Tülün ÖZTÜRK, Tuğba GÜRPINAR, Canet İNCİR BALABAN, Yeşim TUNÇOK

Potential Interactions between Increased Cytokines in COVID-19 and Drugs Used to Treat COVID-19

During COVID-19 infection, virus and host cell interactions lead to the acute production of very strong immune mediators. The clinical status caused by damage throughout the body is mostly due to excessive pro-inflammatory cytokine production from virus-induced macrophages and granulocytes. Under infectious and inflammatory conditions, clinical and experimental studies have demonstrated that hepatic and extrahepatic cytochrome P450 (CYP) enzymes and carrier proteins responsible for drug metabolism are specifically regulated by many cytokines. Downregulation of these enzymes by cytokines can cause an elevation in plasma drug levels and/or lead to adverse drug reactions and/or toxicity. Based on the knowledge of cytokine-drug interactions occurring in the infection and inflammation stage, the aim of this review was to ascertain the influence of uncontrolled cytokine release on the metabolism of drugs used alone or in combination to treat COVID-19 patients and predict drug-drug interactions causing adverse effects.

COVİD-19 da Sitokinler ve COVİD- 19 Tedavisinde Kullanılan İlaçlar Arasında Potansiyel İlaç Etkileşimleri

COVID-19 enfeksiyonu sırasında virus ve konakçı hücre etkileşimleri çok güçlü immun mediyatörlerin akut üretimine yol açmaktadır. Ağır klinik durum çoğunlukla virüsün indüklediği makrofaj ve granülositlerden aşırı inflammatuar sitokin üretimine bağlıdır. Enfeksiyöz ve inflammatuar koşullar altında, klinik ve deneysel çalışmalar göstermiştir ki, ilaç metabolizmasından sorumlu olan karaciğer ve karaciğer dışı sitokrom P450 (CYP) enzimleri ve taşıyıcı proteinler pek çok sitokinler tarafından spesifik olarak regüle edilmektedirler. Sitokinler tarafından bu enzimlerin downregülasyonu, plazma ilaç düzeylerinde yükselmeye neden olabilir ve/veya advers ilaç reaksiyonlarına ve/veya toksisiteye yol açabilir. İnfeksiyon ve inflammasyon koşullarında oluşan sitokin-ilaç etkileşimleri bilgilerimiz temelinde, bu derlemenin amacı, COVID-19 hastalarını tedavi etmek için tek başına veya kombinasyonla kullanılan ilaçların metabolizmaları üzerine kontrolsüz sitokin salınımının etkisini araştırmak ve advers ilaç etkilerine neden olabilecek ilaç- ilaç etkileşimlerini öngörmektir.

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