上海交通大学：《药理学 Pharmacology》课程教学资源（讲义课件）Aminoglycosides（氨基糖苷 类）and polymyxins 多粘菌素）Macrolides（大环内酯类）and other antibiotics

Aminoglycosides(氨基糖苷 类)and polymyxins多粘菌素) Macrolides（大环内酯类) and other antibiotics

Aminoglycosides（氨基糖苷 类）and polymyxins 多粘菌素） Macrolides（大环内酯类） and other antibiotics

Aminoglycosides(氨基糖苷 类) Tuberculosis,still severe infectious disease now 1882,Heinrich Hermann Robert Koch discovered M.tuberculosis(结核分枝杆菌) 1940's,Merck supported S.A.Waksman's lab, Rutgers university,NJ ·1940,actinomycin(放线菌素)，toxic ·1942,streptothricin(链丝菌素)，still toxic 1943,Albert Schatz,PhD student,entered lab

Aminoglycosides（氨基糖苷 类） • Tuberculosis, still severe infectious disease now • 1882, Heinrich Hermann Robert Koch discovered M. tuberculosis （结核分枝杆菌） • 1940’s, Merck supported S.A. Waksman’s lab, Rutgers university, NJ • 1940, actinomycin（放线菌素）, toxic • 1942, streptothricin （链丝菌素），still toxic • 1943, Albert Schatz, PhD student, entered lab

Aminoglycosides 1943.6 returned from army HO 0ct19,1943, OH streptomycin isolated HO… 一NH2 1944,Mayo clinic clinical trial HO HN-CH3 OH NH2 一NH2 1946,graduated and H2N patent left in Rutgers 1947,succeeded in Streptomycin(链霉素) TB treatment Law suit 1952,Nobel Prize to Waksman

Aminoglycosides 1943.6 returned from army Oct 19, 1943 ， streptomycin isolated 1944, Mayo clinic clinical trial 1946, graduated and patent left in Rutgers 1947, succeeded in TB treatment Law suit 1952, Nobel Prize to Waksman Streptomycin（链霉素）

30 人/10万 2的 结核 脑血管疾病 01 铂 癌 1QU 心血管疾病 50 10 191D 1920 1033 识HO 105A0 100 1970 1P80 年 本世纪三大流因及结核的死亡率变化

The Nobel Prize in Physiology or Medicine 1952 "for his discovery of streptomycin,the first antibiotic effective against tuberculosis" Selman Abraham Waksman

Individual aminoglycosides ·Streptomycin(链霉素) ·Gentamycin(庆大霉素) ·Amikacin(氨苄卡星) ·Tobramycin(妥布霉素) ·Netilmycin(奈替米星) ■

Individual aminoglycosides • Streptomycin（链霉素） • Gentamycin（庆大霉素） • Amikacin（氨苄卡星） • Tobramycin（妥布霉素） • Netilmycin（奈替米星） • …

Aminoglycosides Common characteristics: Potent effect on G bacteria,including Pseudomonas aeroginosa,Mycobacterium tuberculosis √Not absorbed orally Untoward effects:>5 days;high dose;elderly; renal insufficiency Ototoxicity(2%-10%):vertigo(眩晕)， ataxia(共济失调)，loss of banlance Nephrotoxicity (6%-10%) Neuromuscular blocking (co-administered with general analgesics or muscle relaxants)

Aminoglycosides Common characteristics:  Potent effect on G- bacteria, including Pseudomonas aeroginosa, Mycobacterium tuberculosis  Not absorbed orally  Untoward effects: >5 days; high dose; elderly; renal insufficiency • Ototoxicity （ 2 ％-10％）: vertigo（眩晕）, ataxia（共济失调）, loss of banlance • Nephrotoxicity （ 6 ％-10％） • Neuromuscular blocking (co-administered with general analgesics or muscle relaxants)

Toxicity of aminoglycodises ● Severe ototoxicity and nephrotoxicity. 18 of 21 actresses showing "qianshou guanyin"were caused deafness by aminoglycosides

Toxicity of aminoglycodises • Severe ototoxicity and nephrotoxicity. • 18 of 21 actresses showing “qianshou guanyin” were caused deafness by aminoglycosides

A B C 78 9 10 6 11 2 3 12 5 Auricle;middle ear;inner ear

Auricle; middle ear; inner ear

anterior canal 小囊 Nerve Utricle 球囊 Saccule posterior canal horzontal canal Cochlea 耳蜗 水平半规管

耳蜗 球囊 小囊 水平半规管