Section 3 Macrolides Lincomycins vancomycins Yun-Bi Lu, PhD 卢韵碧 Dept of Pharmacology, School of Medicine, Zhejiang University yunbi@zju.edu.cn
Macrolides, Lincomycins &Vancomycins Section 3 Yun-Bi Lu, PhD 卢韵碧 Dept. of Pharmacology, School of Medicine, Zhejiang University yunbi@zju.edu.cn
Part A Macrolides Erythromycin(红零素 · Clarithromycin(克拉零亲) Azithromycin(阿奇霉素) Telithromycin(泰利零亲
• Erythromycin (红霉素) • Clarithromycin (克拉霉素) • Azithromycin (阿奇霉素) • Telithromycin(泰利霉素) Part A Macrolides
CH H3C OCH. H3C、CH3 --CH CH H3C 00—cH CH H2C、OH OH H2C、CH C OCH3 OH CH3 CH CH OH H3C 0o—cH O CLARITHROMYCIN CH 14 member rings 2 CH CH O H3CAN CH3 OCH CH CH H3C.HO OH -CHa H3C CH OH HO CH H3C CH ERYTHROMYCIN CH2 CH OCH 14 member rings CH CH CH AZITHROMYCIN 15 member rings
14 member rings 15 member rings 14 member rings
General properties of Macrolides 1. Antimicrobial spectrum Gt organisms G- cocci: Streptococcus pyogenes and pneumoniae Mycoplasma pneumoniae(肺支原体)and Legionnella(军团菌)etc 2. Antimicrobial activity: bactericidal and bacteriostatic depending on the concentration · more active at alkaline
1. Antimicrobial spectrum： • G+ organisms • G- cocci: Streptococcus pyogenes and pneumoniae • Mycoplasma pneumoniae(肺支原体) and Legionnella (军团菌)etc. 2. Antimicrobial activity: • bactericidal and bacteriostatic, depending on the concentration. • more active at alkaline General properties of Macrolides
3. Mechanism of action: 50S subun peptide macrolide bond 50s subunit A C cC U U A CGC G XXXXXXAUGCGCGGAUCC/ XXXXXXAUGCGCGGAUCCCCCACCUGA codon 1 codon 2 codon 3 codon 4 codon 5 codon 6 codon 7 (SER) (f-METL(ARG) (GLY) (SER) (PRO) (THR) (Stop) 30s start) 30s subunit macrolide subunit mRN
3. Mechanism of action: subunit macrolide
4. Mechanism of resistance: modification of the ribosomal binding site production of esterase that hydrolyze macrolides reduced permeability of cell membrane or active efflux system is involved Cross-resistance is complete between erythromycin and the other macrolides
4. Mechanism of resistance: • modification of the ribosomal binding site • production of esterase that hydrolyze macrolides. • reduced permeability of cell membrane or active efflux system is involved. • Cross-resistance is complete between erythromycin and the other macrolides
General properties of Macrolides 4. ADME 1)Absorption: Stearate and ester of erythromycin are fairly acid-resistant and somewhat batter absorbed Food interferes with absorption
4. ADME 1) Absorption: Stearate and ester of erythromycin are fairly acid-resistant and somewhat batter absorbed. Food interferes with absorption. General properties of Macrolides
General properties of Macrolides 4. ADME 2)Distribution: does not cross BBB. 3 Elimination: it is concentrated in the liver, where some is unactive while some is excreted in active form in the bile
4. ADME 2) Distribution: does not cross BBB. 3) Elimination: it is concentrated in the liver, where some is unactived, while some is excreted in active form in the bile. General properties of Macrolides
General properties of Macrolides 5. Clinical Uses. 1) Mycoplasma(支原体) infections 2) Legionnaire's disease(军因菌病) 3) Chlamydia infections(衣原体感染) 4) Streptococcus(链赇黄) infections 5) Diphtheria(台赛) chincough(百目咳) 6) toxoplasmosis(子形虫病)
5.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) Streptococcus (链球菌) infections. 5) Diphtheria (白喉), chincough(百日咳). 6) toxoplasmosis(弓形虫病). General properties of Macrolides
General properties of Macrolides 6. Adverse response: 1)G Effects: nausea, vomiting, abdominal cramps(痉享)… 2)Liver Toxicity: Cholestatic hepatitis (胆汁淤积性肝炎) 3)Cardiotoxic effects 4)Auditory impairment (ototoxicity) Hypersensitivity reactions Superinfections
6.Adverse response: 1) GI Effects: nausea, vomiting, abdominal cramps(痉挛)… 2) Liver Toxicity: Cholestatic hepatitis (胆汁淤积性肝炎). 3) Cardiotoxic effects 4) Auditory impairment (Ototoxicity) Hypersensitivity reactions Superinfections General properties of Macrolides