Aminoglycoside胺基配糖體抗生素

• 主條目:Taiwanese Antibacterial antibiotics classification抗菌抗生素分類
• Aminoglycoside, 結構和Aminoglycoside不同的aminocyclitol在教科書中都列在本章

來源

~mycin	~micin
Streptomyces	Micromonospora

例子

• 口服 and 局部
  • neomycin: most nephrotoxic, ototoxic. Pseudomonas and Streptococcus are resistant
  • paramomycin
  • kanamycin: most ototoxic. Pseudomonas and Streptococcus are resistant 抗生素的抗菌譜特色
• 注射
  • amikacin most ototoxic. (半合成自kanamycin A, 無論是pottency或是spectrum皆優於之): gentamicin-resistant G(-),tobramycin-resistant G(-), multidrug-resistant Mycobacterium tuberculosis including streptomycin-resistant one often susceptable to it. Pseudomonas is susceptable to it.
  • tobramycin(半合成自kanamycin B): most nephrotoxicity, spectrum and PK are similar to gentamicin, 用於長期投與
  • gentamicin: most nephrotoxicity, vestibulotoxic, active to G(+)
    • enterococcus resistant to it for their enzyme, thus we can use streptomycin to treat it.
  • netilmicin:spectrum is the same to that of gentamicin and tobramycin, can treat gentamicin-resistant G(-) and tobramycin-resistant G(-).
  • sisomicin: similar to gentamicin
  • streptomycin: most vestibulotoxic, use as second-line agent for treatment of turberculosis
  • capreomycin:second-line agent of tuberculosis,amikacin-resistant
  • spectinomycin(IM):a Aminocyclital antibiotic, no Cross-resistance with other aminoglycosides, alternative treatment for drug-resistant gonorrhea(淋病) or gonorrhea in penicillin-allergic patients.
• gentamicin, kanamycin, and neomycin can treat G(+)
• 交叉抗藥性:
  • amikacin(半合成自kanamycin A)和kanamycin
  • kanamycin和neomycin

機轉

• 抑制initiation(所以殺菌)
• 和elongation by binding to 30s(irreversible)
• 造成DNA的誤讀，但是spectinomycin(IM)不會

治療學

• aminoglycoside is widely against G(-), especially in bacteremia and sepsis
  • such as enteric bacteria
  • 和Beta-lactam antibiotics一起使用可以增強對G(+)的效用
• because the process aminoglycosides across cell membrane into the cytoplasm is a oxygen-dependant secondary active transportation, it can be used to kill G(-) aerobes only, anaerobes are not susceptable .
• the transmembrane electrochemical gradient supplies the energy for this process, and transport is coupled to a proton pump.
• low extracellular pH and anaerobic condition inhibit transport by reducing gredient.
• cell wall-active drug:penicillins, vancomycin, when used with Aminoglycosides, transport of aminoglycosides into cell is enhanced.
• once daily dosing 是因為後抗生素效應
• in the infection of Streptococcal, Staphylococcal, and enterococcal Endocarditis, thrice-daily administration is still recommended.
  • 和Beta-lactam antibiotics一起使用可以增強對G(+)的效用
  • gentamicin is not active to Streptococcal, and enterococcal
  • when treat infection of Staphylococcal, Gentamicin often be used with vancomycin and penicillins.
• some of the administered aminoglycosides can pass BBB only when active inflammation presents.
  • for higher conc. , intrathecal and intraventricular injection is needed.
  • however, this therapy has benn substituted by third generation cephalosporin.
• cannot be used as single agent to treat pneumonia for poor penatration

配伍

• cell wall-active drug:penicillins, vancomycin, when used with Aminoglycosides, transport of aminoglycosides into cell is enhanced.
• 和Beta-lactam antibiotics一起使用可以增強對G(+)的效用
• Aminoglycoside are in combination with vancomycin or a penicillins for endocarditis, and for treatment of tuberculosis
  • gentamicin(aminoglycoside)+vancomycin is the alternative of enterococcal endocarditis
• Streptomycin plus Penicillins is effective for
  • enterococcal endocarditis
  • virdans streptococcal endocarditis
• third-generation cephalosporins
  • Empirical therapy of sepsis of unknown cause in both the immunocompetent and the immunocompromised patient.
  • in neutropenic, febrile immunocompromised patients, third-generation cephalosporins are often used in combination with an aminoglycosides.
• Imipenem and Meropenem with or without Aminoglycoside can treat febrile neutropenic patients(發燒型嗜中性白血球低下症)
• oral tetracyclines often coadministrate with Aminoglycoside to treat plague(鼠疫), tularemia(兔熱病), and brucellosis(布氏桿菌症)
  • 1g/d (15mg/kg/d for children) streptomycin is given IM in combination with an oral tetracycline.

毒性

• 腎毒性和耳毒性
  • 腎毒性:reversible
  • 耳毒性:irreversible
• if used in pregnancy, it may cause deafness in newborn.
• toxicity is both concentration-dependent and time-dependent
• if the trough conc.(波谷濃度) is above 2μg/ml , toxicity may happen.
• toxicity is less possible to happen in Once daily dosing
  • if the therapy is longer than 2~3 days, serum conc. need be routinely checked, depends on renal function.
• If streptomycin was used over 6 months in TB, the toxicity may happen
• if used with loop diuretics may potentiate nephrotoxicity.
• 高劑量的時候可能會像curare一樣產生作用:give calcium gluconate (give promptly) or neostigmine 解毒

重點

• aminoglycoside is widely against G(-), especially in bacteremia and sepsis
  • such as enteric bacteria
  • 和Beta-lactam antibiotics一起使用可以增強對G(+)的效用
• 口服 and 局部
  • neomycin: most nephrotoxicity. Pseudomonas and Streptococcus are resistant
  • paramomycin
  • kanamycin: Pseudomonas and Streptococcus are resistant 抗生素的抗菌譜特色*once daily dosing 是因為後抗生素效應
• in the infection of Streptococcal, Staphylococcal, and enterococcal Endocarditis, thrice-daily administration is still recommended.
  • 和Beta-lactam antibiotics一起使用可以增強對G(+)的效用
  • gentamicin is not active to Streptococcal, and enterococcal
  • when treat infection of Staphylococcal, Gentamicin often be used with vancomycin and penicillins.
• gentamicin: most nephrotoxicity, vestibulotoxic, active to G(+)
  • enterococcus resistant to it for their enzyme, thus we can use streptomycin to treat it.
• 口服 and 局部
  • neomycin: most nephrotoxicity. Pseudomonas and Streptococcus are resistant
  • paramomycin
  • kanamycin: Pseudomonas and Streptococcus are resistant 抗生素的抗菌譜特色
• Aminoglycoside are in combination with vancomycin or a penicillins for endocarditis, and for treatment of tuberculosis
  • gentamicin(aminoglycoside)+vancomycin is the alternative of enterococcal endocarditis
• Streptomycin plus Penicillins is effective for
  • enterococcal endocarditis
  • virdans streptococcal endocarditis
• third-generation cephalosporins
  • Empirical therapy of sepsis of unknown cause in both the immunocompetent and the immunocompromised patient.
  • in neutropenic, febrile immunocompromised patients, third-generation cephalosporins are often used in combination with an aminoglycosides.
• Imipenem and Meropenem with or without Aminoglycoside can treat febrile neutropenic patients(發燒型嗜中性白血球低下症)

延伸學習

• 胺糖
• aminoglycoside
• Aminocyclital antibiotic

參考資料

• basic2007
• 藥理學(白老師)

藥品學名	非糖	糖(胺糖)	其他
neomycin B	2-deoxystreptamine	*neosamine C(2,6-diamino-2,6-dideoxy-D-glucose)(6-amino-6-deoxy-D-glucosamine)和2-deoxystreptamine合稱neamine、 D-ribose、neosamine B合稱neobiosamine B	四個環、和paramomycin I差在D-glucosamine
neomycin C	2-deoxystreptamine	*neosamine C和2-deoxystreptamine合稱neamine、 D-ribose、neosamine C合稱neobiosamine C	四個環、和paramomycin II差在D-glucosamine
paramomycin I	2-deoxystreptamine	*D-glucosamine和2-deoxystreptamine合稱paromamine、 D-ribose、neosamine B	四個環、和Neomycin B差在neosamine C
paramomycin II	2-deoxystreptamine	*D-glucosamine(2-amino-2-deoxy-D-glucose)和2-deoxystreptamine合稱paromamine、 D-ribose、neosamine C	四個環、和Neomycin C差在neosamine C
kanamycin	2-deoxystreptamine	kanosamine(3-amino-3-deoxy-D-glucose)	三個環
kanamycin A	2-deoxystreptamine	kanosamine、6-amino-6-deoxy-D-glucose	三個環
kanamycin B	2-deoxystreptamine	kanosamine、2,6-diamino-2,6-dideoxy-D-glucose(6-amino-6-deoxy-D-glucosamine)(neosamine C)	三個環
kanamycin C	2-deoxystreptamine	kanosamine、2-amino-2-deoxy-D-glucose(D-glucosamine)	三個環
amikacin	L-AHBA2-deoxystreptamine	kanosamine、6-amino-6-deoxy-D-glucose(kanamycin A der.)	三個環
tobramycin	2-deoxystreptamine	kanosamine、kanamycin B der.	三個環
gentamicin	2-deoxystreptamine	garosamine	三個環
netilmicin	2-deoxystreptamine	garosamine、含雙鍵的胺糖	三個環
sisomicin	2-deoxystreptamine	garosamine、含雙鍵的胺糖	三個環
streptomycin	streptidine	streptobiosamine= L-streptose + N-methyl-L-glucosamine	三個環
spectinomycin	spectinamine		三個環