chapter 38 macrolides, lincomycins and polymycins
DESCRIPTION
Chapter 38 Macrolides, Lincomycins and Polymycins. 大环内酯类药物. 14 元大环内酯类 :红霉素、 罗红霉素、克拉霉素 、地红霉素 15 元大环内酯类 : 阿奇霉素 16 元大环内酯类 :螺旋霉素、乙酰螺旋霉素、麦迪霉素、麦白霉素、罗他霉素、柱晶白霉素、交沙霉素、米欧卡霉素. Macrolides. First generation : 1950’s—erythromycin Second generation : 1970’s—claithromycin azithromycin - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: Chapter 38 Macrolides, Lincomycins and Polymycins](https://reader036.vdocuments.pub/reader036/viewer/2022062305/568149df550346895db70573/html5/thumbnails/1.jpg)
Chapter 38
Macrolides, Lincomycins
and Polymycins
![Page 2: Chapter 38 Macrolides, Lincomycins and Polymycins](https://reader036.vdocuments.pub/reader036/viewer/2022062305/568149df550346895db70573/html5/thumbnails/2.jpg)
大环内酯类药物 14元大环内酯类:红霉素、罗红霉素、克拉霉素、地红霉素
15元大环内酯类:阿奇霉素 16元大环内酯类:螺旋霉素、乙酰螺旋霉素、麦迪霉素、麦白霉素、罗他霉素、柱晶白霉素、交沙霉素、米欧卡霉素
![Page 3: Chapter 38 Macrolides, Lincomycins and Polymycins](https://reader036.vdocuments.pub/reader036/viewer/2022062305/568149df550346895db70573/html5/thumbnails/3.jpg)
Macrolides
First generation : 1950’s—erythromycin Second generation : 1970’s—claithromycin
azithromycin Third generation :
![Page 4: Chapter 38 Macrolides, Lincomycins and Polymycins](https://reader036.vdocuments.pub/reader036/viewer/2022062305/568149df550346895db70573/html5/thumbnails/4.jpg)
Common properties of Macrolides
![Page 5: Chapter 38 Macrolides, Lincomycins and Polymycins](https://reader036.vdocuments.pub/reader036/viewer/2022062305/568149df550346895db70573/html5/thumbnails/5.jpg)
Antibacterial activity First generation
Most G+ organisms: pneumococci, streptococci, staphylococci , diphtheriae etc
Part G- organisms:legionella (军团菌) ,bacillus pertussis( 百日咳 ), brucella( 布氏 ) etc
Others: mycoplasma( 支原体 ), chlamydia trachomatis( 沙眼衣原体 ), rickettsia( 立克次体 ), spirochete ,anaerobes etc.
Second generation More active on G- organisms
![Page 6: Chapter 38 Macrolides, Lincomycins and Polymycins](https://reader036.vdocuments.pub/reader036/viewer/2022062305/568149df550346895db70573/html5/thumbnails/6.jpg)
Mechanism of action Target
50s ribosomal RNA Mechanism
inhibition of translocation of mRNA
![Page 7: Chapter 38 Macrolides, Lincomycins and Polymycins](https://reader036.vdocuments.pub/reader036/viewer/2022062305/568149df550346895db70573/html5/thumbnails/7.jpg)
![Page 8: Chapter 38 Macrolides, Lincomycins and Polymycins](https://reader036.vdocuments.pub/reader036/viewer/2022062305/568149df550346895db70573/html5/thumbnails/8.jpg)
![Page 9: Chapter 38 Macrolides, Lincomycins and Polymycins](https://reader036.vdocuments.pub/reader036/viewer/2022062305/568149df550346895db70573/html5/thumbnails/9.jpg)
Mechanism of resistance
Production of inactivating enzymes Modification of the ribosomal binding site Active efflux system MLSR
![Page 10: Chapter 38 Macrolides, Lincomycins and Polymycins](https://reader036.vdocuments.pub/reader036/viewer/2022062305/568149df550346895db70573/html5/thumbnails/10.jpg)
Pharmokinetics
Absorption Erythromycin: not stable at acid pH New macrolides: stable po
Distribution Metabolism:
Erythromycin&clarithromycin: in liver Excretion
Erythromycin& azithromycin: bile Clarithromycin: kidney
![Page 11: Chapter 38 Macrolides, Lincomycins and Polymycins](https://reader036.vdocuments.pub/reader036/viewer/2022062305/568149df550346895db70573/html5/thumbnails/11.jpg)
Commomly used macrolides
![Page 12: Chapter 38 Macrolides, Lincomycins and Polymycins](https://reader036.vdocuments.pub/reader036/viewer/2022062305/568149df550346895db70573/html5/thumbnails/12.jpg)
Erythromycin
Antimicrobial activity Gram-positive organisms: pneumococci, stre
ptococci, staphylococci , diphtheriae etc Gram-negative organisms:legionella (军团菌) ,
bacillus pertussis( 百日咳 ), brucella( 布氏 ) ,
meningococci, diplococcus gonorrhoeae etc Others: mycoplasma( 支原体 ), chlamydia trach
omatis( 沙眼衣原体 ), rickettsia( 立克次体 ), spirochete ,anaerobes etc.
![Page 13: Chapter 38 Macrolides, Lincomycins and Polymycins](https://reader036.vdocuments.pub/reader036/viewer/2022062305/568149df550346895db70573/html5/thumbnails/13.jpg)
Erythromycin
Clinical uses As penicillin substitute in penicillin-allergic or
resistant patients with infections caused by staphylococci, streptococci and pneumococci
Pertussis , diphtheriae Legionella and mycoplasma pneumonia H.p infection
![Page 14: Chapter 38 Macrolides, Lincomycins and Polymycins](https://reader036.vdocuments.pub/reader036/viewer/2022062305/568149df550346895db70573/html5/thumbnails/14.jpg)
Erythromycin
Adverse reactions Gastrointestinal effects Liver toxicity Cardiotoxicity
![Page 15: Chapter 38 Macrolides, Lincomycins and Polymycins](https://reader036.vdocuments.pub/reader036/viewer/2022062305/568149df550346895db70573/html5/thumbnails/15.jpg)
Erythromycin Erythromycin lactobionate( 乳糖酸红霉素) erythromycin estolate (无味红霉素 )
erythromycin stearate( 硬脂酸红霉素) erythromycin ethylsuccinate (琥乙红霉素, 利君沙)
![Page 16: Chapter 38 Macrolides, Lincomycins and Polymycins](https://reader036.vdocuments.pub/reader036/viewer/2022062305/568149df550346895db70573/html5/thumbnails/16.jpg)
New macrolides antibiotics Advantage :
Broader spectrum, higher activity Orally effective High blood concentration Longer t 1/2
Less toxicity Mainly used in respiratory tract infection
![Page 17: Chapter 38 Macrolides, Lincomycins and Polymycins](https://reader036.vdocuments.pub/reader036/viewer/2022062305/568149df550346895db70573/html5/thumbnails/17.jpg)
Clarithromycin (甲红霉素 , 克拉霉素)
Has the strongest activity on Gram-positive bacteria, legionella pneumophila, chlamydia pneumoniae and H.p
Good pharmacokinetic property Low toxicity
![Page 18: Chapter 38 Macrolides, Lincomycins and Polymycins](https://reader036.vdocuments.pub/reader036/viewer/2022062305/568149df550346895db70573/html5/thumbnails/18.jpg)
Azithromycin ( 阿齐霉素 , 丽珠奇乐)
Has the strongest activity against mycoplasma pneumoniae (肺炎支原体)
More effective on Gram-negative bacteria Well tolerated T1/2 :35~48h once daily Mainly used in respitory tract infection
![Page 19: Chapter 38 Macrolides, Lincomycins and Polymycins](https://reader036.vdocuments.pub/reader036/viewer/2022062305/568149df550346895db70573/html5/thumbnails/19.jpg)
Roxithromycin (罗红霉素,严迪) 1987 France The highest blood concentration F 72%~85% Respiratory tract infection and soft tissue
infection Low adverse effects
![Page 20: Chapter 38 Macrolides, Lincomycins and Polymycins](https://reader036.vdocuments.pub/reader036/viewer/2022062305/568149df550346895db70573/html5/thumbnails/20.jpg)
Lincomycin and Clindamycin Antimicrobial activity
Gram-positive organisms Bacteroide fragilis and other anaerobes
Mechanism Binding to 50s ribosome subunit and inhibiting
protein synthesis Pharmacokinetics
Absorbed well Penetrate well into most tissues including bone
![Page 21: Chapter 38 Macrolides, Lincomycins and Polymycins](https://reader036.vdocuments.pub/reader036/viewer/2022062305/568149df550346895db70573/html5/thumbnails/21.jpg)
Clindaycin
Clinical uses Severe anaerobic infection Acute or chronical suppurative osteomylitis , arthrit
is caused by susceptive organisms especially Staphylococci aureus
Adverse reactions Gastrointestinal effects: severe diarrhea and pseud
omembranous enterocolitis caused by Clostridium difficile :vancomycin & metronidazole
Other :Impaired liver function , neutropenia
![Page 22: Chapter 38 Macrolides, Lincomycins and Polymycins](https://reader036.vdocuments.pub/reader036/viewer/2022062305/568149df550346895db70573/html5/thumbnails/22.jpg)
Polypeptide antibiotics
Vancomycin & TeicoplaninPolymyxinsbactitracin
![Page 23: Chapter 38 Macrolides, Lincomycins and Polymycins](https://reader036.vdocuments.pub/reader036/viewer/2022062305/568149df550346895db70573/html5/thumbnails/23.jpg)
Vancomycin
Mechanism of action Inhibit cell wall synthesis
Antimicrobial spectrum: Narrow spectrum, active only against gram-positi
ve bacteria paticularly staphylococci Pharmacokinetics
Poorly absorbed from intestinal tract, iv Excreted from glomerular filtration 90%
![Page 24: Chapter 38 Macrolides, Lincomycins and Polymycins](https://reader036.vdocuments.pub/reader036/viewer/2022062305/568149df550346895db70573/html5/thumbnails/24.jpg)
Vancomycin
Clinical uses Infection caused by MRSA, MRSE and penicillin-
resistant pneumococcus Treatment of antibiotic-associated enterocolitis ca
used by clostridium difficile po Adverse reaction
Ototoxicity & nephrotoxicity Red-man syndrome
![Page 25: Chapter 38 Macrolides, Lincomycins and Polymycins](https://reader036.vdocuments.pub/reader036/viewer/2022062305/568149df550346895db70573/html5/thumbnails/25.jpg)
Teicoplanin
Similar to vancomycin in mechanism and antimicrobial spectrum
Can be given im as well as iv Less adverse reactions
![Page 26: Chapter 38 Macrolides, Lincomycins and Polymycins](https://reader036.vdocuments.pub/reader036/viewer/2022062305/568149df550346895db70573/html5/thumbnails/26.jpg)
Polymyxins
Active only against gram-negative rods, particularly P.aeruginosa
Mechanism:increase permeability of cell membrane
Mainly used in P.aeruginosa infection when other drugs are resistant
Toxicity: nephrotoxicity & neurotoxicity
![Page 27: Chapter 38 Macrolides, Lincomycins and Polymycins](https://reader036.vdocuments.pub/reader036/viewer/2022062305/568149df550346895db70573/html5/thumbnails/27.jpg)
Baciteracin
Active against gram-positive bacteria Inhibit cell wall formation No cross-resistance with other agents Topical use only because of nephrotoxicity
![Page 28: Chapter 38 Macrolides, Lincomycins and Polymycins](https://reader036.vdocuments.pub/reader036/viewer/2022062305/568149df550346895db70573/html5/thumbnails/28.jpg)