Tương Tác Dược Phẩm - Dược Động Học với Các Thuốc Kháng Viêm Không Steroid

Springer Science and Business Media LLC - Tập 27 - Trang 462-485 - 2012
Jacobus R. B. J. Brouwers1, Peter A. G. M. de Smet2
1Department of Pharmaceutical Pharmacology and Clinical Pharmacy, Groningen Institute for Drug Studies, State University, Groningen, The Netherlands
2Drug Information Centre, Royal Dutch Association for Advancement of Pharmacy, The Hague, The Netherlands

Tóm tắt

Các thuốc kháng viêm không steroid (NSAIDs) được kê đơn rất phổ biến, đặc biệt là trong dân số cao tuổi. Tại nhiều quốc gia, có hơn 10 loại NSAIDs khác nhau có sẵn. Vì các hợp chất pyrazole cũ như phenylbutazone, oxyphenbutazone và azapropazone dễ bị tương tác dược động học hơn, việc sử dụng các hợp chất này nên được tránh khi có thể. Các NSAIDs có tính acid tương tác với các nhựa liên kết acid mật, dẫn đến nồng độ NSAIDs trong máu giảm. Trong các báo cáo trước đây, đã đề xuất rằng sự hấp thu của NSAIDs bị ảnh hưởng bởi các thuốc kháng acid và sucralfate. Gần đây, người ta đã chỉ ra rằng có sự hấp thu chậm của các thuốc này, nhưng không có sự khác biệt trong phạm vi hấp thu. Chỉ có các salicylate là có sự tiết niệu gia tăng do các thuốc kháng acid, vốn làm tăng pH niệu đến giá trị >7. Các chất đối kháng thụ thể histamine H2 có thể được kết hợp an toàn với NSAIDs. Việc sử dụng đồng thời probenecid làm tăng nồng độ NSAIDs trong máu, do đó có thể mong đợi hiệu ứng chống viêm mạnh hơn khi kết hợp hai loại thuốc này. Quan trọng hơn, NSAIDs có thể gây ra các tương tác dược phẩm - dược động học với các thuốc khác. Như có thể dự đoán, các tương tác với các thuốc có chỉ số trị liệu hẹp nhất có khả năng có ý nghĩa lâm sàng cao nhất. Ví dụ, lithium, methotrexate liều trung bình đến cao và, ở mức độ ít hơn, ciclosporin có thể bị ảnh hưởng bởi việc sử dụng đồng thời NSAID. Aspirin (acid acetylsalicylic) và/hoặc các pyrazole tương tác với các thuốc chống đông máu đường uống, các tác nhân hạ đường huyết đường uống và các thuốc chống co giật phenytoin và acid valproic (natri valproate). Sự gia tăng nồng độ máu của các tác nhân này có thể gây nguy hiểm. Tương tự, NSAIDs tương tác với digoxin. Tương tác này có khả năng xảy ra cao nhất ở người cao tuổi, trẻ sơ sinh hoặc bệnh nhân suy thận. Indomethacin có thể ảnh hưởng đến nồng độ máu của aminoglycosides ở trẻ sơ sinh. Đáng tiếc là, hiệu ứng này có vẻ không thể đoán trước, vì vậy không thể đưa ra những khuyến cáo điều trị thực tiễn. Khi NSAIDs được kết hợp với salicylates hoặc diflunisal, nồng độ máu của salicylate hoặc diflunisal có thể tăng. Tuy nhiên, ý nghĩa lâm sàng của sự gia tăng nồng độ thuốc này dường như ít quan trọng hơn. Xuất huyết tiêu hóa do NSAIDs thường nguy hiểm nhất khi kết quả từ một tương tác dược động học/dược lực học hỗn hợp; tuy nhiên, bệnh nhân cũng có nguy cơ khi chỉ có các tương tác dược lực học xảy ra.

Từ khóa

#NSAIDs #Tương tác thuốc #Dược động học #Dược lực học #Bệnh nhân cao tuổi

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