Tương tác thuốc dược lý học với các tác nhân kháng khuẩn

Springer Science and Business Media LLC - Tập 25 - Trang 450-482 - 2012
J. Gregory Gillum1, Debra S. Israel1, Ron E. Polk1
1School of Pharmacy, Virginia Commonwealth University, Medical College of Virginia, Richmond, USA

Tóm tắt

Khi các loại thuốc kháng khuẩn mới được phát triển và những ứng dụng mới cho thuốc cũ được tìm thấy, các tương tác thuốc dược lý học với các tác nhân kháng khuẩn ngày càng trở nên phổ biến. Các dẫn xuất macrolide, fluoroquinolone, rifamycin, azole và các tác nhân khác có thể tương tác tiêu cực với các loại thuốc thường dùng, thường thông qua việc làm thay đổi quá trình trao đổi chất tại gan của chúng. Các cơ chế mà các tác nhân kháng khuẩn làm thay đổi quá trình sinh chuyển hóa của các thuốc khác ngày càng được hiểu rõ là do ức chế hoặc kích thích các enzym cytochrome P450 cụ thể. Các dẫn xuất macrolide ức chế cytochrome P450IIIA4 (CYP3A4), đây dường như là enzym chuyển hóa phổ biến nhất trong gan của con người và tham gia vào quá trình chuyển hóa của nhiều loại thuốc, bao gồm cyclosporin, warfarin và terfenadine. Một số quinolone ức chế CYP1A2 ưu tiên, enzym này có phần trách nhiệm trong quá trình chuyển hóa methylxanthine. Các azole dường như là những chất ức chế phổ rộng các cytochrome P450. Trong mỗi loại kháng sinh này, có một thứ tự về sức mạnh ức chế đối với các enzym cytochrome P450 cụ thể. Trái lại, rifampicin (rifampin) và rifabutin kích thích một số cytochromes P450, bao gồm CYP3A4, do đó có thể làm tăng quá trình chuyển hóa của nhiều thuốc khác. Bằng cách sử dụng các chế phẩm enzym của người trong ống nghiệm, ngày càng có thể dự đoán những loại kháng sinh nào sẽ ảnh hưởng tiêu cực đến quá trình chuyển hóa của các thuốc khác. Thêm vào đó, sự biến đổi giữa các bệnh nhân về tần suất tương tác có thể liên quan đến sự khác biệt trong hoạt động của các enzym này. Mặc dù các cơ chế và phạm vi của các tương tác này đang được xác định rõ, thách thức còn lại là làm thế nào để thông báo cho bác sĩ lâm sàng một cách tốt nhất để ngăn ngừa những hậu quả không mong muốn của các tương tác.

Từ khóa

#tương tác thuốc #kháng khuẩn #cytochrome P450 #dược lý học #thuốc kháng sinh

Tài liệu tham khảo

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