32.下列何者會增加aminoglycoside相關急性腎衰竭的風險？①慢性腎臟病 ②較高的峰濃度 ③併用 vancomycin ④once daily dosing
(A)①②
(B)①③
(C)②④
(D)③④

給跟我一樣覺得aminoglycoside的腎毒性是Concentration Dependent 所以選C的

的確從機轉上腎毒性與濃度相關，但毒性的產生是aminoglycoside留在腎小管細胞造成的，如以下截取段落所示，有興趣的可以點連結去讀全文。

ㅤㅤ

When the concentration of aminoglycoside in endosomal structures exceeds an undetermined threshold, their membrane is disrupted and their content, along with the drug, is poured into the cytosol.55., 56. Cytosolic gentamicin then acts on mitochondria directly and indirectly,57., 58. and thus activates the intrinsic pathway of apoptosis, interrupts the respiratory chain, impairs ATP production,58., 59. and produces oxidative stress by increasing superoxide anions and hydroxyl radicals,60., 61. which further contributes to cell death. The indirect mitochondrial effect is mediated by increasing Bax levels⁶² through the inhibition of its proteosomal degradation.

ㅤㅤ

Ref: https://www.sciencedirect.com/science/article/pii/S0085253815546760

ㅤㅤ

According to the information on the current page, aminoglycoside-related nephrotoxicity is indeed concentration-dependent. The page explains that nephrotoxicity is a significant side effect of aminoglycoside antibiotics, particularly gentamicin, and occurs despite careful patient monitoring. The incidence of nephrotoxicity ranges from 10–25% of treatments. The toxicity is primarily due to the accumulation of the drug in renal tissues, especially when high concentrations are reached. The page also discusses various mechanisms of tubular cell death and sub-lethal alterations in tubular reabsorption, which are influenced by the concentration of the drug. Thus, the severity of nephrotoxic effects is related to the drug concentration in the kidneys.

感謝Copilot的整理

ㅤㅤ

ㅤㅤ

但從另一篇文章我們知道，腎小管細胞是會飽和的，所以造成的傷害不會隨著藥物濃度提高而無上限跟著提高。
所以，Once daily dosing 雖然讓藥物濃度一下衝上去但相比於Conventional dosing讓細胞一直「泡」在Aminoglycoside中，減少給藥次數反而能降低腎毒性。

According to the information on the current page, aminoglycoside-related nephrotoxicity is indeed concentration-dependent. Here are the key points:

• Concentration-Dependent Toxicity: The toxicity of aminoglycosides is related to their local concentration within the kidney, particularly in the lysosomes of proximal tubular cells.
• Lysosomal Storage: Aminoglycosides are stored in lysosomes, and the extent of lysosomal alterations correlates with their nephrotoxic potential.
• Saturation of Uptake: The uptake of aminoglycosides by kidney tubular cells is saturable, meaning that at high concentrations, not all of the drug passing through the lumen will be reabsorbed.
• Once-Daily Dosing: Administering aminoglycosides as a single daily dose creates a high peak level in serum, which is less toxic than multiple daily doses due to the saturable nature of renal uptake. This has led to the clinical adoption of once-daily dosing regimens for aminoglycosides.

These points suggest that the nephrotoxicity of aminoglycosides can be mitigated by controlling the concentration and dosing schedule.

再次感謝Copilot的整理

Ref：https://www.ncbi.nlm.nih.gov/pmc/articles/PMC89104/