《药理学》课程PPT教学课件（Antimicrobial Drugs）42 Tetracyclines, Chloramphenicol

Tetracyclines 四环素andChloramphenicol氯霉素

Tetracyclines 四环素 and Chloramphenicol 氯霉素

1.TETRACYCLINESThe first tetracycline was obtained in 1948 from a StreptomycesbacteriumTetracyclines are broad-spectrum antimicrobial drugsThey enter into cells by a mechanism not present in the cells ofmammals2

2 1. TETRACYCLINES The first tetracycline was obtained in 1948 from a Streptomyces bacterium Tetracyclines are broad-spectrum antimicrobial drugs They enter into cells by a mechanism not present in the cells of mammals

Mechanism of Action of TetracvclinesaminoAAribosomeacidAAAAtransferantiRNAAAcodon(tRNA)anticodoncodoncodonPAmessengerRNA(mRNA)Tetracyclines四环素类bindreversiblytothe3ossubunit,andcompetewithtRNAfortheAsite.Theyarethereforebacteriostatic细菌抑制的drugs3

3 Mechanism of Action of Tetracyclines Tetracyclines 四环素类 bind reversibly to the 30S subunit, and compete with tRNA for the A site. They are therefore bacteriostatic 细菌抑制的 drugs

Entry into BacteriaTetracyclines enter intogram(-) bacteria by passivediffusionthroughtheporinsGram +ofthe outermembrane,thickcellwallandbyactivetransport主动扩散throughtheinnermembrane of both gram(+)Gram-and gram(-) bacteriathin cell wallcomplexoutermembraneATP国ADPporinsOur cells do not have that transport mechanism

4 Entry into Bacteria Tetracyclines enter into gram(-) bacteria by passive diffusion through the porins of the outer membrane, and by active transport 主动 扩散 through the inner membrane of both gram(+) and gram(-) bacteria Our cells do not have that transport mechanism

Molecular Structures of TetracyclinesCHaCH3OHN(CH3)2HCH.OHOHHOHCONH,OHICONH20OHOHOOH00OHOHdoxycyclineTetracyclineTetracyclines arebig,fluorescent,lipophilic,moleculesDoxycycline强力霉素andminocycline二甲胺四环素aremorelipophilicthantetracycline5

5 Molecular Structures of Tetracyclines Tetracyclines are big, fluorescent, lipophilic, molecules Doxycycline 强力霉素 and minocycline 二甲胺四环素 are more lipophilic than tetracycline

Common Tetracycline DrugsMinocycline二甲胺四环素anddoxycycline强力霉素arethemost commonly used orally because they are more lipophilicandbetterabsorbedChlortetracycline氯四环素andoxytetracycline氧四环素areusedineyeointments6

6 Common Tetracycline Drugs Minocycline 二甲胺四环素 and doxycycline 强力霉素 are the most commonly used orally because they are more lipophilic and better absorbed Chlortetracycline 氯四环素 and oxytetracycline 氧四环素 are used in eye ointments

ttrum of IetracyclinesRicketsiaChlamydia-pneumoniaeotherCorynebacterium-trachomatisacnes-psittacigram+bacillichlamydi衣原体Mycoplasmamycofirst-plasmapneumoniaeline痤疮gramusesspiroentericchetesotherrodsgram-Borrelia burgdorferibacilli(Lyme diseaseTreponemapallidumVibrio choleraTularemiameningitis(syphilis)Yersiniapestis Brucella霍乱，瘟疫，野兔病，布鲁氏菌莱姆病霍乱7

7 Spectrum of Tetracyclines first￾line uses 霍乱, 瘟疫, 野兔病, 布鲁氏菌 莱姆病 衣原体 痤疮 霍乱

Administration of TetracyclinesFood reduces the absorption of tetracycline, but not ofdoxycyclinenorminocyclineCa++,Mg++,A/+++andFe+++ionsformchelates螯合物withtetracyclines,impairing their absorption.Antacidmedicines and dairy products should be avoidedDoxycyclineand minocycline are also administered IV8

8 Administration of Tetracyclines Food reduces the absorption of tetracycline, but not of doxycycline nor minocycline Ca++, Mg++, Al+++ and Fe+++ ions form chelates 螯合物 with tetracyclines, impairing their absorption. Antacid medicines and dairy products should be avoided Doxycycline and minocycline are also administered IV

Distribution of Tetracyclinespassage into thecentralnervoussystemaccumulationinteethand boneTetracyclines behave as lipophilic drugsaccumulation inliverand fattissuespassagethroughthe placenta(and intothemilk)passage intotheprostate

9 Distribution of Tetracyclines Tetracyclines behave as lipophilic drugs

Elimination of Tetracyclinesminocyclineisextensivelymetabolized inthe liverthe main route of excretion isthekidney,withthe exception ofdoxycyclinetetracyclines are excreted inthebile,and reabsorbed inthe intestinethey have a long-lasting action10

10 Elimination of Tetracyclines they have a long-lasting action