. 48, n. 10, p. 3690-3696, 2004.
NEUFELD, Paulo Murillo. A COVID-19 e o diagnóstico da aspergilose pulmonar invasiva. RBAC, v. 52, n. 2, p. 173-85, 2020.
OLUM, Ronald et al. Tolerability of oral itraconazole and voriconazole for the treatment of chronic pulmonary aspergillosis: A systematic review and meta-analysis. PloS one, v. 15, n. 10, p. e0240374, 2020.
PACHOLAK, Amanda; BURLAGA, Natalia; KACZOREK, Ewa. Evaluating the effect of azole antifungal agents on the stress response and nanomechanical surface properties of ochrobactrum anthropi Aspcl2. 2. Molecules, v. 25, n. 15, p. 3348, 2020.
ROCHA, Ana Paula Santiago et al. Perfil epidemiológico das leveduroses sistêmicas em Unidades de Terapia Intensiva de hospitais públicos da cidade do Recife–PE, Brasil. Brazilian Journal of Health Review, v. 3, n. 6, p. 19098-19111, 2020.
ROKAS, Antonis. Evolution of the human pathogenic lifestyle in fungi. Nature Microbiology, v. 7, n. 5, p. 607-619, 2022
SAARI, Teijo I. et al. Effect of voriconazole and fluconazole on the pharmacokinetics of intravenous fentanyl. European journal of clinical pharmacology, v. 64, n. 1, p. 25-30, 2008.
SARAVOLATZ, Louis D.; JOHNSON, Leonard B.; KAUFFMAN, Carol A. Voriconazole: a new triazole antifungal agent. Clinical infectious diseases, v. 36, n. 5, p. 630-637, 2003.
SARI, Suat et al. Discovery of new azoles with potent activity against Candida spp. and Candida albicans biofilms through virtual screening. European journal of medicinal chemistry, v. 179, p. 634-648, 2019.
SCORZONI, Liliana et al. Current and promising pharmacotherapeutic options for candidiasis. Expert Opinion on Pharmacotherapy, v. 22, n. 7, p. 887-888, 2021.
SHAFIEI, Mohammad et al. History of the development of antifungal azoles: A review on structures, SAR, and mechanism of action. Bioorganic Chemistry, v. 104, p. 104240, 2020.
SILVA, Laura Nunes et al. Fungal infections in COVID-19-positive patients: a lack of optimal treatment options. Curr Top Med Chem, v. 20, n. 22, p. 1951-1957, 2020.
SILVA, Líllian OP; ALVES, Emanuele A.; NOGUEIRA, Joseli MR. Consequências do uso indiscriminado de antimicrobianos durante a pandemia de COVID-19. Brazilian Journal of Development, v. 8, n. 2, p. 10381-10397, 2022.
SINGH, Awadhesh Kumar et al. Mucormycosis in COVID-19: a systematic review of cases reported worldwide and in India. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, v. 15, n. 4, p. 102146, 2021.
TAVARES, Ramiro Moreira et al. Aspergilose e mucormicose–micoses sistêmicas de importância em COVID-19: Artigo de revisão. Research, Society and Development, v. 10, n. 7, p. e59410717101-e59410717101, 2021.
TERRA, Luciana et al. Mycoses and Antifungals: reviewing the basis of a current problem that still is a biotechnological target for marine products. Frontiers in Marine Science, v. 1, p. 12, 2014.
TORNIO, Aleksi et al. Clinical studies on drug–drug interactions involving metabolism and transport: methodology, pitfalls, and interpretation. Clinical Pharmacology & Therapeutics, v. 105, n. 6, p. 1345-1361, 2019.
ZHU, Yanmin et al. Oral fluconazole use in the first trimester and risk of congenital malformations: population based cohort study. bmj, v. 369, 2020.
ZUO, Cheng-zi et al. Effect of fluconazole on the pharmacokinetic properties of imrecoxib, a novel NSAID: a single-center, open-label, self-controlled study in healthy chinese male volunteers. Clinical therapeutics, v. 40, n. 8, p. 1347-1356, 2018.
