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'鹬 d B c ?泯??????????????? @?????#"  `?? `? 甬? @+& ?d C# 7??  ? @d  ?泯????f?????"???&? Ad   ?泯??????????"??#? Bd   ?泯??????????"??T?? Cd   ?泯??????????"???\痂?  ? ' Dd # ?3穰 Ed  3 ?泯B C<DE连F??????? ??++??vP.1)?6?Glkp?g?d^^??6 *I'PQ^gs??????<"+H<Q6[2c*j"lt??  @              ?"` ? '鹬 Fd  3 ?泯BCPDEF?????? ??? /P@ ?"` ? 鹑2 Gd  c ?泯??????????????? @?????#"  `??@+?B Hd B  ???D??p????"??>` .?B Id  ???D??????"??  痧?  @ Jd  ? ?k? Kd ? ? G???0e???0e??????    B8CDE?F??????? ?? 5%狭?怂 8c8c     ??????1??瘗??? d0u0盱?@T?????y?2 NP'p????'p??A?BCD|E???????H00P?0`XP??Hx??xP(80(?P0@        ?S"??????  ? Ld ? ?;?0e???0e??????    BC`DE?F???ff??? ff? 5%狭?怂 8c8c     ??????1??瘗??? d0u0盱?@T?????y?2 NP'p????'p??A?BCD|E?????%%?8`$D(?pH 8X? P`?p?xpPh?H@ 8?8@H0`?p????8 0@            ?S"??????^ z瘌2 Md ? 3 ??Z? ?????f??8c?????#" `??9  ?? 疠 Nd  ??X]? ???览 ?????"??   ??P '?f3黏2 Od   ?????3烫8c?????#" `??A 疸 Pd  ??xa? ???览 ?????#" `??)  ??A '?f3? Qd  ?????f?????"?? @6? Rd  ???????????"?? K6? Sd  ???????????"??K 6? Td  ???????????"??? 6? Ud  ???????????"?? Q6? Vd  ???????????"??O 6? Wd  ???????????"?? 6疖? ? @?  Xd ?# ? ,? 皎? @+& Yd  ?? @@ ? Zd  ?泯????f?????"???&? [d   ?泯??????????"??#? \d   ?泯??????????"??T?? ]d   ?泯??????????"???\痂?  ? ' ^d # ?3穰 _d  3 ?泯B C<DE连F??????? ??++??vP.1)?6?Glkp?g?d^^??6 *I'PQ^gs??????<"+H<Q6[2c*j"lt??  @              ?"` ? '鹬 `d  3 ?泯BCPDEF?????? ??? /P@ ?"` ? 鹑2 ad  c ?泯??????????????? @?????#"  `??@+鹑2 bd B c ?泯??????????????? @?????#"  `?? `? 鹭? @ h X #  cd  ? ? ? dd B ?泯????f?????"??@ X ! ? ed B  ?泯??????????"??C ? ? fd B  ?泯??????????"??? ! ? gd B  ?泯??????????"?? Q # 痂?  ? ' hd C# ?} h P 穰 id  3 ?泯B C<DE连F??????? ??++??vP.1)?6?Glkp?g?d^^??6 *I'PQ^gs??????<"+H<Q6[2c*j"lt??  @              ?"` ? '鹬 jd  3 ?泯BCPDEF?????? ??? /P@ ?"` ? 稷 kd ? ? ??0e???0e??????    B@CDEF?????? ???????????????????????@ ? ?狭?怂 8c8c     ??????1??瘗??? d0u0盱?@T?????y?2 NP'p????'p??@A?BCD|E???????H?P? @@  ?#" ??  B瘃 ld ???l? ???? ???"?? z   ?? translocase F &?1'? ? md ???? ???? ???"??^ X ??v?0___PPT10??6___PPT9? ??"0??c$ 鹦? @ X ?  nd  ? ?? od B ?泯????f?????"??@ % X ? ? pd B  ?泯??????????"??C $ ? ? ? qd B  ?泯??????????"??? % ? ? rd B  ?泯??????????"?? ' Q ? 痂?  ? ' sd C# ?} P g 穰 td  3 ?泯B C<DE连F??????? ??++??vP.1)?6?Glkp?g?d^^??6 *I'PQ^gs??????<"+H<Q6[2c*j"lt??  @              ?"` ? '鹬 ud  3 ?泯BCPDEF?????? ??? /P@ ?"` ? ?B vd ??D? ???"?? ??  ?t wd A# ???c ; & ?B xd B  ??D?????????  ? ?B yd B  ??D?????????  t疳 zd  ?/?(x? ???? ??????}?>  ??Erythromycin(50S)&?1'?? ?d ???? ???? ???"??]???v?0___PPT10??6___PPT9? ??Inhibit protein synthesis"0?&? ff  ?d  ???? ????? ??????"??v? ???,0Mechanism of action0 &? f3? d ? ????????藿h? ? #d  ???TTr??ff?乔?????????___PPT10?i?G?颁?+D?' ? ????= @B +i?0 鹧? ??   瘀   ?? ?? ???? ??????"??? ???0Clinical uses0&? ??  ??`?? ?? ??????"??<qL????8___PPT10??H___PPT9?*" ?QGram-positive coccus infection staphylococci: bouton (boil) streptococci: pharyngitis, febris rubra streptococcus pneumoniae: pneumonia genuina 2. Corynebacterium diphtheriae 3. Chlamydial infections urethral, endocervical, rectal, epididymal, urogenital 4. Mycoplasmal pneumonia 5. Legionella pneumonia P ?2? &?ff&?f3?&?ff&                  @`???  ? ????????藿h? ? ???TTr??ff?乔??????8?0___PPT10???P???0 ??? ?   瘌   ??,?? ???? ??????"???^  ??? 0Adverse effect0&? f3?   ??? ???? ??????"??~? ??v?0___PPT10??6___PPT9? ??1. Gastrointestinal effects Anorexia, nausea, vomiting, and diarrhea 2. Cholestatic jaundice estolate form of erythromycin 3. Ototoxicity Transient deafness ?&?ff>M  ?   ???? ???? ??????"??9 ????v?0___PPT10??6___PPT9? ??'Contraindications: hepatic dysfunction ((&?ff?  ? ????????藿h? ? ???TTr??ff?乔??????8?0___PPT10???`?/ ?0 }?? 瘐?   瘊   ??P? ???? ??????"???  ???"0Drug resistance0&? f3?  ??艄? ?? ??????"??@Tp ??v?0___PPT10??6___PPT9? ?1. Reduced permeability of the cell membrane or active efflux 2. Modification of the ribosomal binding site 3. Production of esterases that hydrolyze macrolides ?&?ff,?  ?   ??芾? GH??????????#" `??Pj?% ?$D 0 皤?=methylation of an adenine of the 23S bacterial ribosomal RNA .><&??&? 2?  ? ????????藿h? ?  ???TTr??ff?乔??????? ___PPT10??? 席+(z3D?' ? ????= @B D?' ?????= @BA?%?( < +O%?( < +D?' =%(????D?' =%(D袼' =?@B?B?BB0B%(D聒' =1?:Bvisible*?3>?B?style.visibility<? ????????%(D' =+褓4 8??CB#ppt_xBCB#ppt_xB*?3>B ppt_x<? ????????D' =+襻4 8??CB1+#ppt_h/2BCB#ppt_yB*?3>B ppt_y<? ????????+8+0+ 0 +O?0 v? ?   ?  ??惺? ??? ????"??[???v?0___PPT10??6___PPT9? ???"?N0Clarithromycin &?$33?  ??X? ?? ??????"???T$ ??x?0___PPT10??8___PPT9? ??Its activity against Chlamydia, Legionella and Ureaplasma is higher than that of erythromycin. It has lower frequency of gastrointestinal intolerance ???&?ff,  ^ @`???  ? ????????藿h? ? ???33?洙??33???y___PPT10?Y+D?' ? ????= @B +?0   穑?   ?  ??,? ??? ????"??[H??v?0___PPT10??6___PPT9? ??? N0 Azithromycin &?$33 鹫  ??棱? ?? ??????"??/q ??x?0___PPT10??8___PPT9? 鸹?Azithromycin is more active against Haemophilus influenzae and Chlamydia than erythromycin It is less active against streptococci and staphylococci It is now used for urethritis caused by Chlamydia trachomatis. It is rapidly absorbed and well tolerated orally.  ?&?ffZ   n  6 @`???  ? ????????藿h? ? ???TTr??ff?乔?????????___PPT10?i????+D?' ? ????= @B +??0 甬 ??      ??d? ???? ??????< ??Section 2 Lincomycins ? &?(`   ??T? ?? ??????"Z  ??Lincomycin Clindamycin&? f3$  ?  ? ????????藿h? ? ???33?洙??33???y___PPT10?Y+D?' ? ????= @B +?0 )? 鸸?   瘘   ???? ????? ??????"???v????8___PPT10??N___PPT9?0( 鸩??T0 Antibacterial action and Clinical uses 0B+&?$f3&?$f3&?$f3?  ??4? ?? ??????"???,????8___PPT10??N___PPT9?0( ???1. Clindamycin is significantly effective against anaerobic bacteria 2. It is employed primarily in the treatment of infections caused by anaerobic bacteria 3. Enterococci and clostridium difficile are resistant 4. It distributes well into bone, so treats medullitis 5. It does not penetrate into cerebrospinal fluid , not use to treat Epidemic meningitis alone P??&?f3&?ff&?f3"?P   < g?  ? ????????藿h? ? ???TTr??ff?乔?????????___PPT10?i??序S+D?' ? ????= @B +e ?0 痧 ??      ??P? ????? ??????"??  ???$0Adverse effect 0 &?$f3鸱   ??t? ???? ??????"??`? ??v?0___PPT10??6___PPT9? ??9Fatal pseudomembranous colitis Impaired liver function ::&?ff$?  ??? ? G H???????????] `?$D 0 鸨?vancomycin metronidazole P &??&? &??&?$  ?  ? ????????藿h? ?  ???TTr??ff?乔??????? ___PPT10????啼+(z3D?' &? ????= @B D?' ?????= @BA?%?( < +O%?( < +D?' =%(????D?' =%(D袼' =?@B?B?BB0B%(D聒' =1?:Bvisible*?3>?B?style.visibility<? ????????%(D' =+褓4 8??CB#ppt_xBCB#ppt_xB*?3>B ppt_x<? ????????D' =+襻4 8??CB1+#ppt_h/2BCB#ppt_yB*?3>B ppt_y<? ????????+8+0+ 0 +s?0 ?? ??   ?   ???,? ????? ??????"???m+ ??"Section 3 Polypeptide antibiotics D#!&?$`&?$f3&?$`鹉  ???? ?? ??????PZ ????4___PPT10? ?B___PPT9?$ 皙?Vancomycins polymyxins B &?$! &?$f3&?$f3,  ?  ? ????????藿h? ? ???33?洙??33???y___PPT10?Y+D?' ? ????= @B +?0 >? 鹞?   瘊  ??p=? ?? ??????"H ???N0Vancomycin  &?$f3 疖   ???? ???? ??????"??*? ??"    ???? ????? ??????"??? o ???40Antibacterial activity 0 &? f3?  ??8S? ?? ??????"????? ??x?0___PPT10??8___PPT9? ??It is bactericidal agent It is primarily active against gram-positive bacteria (MRSA and MRSE),but enterococci are resistant 3. All species of gram-negative bacilli and mycobacteria are resistant to vancomycin ,Q???&?ff>i ;   @`???  ? ????????藿h? ? ???33?洙??33???y___PPT10?Y+D?' ? ????= @B + ?0 ??  ?   稷    ??A P??? ??????W` 3  P稷    ??A Q??? ??????W?l  Q稷    ??A R??? ??????p? R皎   # ??A??? S??? ??????l  S?? @,   ?M w ?$D 0??  ?t  C# ??P/?B  B  ??D?????????  ? ?B  B  ??D?????????  t    ?????B?style.visibility<? ????????%(D' =+襻4 8??CB0-#ppt_w/2BCB#ppt_xB*?3>B ppt_x<? ????????D' =+褓4 8??CB#ppt_yBCB#ppt_yB*?3>B ppt_y<? ????????+?0 鸺0 ??   痧   ??8f? ????? ??????"?? e????8___PPT10??N___PPT9?0( 穰??H0Clinical use and Adverse effect 0 B%&?$f3&?$f3&?$f3?  ???? ?? ??????"??]????v?0___PPT10??6___PPT9? ?01. Gram-positive bacteria infections: pneumonia, empyema, endocarditis, osteomyelitis, and soft-tissue abscesses, MRSA infection 2. Fatal pseudomembranous colitis due to Clostridium difficile or staphylococci 3. Adverse effects: ototoxicity, nephrotoxicity , "red man syndrome 1?1&?ff?    ? ' ?  ? ????????藿h? ? ???TTr??ff?乔?????????___PPT10?i????O+D?' ? ????= @B +??0 皤@ ??     ??(k? ??? ??????"??P ????N0Polymyxins  &?$f3 瘐  ??T?? ?? ??????"??z ??x?0___PPT10??8___PPT9? 疔?7They are bactericidal agent, active against gram-negative bacilli 2. They increased permeability of the bacterial membrane resulting bacterial cell death 3. They are available for external otitis, corneal ulcers caused by Pseudomonas 4. Adverse effects: nephrotoxicity, neurotoxicity, hypersensitive reaction,C??8&?ff><  @`???  ? ????????藿h? ? ???TTr??ff?乔?????????___PPT10?i??L俱+D?' ? ????= @B +~?0 ?P ??     ???? ??? ??????"?? 9? ??Chapter 38 Aminoglycosides&?(` 疰  ????? ?? ??????"??@? ??v?0___PPT10??6___PPT9? 鹞?>Streptomycin Neomycin Kanamycin Amikacin Gentamicin Tobramycin??&? `P   ?  ? ????????藿h? ? ???33?洙??33???y___PPT10?Y+D?' ? ????= @B +,?0 S?` 疸?     ???? ?? ??????< ???20Antibacterial activity0 0&? ?&? f3?  ???? ?? ??????"???T# ??v?0___PPT10??6___PPT9? ??Antibacterial spectrum :?&?+?  ??l? ?? ??????"??}???v?0___PPT10??6___PPT9? ??All aminoglycosides are bactericidal They are effective against aerobic gram-negative bacilli They are ineffective against anaerobic organisms *? u F?+??&?ff"~ @`???  ? ????????藿h? ? ???33?洙??33???y___PPT10?Y+D?' ? ????= @B +??0 4???p?? ???   ?B  @  ???D??????"?? ? ?B   ?d跟???D??????"???g?9?b   ?Z??G0*H??I??????"??R? ?  @ ?泯????f?????"??? ,?  @  ?泯??????????"??? +?  @  ?泯??????????"?? V ,?  @  ?泯??????????"??O .疣?  ? '  A# ?s 穰   3 ?泯B C<DE连F??????? ??++??vP.1)?6?Glkp?g?d^^??6 *I'PQ^gs??????<"+H<Q6[2c*j"lt??  @              ?"` ? '鹬   3 ?泯BCPDEF?????? ??? /P@ ?"` ? 鹄2  @ c ?泯??????????????? @?????#"  `??k? K )?  ? ? G???0e???0e??????    B8CDE?F??????? ?? 5%狭?怂 8c8c     ??????1??瘗??? d0u0盱?@T?????y?2 NP'p????'p??A?BCD|E???????H00P?0`XP??Hx??xP(80(?P0@        ?S"??????E ?  ? ?;?0e???0e??????    BC`DE?F???ff??? ff? 5%狭?怂 8c8c     ??????1??瘗??? d0u0盱?@T?????y?2 NP'p????'p??A?BCD|E?????%%?8`$D(?pH 8X? P`?p?xpPh?H@ 8?8@H0`?p????8 0@            ?S"??????.X鹦? M5@  # ??S?瘌2  ? 3 ???? ?????f??8c?????#" `??M5- ?? 疠   ??鼗? ???览 ?????"??R ??P '?f3黏2    ?????3烫8c?????#" `??b=@疸   ???? ???览 ?????#" `??s> ??A '?f3甬? ??  # ??{??   ?????f?????"?????   ???????????"??`  ??   ???????????"?? ? ??   ???????????"??o ? ??   ???????????"??? ? ??   ???????????"???  ??   ???????????"??  ?鹪? ? @?   ?# ?? X?=皎? @+&   ?? @@ ?   ?泯????f?????"???&?    ?泯??????????"??#?    ?泯??????????"??T?? !   ?泯??????????"???\痂?  ? ' " # ?3穰 #  3 ?泯B C<DE连F??????? ??++??vP.1)?6?Glkp?g?d^^??6 *I'PQ^gs??????<"+H<Q6[2c*j"lt??  @              ?"` ? '鹬 $  3 ?泯BCPDEF?????? ??? /P@ ?"` ? 鹑2 %  c ?泯??????????????? @?????#"  `??@+鹑2 & B c ?泯??????????????? @?????#"  `?? `? 穰? @+& ' A# 7?? ?).? (  ?泯????f?????"???&? )   ?泯??????????"??#? *   ?泯??????????"??T?? +   ?泯??????????"???\痂?  ? ' , # ?3穰 -  3 ?泯B C<DE连F??????? ??++??vP.1)?6?Glkp?g?d^^??6 *I'PQ^gs??????<"+H<Q6[2c*j"lt??  @              ?"` ? '鹬 .  3 ?泯BCPDEF?????? ??? /P@ ?"` ? 鹑2 /  c ?泯??????????????? @?????#"  `??@+?B 0 @  ???D??p????"?? g?B 1  ???D??????"??;"G? 2 ? ? G???0e???0e??????    B8CDE?F??????? ?? 5%狭?怂 8c8c     ??????1??瘗??? d0u0盱?@T?????y?2 NP'p????'p??A?BCD|E???????H00P?0`XP??Hx??xP(80(?P0@        ?S"??????;} ? 3 ? ?;?0e???0e??????    BC`DE?F???ff??? ff? 5%狭?怂 8c8c     ??????1??瘗??? d0u0盱?@T?????y?2 NP'p????'p??A?BCD|E?????%%?8`$D(?pH 8X? P`?p?xpPh?H@ 8?8@H0`?p????8 0@            ?S"??????( %痧2 4 ? 3 ??劳? ?????f??8c?????#" `??d? ?? 鹫 5 ??刃? ???览 ?????"??q? ??P '?f3?2 6  ?????3烫8c?????#" `??l?疔 7 ??l? ???览 ?????#" `???? ??A '?f3? 8 ?????f?????"??{a? 9 ???????????"???a? : ???????????"??Qa? ; ???????????"??Ga? < ???????????"??a? = ???????????"??Ta? > ???????????"??Oa? ? ?泯????f?????"??E? @  ?泯??????????"??Dq? A  ?泯??????????"??Et? B  ?泯??????????"??G疣?  ? ' C A# ??穰 D  3 ?泯B C<DE连F??????? ??++??vP.1)?6?Glkp?g?d^^??6 *I'PQ^gs??????<"+H<Q6[2c*j"lt??  @              ?"` ? '鹬 E  3 ?泯BCPDEF?????? ??? /P@ ?"` ? 鹄2 F @ c ?泯??????????????? @?????#"  `??j(? G ? ? G???0e???0e??????    B8CDE?F??????? ?? 5%狭?怂 8c8c     ??????1??瘗??? d0u0盱?@T?????y?2 NP'p????'p??A?BCD|E???????H00P?0`XP??Hx??xP(80(?P0@        ?S"?????? j? H ? ?;?0e???0e??????    BC`DE?F???ff??? ff? 5%狭?怂 8c8c     ??????1??瘗??? d0u0盱?@T?????y?2 NP'p????'p??A?BCD|E?????%%?8`$D(?pH 8X? P`?p?xpPh?H@ 8?8@H0`?p????8 0@            ?S"??????{痧2 I ? 3 ??|? ?????f??8c?????#" `??H(? ?? 鹫 J ???? ???览 ?????"??T ??P '?f3?2 K  ?????3烫8c?????#" `??];?疔 L ??H? ???览 ?????#" `??t1 ??A '?f3? M ?????f?????"???? ? N ???????????"???<? ? O ???????????"???? ? P ???????????"???A ? Q ???????????"???A? ? R ???????????"???? ? S ???????????"???I 鹪? ? @?  T ?# ?? 'wa皎? @+& U  ?? @@ ? V  ?泯????f?????"???&? W   ?泯??????????"??#? X   ?泯??????????"??T?? Y   ?泯??????????"???\痂?  ? ' Z # ?3穰 [  3 ?泯B C<DE连F??????? ??++??vP.1)?6?Glkp?g?d^^??6 *I'PQ^gs??????<"+H<Q6[2c*j"lt??  @              ?"` ? '鹬 \  3 ?泯BCPDEF?????? ??? /P@ ?"` ? 鹑2 ]  c ?泯??????????????? @?????#"  `??@+鹑2 ^ B c ?泯??????????????? @?????#"  `?? `? 鹬? @ h X #  _ # ? 7`? ` B ?泯????f?????"??@ X ! ? a B  ?泯??????????"??C ? ? b B  ?泯??????????"??? ! ? c B  ?泯??????????"?? Q # 痂?  ? ' d C# ?} h P 穰 e  3 ?泯B C<DE连F??????? ??++??vP.1)?6?Glkp?g?d^^??6 *I'PQ^gs??????<"+H<Q6[2c*j"lt??  @              ?"` ? '鹬 f  3 ?泯BCPDEF?????? ??? /P@ ?"` ? 鹇 g ? ??0e???0e??????    BCDE?F?????? ???????????????????????@ ?  狭?怂 8c8c     ??????1??瘗??? d0u0盱?@T?????y?2 NP'p????'p??@A?BCD|E?????? ?$H?`Xx????h4 @    ?#" ??X + ? h ????? ?? ??????S / s ??v?0___PPT10??6___PPT9? ??aminoglycosides(30S,A)$?1'???  ?t i A# ]$??p)I?B j B  ??D?????????  ? ?B k B  ??D?????????  t?B l ?  ???D?????????n iQ ?B m  ???D????????? pE ? n ??絮? ?? ???"??P] ?p??v?0___PPT10??6___PPT9? ??%interfere with the initiation complex &0?&?$?+??  ?t o # ?N?0* u ?B p B  ??D?????????  ? ?B q B  ??D?????????  t? r ??? ???? ???"??????v?0___PPT10??6___PPT9? ??)nonfunctional or toxic protein synthesis ,*0?(?$?+? ?? pF s  ?<7? t ? ? G???0e???0e??????    B8CDE?F??????? ?? 5%狭?怂 8c8c     ??????1??瘗??? d0u0盱?@T?????y?2 NP'p????'p??A?BCD|E???????H00P?0`XP??Hx??xP(80(?P0@        ?S"??????r?? u ? ?;?0e???0e??????    BC`DE?F???ff??? ff? 5%狭?怂 8c8c     ??????1??瘗??? d0u0盱?@T?????y?2 NP'p????'p??A?BCD|E?????%%?8`$D(?pH 8X? P`?p?xpPh?H@ 8?8@H0`?p????8 0@            ?S"???????F瘌2 v ? 3 ??4? ?????f??8c?????#" `???}c ?? 疠 w  ?? ? ???览 ?????"???ft ??P '?f3黏2 x   ?????3烫8c?????#" `???k疸 y  ??三? ???览 ?????#" `????t ??A '?f3? z  ?????f?????"??pi? {  ???????????"???i? |  ???????????"??iF? }  ???????????"??<i?? ~  ???????????"???i?   ???????????"??iI? ?  ???????????"??Di?甬? @+& ? C# ??dP'? ?  ?泯????f?????"???&? ?   ?泯??????????"??#? ?   ?泯??????????"??T?? ?   ?泯??????????"???\痂?  ? ' ? # ?3穰 ?  3 ?泯B C<DE连F??????? ??++??vP.1)?6?Glkp?g?d^^??6 *I'PQ^gs??????<"+H<Q6[2c*j"lt??  @              ?"` ? '鹬 ?  3 ?泯BCPDEF?????? ??? /P@ ?"` ? 鹑2 ?  c ?泯??????????????? @?????#"  `??@+甬? @+& ? C# ?tX$? ?  ?泯????f?????"???&? ?   ?泯??????????"??#? ?   ?泯??????????"??T?? ?   ?泯??????????"???\痂?  ? ' ? # ?3穰 ?  3 ?泯B C<DE连F??????? ??++??vP.1)?6?Glkp?g?d^^??6 *I'PQ^gs??????<"+H<Q6[2c*j"lt??  @              ?"` ? '鹬 ?  3 ?泯BCPDEF?????? ??? /P@ ?"` ? 鹑2 ?  c ?泯??????????????? @?????#"  `??@+疣 ?   ?_~+?? ???? ??????,p?D ??Decoding  &??甬 ? ??|? ?? ???"??s =y ??v?0___PPT10??6___PPT9? 稷?2breakup of polysomes into nonfunctional monosomes  30?3?$?+,  ? ?  ???? ???? ??????"??Iw??v?0___PPT10??6___PPT9? ???*0Mechanism of action0 &? ??  ? ????????藿h? ?   ???TTr??ff?乔?????????___PPT10?i?4???+D?' ? ????= @B +?0 6?? 鹌?   鸲  ??H!? ??? ?????"???&??x?0___PPT10??8___PPT9? ??Aminoglycosides must be given parenterally High concentrations accumulate in the renal cortex and in the endolymph and perilymph of the inner ear All may accumulate in fetal plasma and amniotic fluid. All are rapidly excreted into the urine "?&?ffH @  r @`??鹦   ??,1? ????? ??????"??& !????8___PPT10??N___PPT9?0( ???(0Pharmacokinetics 0 B&? f3?& ?+&? f3?  ? ????????藿h? ? f????觋f?f???????y___PPT10?Y+D?' ? ????= @B +7?0 ^??痤?  瘙   ???&? ????? ??????"???? v ??? 0Clinical uses0 &?$f3鸢  ???? ?? ??????"???T ??x?0___PPT10??8___PPT9? ??Aminoglycosides are mostly used to treat infection caused by gram-negative bacteria Penicillin combination with aminoglycoside is used for treatment of enterococcal endocarditis , streptococcal and staphylococcal endocarditis ?&?ffZb  $  @`???  ? ????????藿h? ? ???33?洙??33???y___PPT10?Y+D?' ? ????= @B +a?0 I??鸨?     ??@? ????? ??????"????U  ???"0Adverse effect0 &?$f3鹇  ???? ??? ??????"???j?疴??L___PPT10?,$?~___PPT9?`X ???Ototoxicity ? vestibular dysfunction Injury of cochlear auditory nerve Nephrotoxicity: 3. Neuromuscular paralysis: 4. Allergic reactions: 1ff?91ff?1ff?40ff?&?ff?&?ff&?ff &? ff ?&?ff4 97 ?k#?S3?  ???? ??????????#" `?? ??$D 0 ??Gdizziness, visual extinction, ocular tremor, nausea, vomiting, ataxia. HH&???   ?? o? Gf??H ??????????#" `??% ? ?$D 0 ??4ear noises hearing diminution permanent deafness *53&??"?  ? ????????藿h? ?/  ???33?洙??33? ? ___PPT10?? +' D ' [? ????= @B D袂 ' ?????= @BA?%?( < +O%?( < +D?' =%(????D?' =%(D袼' =?@B?B?BB0B%(D聒' =1?:Bvisible*?3>?B?style.visibility<?????????%(D' =+襻4 8??CB0-#ppt_w/2BCB#ppt_xB*?3>B ppt_x<?????????D' =+褓4 8??CB#ppt_yBCB#ppt_yB*?3>B ppt_y<?????????D?' =%(????D?' =%(D袼' =?@B?B?BB0B%(D聒' =1?:Bvisible*?3>?B?style.visibility<?????????%(D' =+襻4 8??CB0-#ppt_w/2BCB#ppt_xB*?3>B ppt_x<?????????D' =+褓4 8??CB#ppt_yBCB#ppt_yB*?3>B ppt_y<?????????+p+0+0 ++0+0 +??0 鸾??     ??0s? ????? ??????"??? ? ???$0Drug resistance0 &?$f3  ???? ??? ??????"???pj ??x?0___PPT10??8___PPT9? 痼?ySynthesis of enzymes that modify and inactivate aminoglycoside antibiotics. Altered target site Decreased uptake of drug &z1ff?z&?ff0< @`???  ? ????????藿h? ? ???33?洙??33???y___PPT10?Y+D?' ? ????= @B +x?0 ???(??  (疱 ( ???? ?? ????????????8___PPT10??N___PPT9?0( 鸹?-Chapter 39 Tetracyclines and Chloramphenicol >. &?$`?&?$` ?, 鸨 (  ????? ????? ??????"??\??v?0___PPT10??6___PPT9? ??Section 1 Tetracyclines 0&?$`&?$f3 ? (  ???? ???? ??????j甬??<___PPT10??Z___PPT9?<4 ?5Tetracycline Doxycycline Demeclocycline Minocycline V6? &? &? &? f3 &?  f3>  M==--? ( ? ????????藿h? ? ???33?洙??33???y___PPT10?Y+D?' ? ????= @B +J?0 a???,瘃?  ,疒 ,  ??笑? ???? ??????"??W/ ??   ,  ??皓? ????? ??????"???&  ???20Antibacterial activity0 &? f3鹂 , ??杌? ?? ??????"??T?"??x?0___PPT10??8___PPT9? 馥?Tetracyclines are broad spectrum bacteriostatic antibiotics 2. They are active against many gram-positive and gram-negative bacteria 3. They are also active against Rickett's organism, helicoid, mycoplasma and Chlamydia ,1??&?ffZ     @`??? , ? ????????藿h? ? ???TTr??ff?乔?????????___PPT10?i??`7枸+D?' ? ????= @B +?D?0 ??C`KK0?C?  0  0  ???? ????? ??????"??I? ???,0Mechanism of action0 &? f3? 0 ??h? ??? ??????"?????x?0___PPT10??8___PPT9? ??tetracyclines enter microorganism by passive diffusion and an energy-dependent process of active transport. tetracyclines bind reversibly to the 30S subunit of the bacterial ribosome "&?ff$ a ? @`????? Pa6 0 ?P 6?=? P36 0 ?Pa6疒 0  ??? ???? ??????&0?? ???  疒 0  ???? ???? ??????VP ???  鹄?  ?? 0# ?u?P?$D 0?  0? ? G???0e???0e??????    B8CDE?F??????? ?? 5%狭?怂 8c8c     ??????1??瘗??? d0u0盱?@T?????y?2 NP'p????'p??A?BCD|E???????H00P?0`XP??Hx??xP(80(?P0@        ?S"??????"o?  0 ? ?;?0e???0e??????    BC`DE?F???ff??? ff? 5%狭?怂 8c8c     ??????1??瘗??? d0u0盱?@T?????y?2 NP'p????'p??A?BCD|E?????%%?8`$D(?pH 8X? P`?p?xpPh?H@ 8?8@H0`?p????8 0@            ?S"???????瘌2  0? 3 ???? ?????f??8c?????#" `??M#- ?? 疠  0 ??暂? ???览 ?????"??W ??P '?f3黏2  0  ?????3烫8c?????#" `??b+@疸 0 ??d? ???览 ?????#" `??w9 ??A '?f3? 0 ?????f?????"?? ? ? 0 ???????????"??A? ? 0 ???????????"??? ? 0 ???????????"??F ? 0 ???????????"??F ? 0 ???????????"??? ? 0 ???????????"??N ? 0 ?泯????f?????"?? 8p? 0  ?泯??????????"??5o? 0  ?泯??????????"??}p? 0  ?泯??????????"??'?r痂?  ? ' 0C# ?(F穰 0 3 ?泯B C<DE连F??????? ??++??vP.1)?6?Glkp?g?d^^??6 *I'PQ^gs??????<"+H<Q6[2c*j"lt??  @              ?"` ? '鹬 0 3 ?泯BCPDEF?????? ??? /P@ ?"` ? 鹑2 0B c ?泯??????????????? @?????#"  `??nw,穰? Cy 0# ? ?0? 0? ? G???0e???0e??????    B8CDE?F??????? ?? 5%狭?怂 8c8c     ??????1??瘗??? d0u0盱?@T?????y?2 NP'p????'p??A?BCD|E???????H00P?0`XP??Hx??xP(80(?P0@        ?S"?????? _?  0 ? ?;?0e???0e??????    BC`DE?F???ff??? ff? 5%狭?怂 8c8c     ??????1??瘗??? d0u0盱?@T?????y?2 NP'p????'p??A?BCD|E?????%%?8`$D(?pH 8X? P`?p?xpPh?H@ 8?8@H0`?p????8 0@            ?S"??????w瘌2 !0? 3 ??荜? ?????f??8c?????#" `??9?6 ?? 疠 "0 ???? ???览 ?????"???k ??P '?f3黏2 #0  ?????3烫8c?????#" `??>u;疸 $0 ??祚? ???览 ?????#" `??tk ??A '?f3? %0 ?????f?????"??C?y? &0 ???????????"???/? '0 ???????????"??/?u? (0 ???????????"??m?? )0 ???????????"???? *0 ???????????"???>? +0 ???????????"??:??甬? @+& ,0C# ?I k? -0 ?泯????f?????"???&? .0  ?泯??????????"??#? /0  ?泯??????????"??T?? 00  ?泯??????????"???\痂?  ? ' 10# ?3穰 20 3 ?泯B C<DE连F??????? ??++??vP.1)?6?Glkp?g?d^^??6 *I'PQ^gs??????<"+H<Q6[2c*j"lt??  @              ?"` ? '鹬 30 3 ?泯BCPDEF?????? ??? /P@ ?"` ? 鹑2 40 c ?泯??????????????? @?????#"  `??@+甬? @+& 50C# ?A!c? 60 ?泯????f?????"???&? 70  ?泯??????????"??#? 80  ?泯??????????"??T?? 90  ?泯??????????"???\痂?  ? ' :0# ?3穰 ;0 3 ?泯B C<DE连F??????? ??++??vP.1)?6?Glkp?g?d^^??6 *I'PQ^gs??????<"+H<Q6[2c*j"lt??  @              ?"` ? '鹬 <0 3 ?泯BCPDEF?????? ??? /P@ ?"` ? 鹑2 =0 c ?泯??????????????? @?????#"  `??@+疴? @+& >0C# ?? ?$D 0? ?0 ?泯????f?????"???&? @0  ?泯??????????"??#? A0  ?泯??????????"??T?? B0  ?泯??????????"???\痂?  ? ' C0# ?3穰 D0 3 ?泯B C<DE连F??????? ??++??vP.1)?6?Glkp?g?d^^??6 *I'PQ^gs??????<"+H<Q6[2c*j"lt??  @              ?"` ? '鹬 E0 3 ?泯BCPDEF?????? ??? /P@ ?"` ? 鹑2 F0 c ?泯??????????????? @?????#"  `??@+  G0  ?=??? ?? ??????"??036 ??Tetracyclines (30S,A)$?1'?  鹭B H0?  ?d跟???D??????"??4 ;?$D 0鹄?  ?t I0C# ???b?$D??? 0?B J0B  ??D?????????  ? ?B K0B  ??D?????????  t? 0 ? ????????藿h? ? ???33?洙??33???y___PPT10?Y+D?' ? ????= @B +'?0 >? 4鹞?  4? 4  ??? ???? ??????"??<? ??v?0___PPT10??6___PPT9? ???&0Pharmacokinetics0 &?$f3  4 ?? ? ?? ??????"??"????8___PPT10??H___PPT9?*" 鹭? Tetracyclines are adequately but incompletely absorbed after oral ingestion 2. Tetracyclines cross the placental barrier and concentrate in fetal bones and dentition 3. Tetracyclines are metabolized in liver and then are excreted from kidney, except doxycycline J/?}?a?&?ff?&?ffH H M D  @`??? 4 ? ????????藿h? ? ???TTr??ff?乔?????????___PPT10?i???0+D?' ? ????= @B +?0 鹂?8??  8瘙 8  ??? ????? ??????"?? v ??? 0Clinical uses0 &?$f3 8 ???? ?? ??????"??]&,??x?0___PPT10??8___PPT9? ??Rickettsial infection: fever, chill, ache in bones and joints Chlamydiae infection: pneumonia , urethritis, trachelitis, ophthalmia and trachoma Mycoplasma infection: mycoplasmal pneumonia Spirochetal infection: lyme disease Bacterial infection: cholera  ?&?ff 3        ) @`??? 8 ? ????????藿h? ? ???TTr??ff?乔?????????___PPT10?i??+D?' ? ????= @B +$?0 ;??<鹚?  <疒 <  ???? ???? ??????"?? ??  痿 < ??x;? ??? ??????"??? v ???"0Adverse effect 0&?$f3鸬 < ??T=? ?? ??????"??[ ??x?0___PPT10??8___PPT9? ??Gastric discomfort: Nausea, vomiting, and diarrhea Bony structures and Teeth :discoloration and hypoplasia of the teeth and a temporary stunting of growth Fatal hepatotoxicity: in pregnant women Phototoxicity: severe sunburn >?&?ff"!&?ff>b 7  @`??? < ? ????????藿h? ? ???TTr??ff?乔?????????___PPT10?i??0J+D?' ? ????= @B +?0  ?@黏?  @? @ ???? ?? ??????"????m??v?0___PPT10??6___PPT9? ??p4. Vestibular problems: dizziness, nausea, vomiting 5. Pseudotumor cerebri: Benign intracranial hypertension , headache , blurred vision 6. Superinfections: pseudomembranous enterocolitis caused by Clostridium difficile. 7. Contraindications: renally-impaired patients , pregnant or breast-feeding women, or in children \under 8 years of age. q?q&?ff?8 K  l @`??? @ ? ????????藿h? ? ???TTr??ff?乔?????????___PPT10?i???iOv+D?' ? ????= @B +?0 瘥?D??  D D  ??lM? ????? ??????"??X w ???$0Drug resistance0 0&?$f3&? ?? D ??Hh? ?? ??????"??] ??x?0___PPT10??8___PPT9? ??Decreased intracellular accumulation production of protected proteins that interfere with tetracycline binding to the ribosome Enzymatic inactivation of tetracyclines  ?&?ff$?  @`??? D ? ????????藿h? ? ???TTr??ff?乔?????????___PPT10?i??@2+D?' ? ????= @B +T?0 {??H ?  H H  ???? ????? ??????"??.t ??Section 2 Chloramphenicol&?$`  H  ??hz? ????? ??????"????  ???00 Antibacterial action0 &? f3? H ???? ?? ??????"??P??? ??x?0___PPT10??8___PPT9? ??Chloramphenicol is either bacteriostatic or bactericidal It is active against both aerobic and anaerobic gram-positive and gram-negative organisms It has effective against rickettsiae, helicoids, Chlamydia and mycoplasma.  ?&?ffH ?   @`??? H ? ????????藿h? ? ???33?洙??33???y___PPT10?Y+D?' ? ????= @B +??0 ?疰A??KKL?A?  L??  y@  L ? ? L? ? G???0e???0e??????    B8CDE?F??????? ?? 5%狭?怂 8c8c     ??????1??瘗??? d0u0盱?@T?????y?2 NP'p????'p??A?BCD|E???????H00P?0`XP??Hx??xP(80(?P0@        ?S"?????? X{ ? L ? ?;?0e???0e??????    BC`DE?F???ff??? ff? 5%狭?怂 8c8c     ??????1??瘗??? d0u0盱?@T?????y?2 NP'p????'p??A?BCD|E?????%%?8`$D(?pH 8X? P`?p?xpPh?H@ 8?8@H0`?p????8 0@            ?S"???????? @ 瘌2 L? 3 ???? ?????f??8c?????#" `??6]  ?? 疠 L ???? ???览 ?????"??J? f  ??P '?f3黏2 L  ?????3烫8c?????#" `??K)e 疸 L ???? ???览 ?????#" `??j? f  ??A '?f3?  L ?????f?????"?? c y ?  L ???????????"??*c ? ?  L ???????????"???c  ?  L ???????????"??c / ?  L ???????????"??/c ? ? L ???????????"???c  ? L ???????????"??c 7 甬? @+& LC# ?9^! ? L ?泯????f?????"???&? L  ?泯??????????"??#? L  ?泯??????????"??T?? L  ?泯??????????"???\痂?  ? ' L# ?3穰 L 3 ?泯B C<DE连F??????? ??++??vP.1)?6?Glkp?g?d^^??6 *I'PQ^gs??????<"+H<Q6[2c*j"lt??  @              ?"` ? '鹬 L 3 ?泯BCPDEF?????? ??? /P@ ?"` ? 鹑2 L c ?泯??????????????? @?????#"  `??@+甬? @+& LC# ? R ? L ?泯????f?????"???&? L  ?泯??????????"??#? L  ?泯??????????"??T?? L  ?泯??????????"???\痂?  ? ' L# ?3穰 L 3 ?泯B C<DE连F??????? ??++??vP.1)?6?Glkp?g?d^^??6 *I'PQ^gs??????<"+H<Q6[2c*j"lt??  @              ?"` ? '鹬  L 3 ?泯BCPDEF?????? ??? /P@ ?"` ? 鹑2 !L c ?泯??????????????? @?????#"  `??@+??  @ "L ?0x ?$D 0? #L? ? G???0e???0e??????    B8CDE?F??????? ?? 5%狭?怂 8c8c     ??????1??瘗??? d0u0盱?@T?????y?2 NP'p????'p??A?BCD|E???????H00P?0`XP??Hx??xP(80(?P0@        ?S"??????  ? $L ? ?;?0e???0e??????    BC`DE?F???ff??? ff? 5%狭?怂 8c8c     ??????1??瘗??? d0u0盱?@T?????y?2 NP'p????'p??A?BCD|E?????%%?8`$D(?pH 8X? P`?p?xpPh?H@ 8?8@H0`?p????8 0@            ?S"??????^ z瘌2 %L? 3 ???? ?????f??8c?????#" `??9  ?? 疠 &L ??摩? ???览 ?????"??  ??P '?f3黏2 'L  ?????3烫8c?????#" `??A 疸 (L ??洫? ???览 ?????#" `??5  ??A '?f3? )L ?????f?????"?? @6? *L ???????????"?? K6? +L ???????????"??K 6? ,L ???????????"??? 6? -L ???????????"?? Q6? .L ???????????"??O 6? /L ???????????"?? 6疖? ? @?  0L?# ? ,? 皎? @+& 1L ?? @@ ? 2L ?泯????f?????"???&? 3L  ?泯??????????"??#? 4L  ?泯??????????"??T?? 5L  ?泯??????????"???\痂?  ? ' 6L# ?3穰 7L 3 ?泯B C<DE连F??????? ??++??vP.1)?6?Glkp?g?d^^??6 *I'PQ^gs??????<"+H<Q6[2c*j"lt??  @              ?"` ? '鹬 8L 3 ?泯BCPDEF?????? ??? /P@ ?"` ? 鹑2 9L c ?泯??????????????? @?????#"  `??@+鹑2 :LB c ?泯??????????????? @?????#"  `?? `? 鹭? @ h X #  ;L ? ? ? LB  ?泯??????????"??? ! ? ?LB  ?泯??????????"?? Q # 痂?  ? ' @LC# ?} h P 穰 AL 3 ?泯B C<DE连F??????? ??++??vP.1)?6?Glkp?g?d^^??6 *I'PQ^gs??????<"+H<Q6[2c*j"lt??  @              ?"` ? '鹬 BL 3 ?泯BCPDEF?????? ??? /P@ ?"` ? 鹭 CL  ??p? ???? ??????"??w ??  ? DL # ?M?x? ??????????? ?  ?$D 0 ??Peptidyl transferaseF$??$ 鹭 EL  ??嗑? ???? ??????"??}, ? ??  痱 FL  ??? ???? ??????"??m? ??Chloramphenicol(50S,A)&?`  GL  ??渑? ????? ??????"??  ???,0Mechanism of action0 &?$f3鹦B HL?  ?d跟???D??????"??v ?$D 0??  ?t ILA# < ?P ?B JLB  ??D?????????  ? ?B KLB  ??D?????????  t? L ? ????????藿h? ? ???TTr??ff?乔?????????___PPT10?i??滥?+D?' ? ????= @B +?0 ?瘅?P??  P鹞 P  ??(? ????? ??????"?? ? ????8___PPT10??N___PPT9?0( ???&0pharmacokinetics0 B&?$f3&?$f3&?$f3? P ??溆? ?? ???????&f? ??x?0___PPT10??8___PPT9? ??Chloramphenicol may be administered either intravenously or orally It penetrate blood-brain barrier, placental barrier, blood-ocular barrier It is inactivated by conjugation with glucuronic acid in liver, secreted by the renal tubule.?&?ff"$ - @`??? P ? ????????藿h? ? ???33?洙??33???y___PPT10?Y+D?' ? ????= @B +6?0 ]?T痦?  T痱 T ???? ??? ??????"??< $  ??? 0Clinical uses0 &?$f3鸹 T ??? ?? ??????"????l??x?0___PPT10??8___PPT9? 稹? Bacterial meningitis: meningococcal meningitis Rickettsial infections: typhus or Rocky Mountain spotted fever Eye infection: outer eye infection, intraocular infection, eyeball infection Anaerobic infection: peritoneal abscess, pelvic inflammation and peritonitis @?.&?ff"&?ff0  @`??? T ? ????????藿h? ? ???33?洙??33???y___PPT10?Y+D?' ? ????= @B +?0 痤@dX??  X鹦 X ??? ??? ??????"??? ?????8___PPT10??N___PPT9?0( ???"0Adverse effect0 T&?$?&?$?&?$?&?$f3? X ?? ? ??? ??????"??? I1 ????8___PPT10??H___PPT9?*" ???Bone marrow depression Aplastic anemia Gray baby syndrome: poor feeding, depressed breathing, cardiovascular collapse, cyanosis \=?R?;&?ff""?L&?ffp @`??? X ? ????????藿h? ? ???TTr??ff?乔?????????___PPT10?i??例;?+D?' ? ????= @B +E?0 \??\痨?  \痄 \  ???????? ??????"??& ?????8___PPT10??N___PPT9?0( ???&0Drug resistance 0 X'?$f3&?$f3&?$f3'?$f3鹑 \ ??H}??? ??????"???m ??x?0___PPT10??8___PPT9? 皎??Produce inactivator? acetyl coenzyme A transferase Membrane permeability is decreased, chloramphenicol penetrate the organism less"???&?ffH  % @`??? \ ? ????????藿h? ? ???TTr??ff?乔?????????___PPT10?i?????+D?' ????= @B +阜,x?旒w\?梢/>?甫us暂醺?戟k0? A连?? 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