General properties of Macrolides 4. Mechanism of action(bind to P site) 1. Blocking translocation of peptidyl tRNA from A site to P site (B 位,14) 2 Preventing the peptidyl transfer(转肽,16C) 3. Inhibiting the formation of functional 70s ribosome 4. Bind to L27 and L22 protein to cause dissociation of peptidyl tRNA from the ribosome
4. Mechanism of action (bind to P site): General properties of Macrolides 1. Blocking translocation of peptidyl tRNAfrom A site to P site (移 位, 14) 2. Preventing the peptidyl transfer (转肽, 16C) 3. Inhibiting the formation of functional 70s ribosome 4. Bind to L27 and L22 protein to cause dissociation of peptidyltRNA from the ribosome
General properties of macrolides 5 ADME of Macrolides. (Absorption Erythromycin is destroyed by stomach acid and must be administrated with enteric coating Stearates(硬脂酸) and ester(酯化) are fairly acid- resistant and somewhat better absorbed Clarithromycin and azithromycin are stable to acid Food interferes with absorption(except Clarithromycin)
5. ADME of Macrolides: (1)Absorption: • Erythromycin is destroyed by stomach acid and must be administrated with enteric coating. • Stearates (硬脂酸) and ester (酯化) are fairly acidresistant and somewhat better absorbed. • Clarithromycin and Azithromycin are stable to acid. • Food interferes with absorption (except Clarithromycin). General properties of macrolides
General properties of macrolides 5. ADME of macrolides (2 Distribution: Erythromycin diffuses readily into most tissues, including prostatic fluid and placenta, BBB impenetrable. (3)Metabolism and Elimination: most metabolized in the liver. excreted in the bile clarithromycin and its metabolite excreted in urine
5. ADME of macrolides: (2)Distribution: Erythromycin diffuses readily into most tissues, including prostatic fluid and placenta, BBB impenetrable. (3) Metabolism and Elimination: most metabolized in the liver, excreted in the bile； clarithromycin and its metabolite excreted in urine. General properties of macrolides
General properties of macrolides 6. Clinical Uses (1) Mycoplasma(支原体) infections (2) Legionnaire's disease(军团菌病) (3) Chlamydia infections(衣原体感染) (4) Diphtheria(白喉) 5) Pertussis(百日咳) (6) Streptococcus(链球菌), staphylococcus (金葡菌) infections
6.Clinical Uses: (1) Mycoplasma（支原体） infections (2) Legionnaire’s disease（军团菌病） (3) Chlamydia infections（衣原体感染） (4) Diphtheria（白喉） (5) Pertussis （百日咳） (6) Streptococcus （链球菌）, staphylococous （金葡菌） infections General properties of macrolides
General properties of macrolides 7. Adverse response: (1Gl effects: nausea, vomiting, abdominal cramps, etc. (2)Liver toxicity: Cholestatic hepatitis (胆汁淤积性肝炎) (3)Auditory impairment (4 Allergic reaction (5 Superinfections
7.Adverse response: (1) GI effects: nausea, vomiting, abdominal cramps, etc. (2) Liver toxicity: Cholestatic hepatitis （胆汁淤积性肝炎）. (3) Auditory impairment. (4) Allergic reaction (5) Superinfections General properties of macrolides