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TTrff0 ~v (     0,m  D9    P*    0m   9   \* d  c $ ?F     08u   <   8USQdkYkHre,g7h_ ,{N~ ,{ N~ ,{V~ ,{N~    6|  >Dw    Z*   6"  > w   \* H  0phΗ ? ̙3380___PPT10.j0 $(  $ $ 0d  D9    R*"   $ 0   9   ^*"  $ 6,  >Dw    \*"  $ 6\  > w   ^*" H $ 0phΗ ? ̙3380___PPT10.`) 0 P)`(  ` ` N? ??"<tT ( Lactam Antibiotics&(`$   ` Zx? ??"  t40 Antibacterial activity 0$0& ` ` HH ?"]| e Penicillins$ 0 &(`  `  `HGH-̙??#" ` FI,$D0 KGram-positive coccus Gram-negative coccus Gram-positive bacilli Helicoids ,LK&ff"6"H ` 0޽h ?` fff___PPT10v.`C-7+(ED'  = @B D' = @BA?%,( < +O%,( < +D' =%(D' =%(DT' =A@BBB B0B%(D' =1:Bvisible*o3>+B#style.visibility<*`%(D' =-6B'blinds(horizontal)*<3<*`+8+0+`0 +d 0 { s d (  d` d T ?"=   ~v0___PPT106___PPT9 H"0c$  d T ?"> H"0c$  d TP ?"&s H"0c$  d TDf ?"OV H"0c$  d Nf? ??"&H lSemisynthetic penicillin&$`   d  `q ??"7D~v0___PPT106___PPT9 /Penicillinase-resistant penicillin( Oxacillin )@0$& ` $3& `$   d Tf ??@& ~v0___PPT106___PPT9 8 (1) They kill penicillinase-producing staphylococci (2) They can t kill Methicillin-resistant strains of Staphylococcus aureus (MRSA) &ffF 1 3 @`H d 0޽h ? TTrff___PPT10i.܉ h+D=' = @B +0 `,h(  h h Zf? ??"Y_~v0___PPT106___PPT9 *Extended spectrum penicillins (Ampicillin)L+& ` $& ` ,   h Z!f ??"f |0___PPT10<___PPT9  _They are more effective against gram-negative bacilli They can not kill pseudomonas aeruginosa ``&ffU  @` h  `1fG@H̙??#" `6  ~v0___PPT106___PPT9 6Antipseudomonal penicillins Carbenicillin Piperacillin,7&3H   H h 0޽h ?h TTrff___PPT10i.݉+D=' f= @B +*0 ))0q33l/)(  l{ l ND?f? ??"<m~v0___PPT106___PPT9 iCephalosporins Feature& `  l TTCf ?"*  L&0gf3  l TTGf ?"` J$0'f3  l H4Jf ?"  b &0gf3#~ &S l# #"*PPPP&S l N|Tf f3?"V   R Df3 @` l N Xf f3?"` V  R Df3 @`  l Ngf f3?"| `   P Df3 @`  l Njf f3?"& |   Y anaerobes  %f3 @`  l N|yf f3?"V`   R Df3 @`  l N$rf f3?"` ` V  P Df3 @`  l Nf f3?"| ` `  P Df3 @` l Nf f3?"&` |  Pseudomonas aeruginosa%f3  @` l NLf f3?"V S P Df3 @` l Nf f3?"`  VS R Df3 @` l NHf f3?"|  ` S n Df3 @`  l Nf f3?"& | S u nephrotoxic  %f3  @` l Nf f3?"V`  p Df3 @` l Nf f3?"` V`  n Df3 @` l Nf f3?"| ` `  R Df3 @`0 l N +f f3?"&| `  G D%f3-f3%f3 @` l Nf f3?"V R Df3 @` l Nf f3?"` V n Df3 @` l Nf f3?"| `  p Df3 @`0 l Ng f3?"&|  G D%f3-f3%f3 @`~ l Ng f3?"VVNF___PPT9(   Third: " d%f3f3 @` l NLg f3?"` V q Second%f3 @` l N&g f3?"| `  q First%f3 @`D l N/g f3?"&| F>6___PPT9 b& " df3  @`B l B1?"&| B  l B1?"&S| SB !l B1?"&&B "l B1?"B #l B1?"&&B $l B1?"B %l B1?"&& B &l B1?" B 'l B1?"& & B (l B1?"  B )l B1?"& &SB *l B1?" SB +l B1?"| ` B ,l B1?"` VB -l B1?"VB .l B1?"| S` SB /l B1?"` SVSB 0l B1?"VSSB 1l NDf3|?"&B 2l NDf3|?"&B 3l NDf3|?"0&0H l 0޽h ? TTrff___PPT10i.݉<+D=' f= @B + 0 5 -  p(  p p T̲g ?"z* H"0c$ / p T$g ?"W Y Imipenem + cilastatin@0&!" &!$  p Tg ?"z H"0c$  p Tg ?"q  H"0c$  p Hg ?" B  qClavulanic acid + Amoxicillin&!   p Ng? ??"T 8Other -lactams antibiotics &(`  p T8g ??@| _ Carbapenems  & `   p Zg ??" ;H ~v0___PPT106___PPT9 ,-lactamase inhibitors& `  H p 0޽h ? TTrff___PPT10i.މٍ+D=' = @B +0 0 (   B  Zg? ??"mi  FMacrolides Lincomycins Polypeptide antibiotics GG&$`$  &  T8g ?"J  v Chapter 37 N &(`&,`&(`"$H  0޽h ? 3333y___PPT10Y+D=' g= @B +0 OG@(  v  Tg ??" ~v0___PPT106___PPT9 ^ Macrolides  &$` )  T@g ??";  )Erythromycin Clarithromycin Azithromycin **& f3,  H  0޽h ? TTrff80___PPT10.PP0 P Y(     N ? ??",<8___PPT10N___PPT90( N0Erythromycin B&$33 &$33&$33v  T  ??"a ~v0___PPT106___PPT9 ^$0Pharmacokinetics0& f3  T  ??"T`8___PPT10H___PPT9*" Erythromycin base is destroyed by gastric acid It distributes well to all body fluids including prostatic fluid ,but it does not enter the cerebrospinal fluid (CSF) Erythromycin is extensively metabolized and is excreted in the bile, and only 5% is excreted in the urine. :&ff"`  @`H  0޽h ? 3333y___PPT10Y+D='  = @B +0 H@` (      `  ??"  <     fTg? ??"&. 1 n40Antibacterial activity 0 & f3  T%  ??"D x0___PPT108___PPT9 Erythromycin is bacteriostatic It is effective against gram-positive organisms It is active against some gram-negative organisms Mycoplasma, Chlamydozoan, Legionella and campylobacteria are susceptible.  &ffbf    @`H  0޽h ? TTrff80___PPT10.Ղ;l0 kkpzd Ak(  d ~F C   d  6\ d  G0e0e    B8CDEdF,  5% 8c8c     ?1 d0u0@Ty2 NP'p<'pA)BCD|EH00P0`XPHxxP(80(P0@        S"E  d  F;0e0e    BC`DEF<ff ff 5% 8c8c     ?1 d0u0@Ty2 NP'p<'pA)BCD|E%%8`$D(pH 8X P`pxpPhH@ 88@H0`p8 0@            S"  2 d 3 r0 f8c?#" `pIP :  d  Z3  ?"|9 =P 'f32  d   `38c?#" `Qc  d  Zl7  ?#" `Y =A 'f3  d  Tf?"CF  d  Z?"dF  d  Z?"F d  Z?"iF d  Z?"iF d  Z?"F d  Z?"qF d B Zf?"s) d B  `?"v( d B  `?"). d B  `?"'+T  ' d C# k d  3 hB C<DEFDb ++vP.1)6Glkpgd^^6 *I'PQ^gs<"+H<Q6[2c*j"lt  @              "` ' d  3 BCPDEFb  /P@ "` 2 d B c  @?#"  `w#F G d  z{ d B Zf?"G_ d B  `?"J d B  `?" d B  `?"XT  ' d C# W_  d  3 hB C<DEFDb ++vP.1)6Glkpgd^^6 *I'PQ^gs<"+H<Q6[2c*j"lt  @              "` ' !d  3 BCPDEFb  /P@ "` 2 "d B c  @?#"  `Kb #d @  `G'HI?"BW 4F  < $d  5 H\ %d  G0e0e    B8CDEdF,  5% 8c8c     ?1 d0u0@Ty2 NP'p<'pA)BCD|EH00P0`XPHxxP(80(P0@        S" MW &d  F;0e0e    BC`DEF<ff ff 5% 8c8c     ?1 d0u0@Ty2 NP'p<'pA)BCD|E%%8`$D(pH 8X P`pxpPhH@ 88@H0`p8 0@            S"ngY<T M5@ 'd #  c2 (d 3 rpD f8c?#" `M5- :  )d  ZxG  ?"R =P 'f32 *d   `38c?#" `b=@ +d  ZK  ?#" `s> =A 'f3T  ,d # 7 -d  Tf?" .d  Z?"`   /d  Z?"   0d  Z?"o   1d  Z?"   2d  Z?"   3d  Z?"  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Q6 Vd  Z?"O 6 Wd  Z?" 6T  @  Xd #  , N @+& Yd   @@  Zd  Zf?"& [d   `?"# \d   `?"T ]d   `?"\T  ' ^d # 3 _d  3 hB C<DEFDb ++vP.1)6Glkpgd^^6 *I'PQ^gs<"+H<Q6[2c*j"lt  @              "` ' `d  3 BCPDEFb  /P@ "` 2 ad  c  @?#"  `@+2 bd B c  @?#"  ` ` N @ h X #  cd     dd B Zf?"@ X !  ed B  `?"C  fd B  `?" !  gd B  `?" Q # T  ' hd C# } h P  id  3 hB C<DEFDb ++vP.1)6Glkpgd^^6 *I'PQ^gs<"+H<Q6[2c*j"lt  @              "` ' jd  3 BCPDEFb  /P@ "`  kd  f0e0e    B@CDEF @  Ԕ 8c8c     ?1 d0u0@Ty2 NP'p<'p@A)BCD|E?HP @@  #"   B ld Tl  ?" z   _ translocase F &1' ` md Tq  ?"^ X ~v0___PPT106___PPT9 H"0c$ F @ X  nd    od B Zf?"@ % X  pd B  `?"C $  qd B  `?" %  rd B  `?" ' Q T  ' sd C# } P g  td  3 hB C<DEFDb ++vP.1)6Glkpgd^^6 *I'PQ^gs<"+H<Q6[2c*j"lt  @              "` ' ud  3 BCPDEFb  /P@ "` B vd TD ?" L  t wd A# tc ; & B xd B  `DԔ??   B yd B  `DԔ??  t zd  f/(x  ??}>  KErythromycin(50S)&1'o d T|  ?"]~v0___PPT106___PPT9 WInhibit protein synthesis"0& ff  d  f ? ??"v f,0Mechanism of action0 & f3H d 0޽h ? #d  TTrff___PPT10i.G`+D='  = @B +i0  i(      `  ??"? X0Clinical uses0& 33  T`  ??"<qL8___PPT10H___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&                  @`H  0޽h ? TTrff80___PPT10.قP>0 } (      `,  ??"^  Z 0Adverse effect0& f3P   `  ??"~ ~v0___PPT106___PPT9 ,1. Gastrointestinal effects Anorexia, nausea, vomiting, and diarrhea 2. Cholestatic jaundice estolate form of erythromycin 3. Ototoxicity Transient deafness &ff>M     `  ??"9 ~v0___PPT106___PPT9 a'Contraindications: hepatic dysfunction ((&ffH  0޽h ? TTrff80___PPT10.`/ 0 }u (      `P  ??"  \"0Drug resistance0& f30  T  ??"@Tp ~v0___PPT106___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,     ` GHm??#" `Pj% ,$D 0 =methylation of an adenine of the 23S bacterial ribosomal RNA .><&3&3 2H  0޽h ?  TTrff ___PPT10. ϯ+(z3D'  = @B DD' = @BA?%,( < +O%,( < +D{' =%(D#' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<* %(D' =+4 8?\CB#ppt_xBCB#ppt_xB*Y3>B ppt_x<* D' =+4 8?dCB1+#ppt_h/2BCB#ppt_yB*Y3>B ppt_y<* +8+0+ 0 +O0 vn (     Nʔ ? ??"[~v0___PPT106___PPT9 ~"N0Clarithromycin &$336  TXڔ  ??"T$ x0___PPT108___PPT9 Its activity against Chlamydia, Legionella and Ureaplasma is higher than that of erythromycin. It has lower frequency of gastrointestinal intolerance &ff,  ^ @`H  0޽h ? 3333y___PPT10Y+D='  = @B +0   (     N,ޔ ? ??"[H~v0___PPT106___PPT9 | N0 Azithromycin &$33   T  ??"/q x0___PPT108___PPT9 Azithromycin is more active against Haemophilus influenzae and Chlamydia than erythromycin It is less active against streptococci and staphylococci It is now used for urethritis caused by Chlamydia trachomatis. It is rapidly absorbed and well tolerated orally.  &ffZ   n  6 @`H  0޽h ? TTrff___PPT10i.(+D='  = @B +0  F(      `d  ??< uSection 2 Lincomycins  &(`   TT  ??"Z  }Lincomycin Clindamycin& f3$  H  0޽h ? 3333y___PPT10Y+D='  = @B +0 )! (      f ? ??"v8___PPT10N___PPT90( T0 Antibacterial action and Clinical uses 0B+&$f3&$f3&$f3}  T4  ??",8___PPT10N___PPT90( E1. 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   < gH  0޽h ? TTrff___PPT10i.S+D='  = @B +e 0  p(      fP ? ??"  ^$0Adverse effect 0 &$f3   `t  ??"` ~v0___PPT106___PPT9 9Fatal pseudomembranous colitis Impaired liver function ::&ff$o  Z G HZ??] `,$D 0 vancomycin metronidazole P &3&3 &3&3$  H  0޽h ?  TTrff ___PPT10.+(z3D' & = @B DD' = @BA?%,( < +O%,( < +D{' =%(D#' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<* %(D' =+4 8?\CB#ppt_xBCB#ppt_xB*Y3>B ppt_x<* D' =+4 8?dCB1+#ppt_h/2BCB#ppt_yB*Y3>B ppt_y<* +8+0+ 0 +s0  *(   &   f, ? ??"m+ "Section 3 Polypeptide antibiotics D#!&$`&$f3&$`  T.  ??PZ 4___PPT10 B___PPT9$ Vancomycins polymyxins B &$! &$f3&$f3,  H  0޽h ? 3333y___PPT10Y+D='  = @B +0 >6 (     Tp=  ??"H vN0Vancomycin  &$f3    `?  ??"* >"    fB ? ??" o n40Antibacterial activity 0 & f3  T8S  ??" x0___PPT108___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 ;   @`H  0޽h ? 3333y___PPT10Y+D='  = @B + 0   (       fA P? ??W` 3  P    fA Q? ??Wl  Q    fA R? ??p R   # lA S? ??l  S&z @,   M w ,$D 0T  t  C# P/B  B  `DԔ??   B  B  `DԔ??  t    fY+B#style.visibility<* %(D' =+4 8?dCB0-#ppt_w/2BCB#ppt_xB*Y3>B ppt_x<* D' =+4 8?\CB#ppt_yBCB#ppt_yB*Y3>B ppt_y<* +0 0 T(      f8f ? ??" e8___PPT10N___PPT90( H0Clinical use and Adverse effect 0 B%&$f3&$f3&$f3$  Tf  ??"]~v0___PPT106___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 11&ff    ? ' H  0޽h ? TTrff___PPT10i.5O+D='  = @B +0 @ C(     Z(k ? ??"P vN0Polymyxins  &$f3   TT  ??"z x0___PPT108___PPT9 7They are bactericidal agent, active against gram-negative bacilli 2. They increased permeability of the bacterial membrane resulting bacterial cell death 3. They are available for external otitis, corneal ulcers caused by Pseudomonas 4. Adverse effects: nephrotoxicity, neurotoxicity, hypersensitive reaction,C8&ff><  @`H  0޽h ? TTrff___PPT10i.L+D='  = @B +~0 P 5(     Z ? ??" 9 wChapter 38 Aminoglycosides&(`   T  ??"@ ~v0___PPT106___PPT9 >Streptomycin Neomycin Kanamycin Amikacin Gentamicin Tobramycin??& `P   H  0޽h ? 3333y___PPT10Y+D='  = @B +,0 SK` (     T؜  ??< ~20Antibacterial activity0 0& 3& f3j  T  ??"T# ~v0___PPT106___PPT9 RAntibacterial spectrum :&+/  Tl  ??"}~v0___PPT106___PPT9 All aminoglycosides are bactericidal They are effective against aerobic gram-negative bacilli They are ineffective against anaerobic organisms * u F+&ff"~ @`H  0޽h ? 3333y___PPT10Y+D='  = @B +0 4,p (   B  @  `D)?"  B   fdD)?"g9b   fZG0*H)I?"R   @ Zf?" ,  @  `?" +  @  `?" V ,  @  `?"O .L  '  A# s    3 hB C<DEFDb ++vP.1)6Glkpgd^^6 *I'PQ^gs<"+H<Q6[2c*j"lt  @              "` '   3 BCPDEFb  /P@ "` 2  @ c  @?#"  `k K )T   G0e0e    B8CDEdF,  5% 8c8c     ?1 d0u0@Ty2 NP'p<'pA)BCD|EH00P0`XPHxxP(80(P0@        S"E    F;0e0e    BC`DEF<ff ff 5% 8c8c     ?1 d0u0@Ty2 NP'p<'pA)BCD|E%%8`$D(pH 8X P`pxpPhH@ 88@H0`p8 0@            S".XL M5@  # S2  3 r f8c?#" `M5- :    Zػ  ?"R =P 'f32    `38c?#" `b=@   Z  ?#" `s> =A 'f3L   # {   Tf?"   Z?"`     Z?"     Z?"o     Z?"     Z?"     Z?"  L  @   #  X=N @+&    @@    Zf?"&    `?"#    `?"T !   `?"\T  ' " # 3 #  3 hB C<DEFDb ++vP.1)6Glkpgd^^6 *I'PQ^gs<"+H<Q6[2c*j"lt  @              "` ' $  3 BCPDEFb  /P@ "` 2 %  c  @?#"  `@+2 & B c  @?#"  ` ` L @+& ' A# 7 ). (  Zf?"& )   `?"# *   `?"T +   `?"\T  ' , # 3 -  3 hB C<DEFDb ++vP.1)6Glkpgd^^6 *I'PQ^gs<"+H<Q6[2c*j"lt  @              "` ' .  3 BCPDEFb  /P@ "` 2 /  c  @?#"  `@+B 0 @  `Dp?" gB 1  `D)?";"GT 2  G0e0e    B8CDEdF,  5% 8c8c     ?1 d0u0@Ty2 NP'p<'pA)BCD|EH00P0`XPHxxP(80(P0@        S";}  3  F;0e0e    BC`DEF<ff ff 5% 8c8c     ?1 d0u0@Ty2 NP'p<'pA)BCD|E%%8`$D(pH 8X P`pxpPhH@ 88@H0`p8 0@            S"( %2 4 3 r͖ f8c?#" `d :  5 ZЖ  ?"q =P 'f32 6  `38c?#" `l 7 ZlՖ  ?#" ` =A 'f3 8 Tf?"{a 9 Z?"a : Z?"Qa ; Z?"Ga < Z?"a = Z?"Ta > Z?"Oa ? Zf?"E @  `?"Dq A  `?"Et B  `?"GL  ' C A#  D  3 hB C<DEFDb ++vP.1)6Glkpgd^^6 *I'PQ^gs<"+H<Q6[2c*j"lt  @              "` ' E  3 BCPDEFb  /P@ "` 2 F @ c  @?#"  `j(T G  G0e0e    B8CDEdF,  5% 8c8c     ?1 d0u0@Ty2 NP'p<'pA)BCD|EH00P0`XPHxxP(80(P0@        S" j H  F;0e0e    BC`DEF<ff ff 5% 8c8c     ?1 d0u0@Ty2 NP'p<'pA)BCD|E%%8`$D(pH 8X P`pxpPhH@ 88@H0`p8 0@            S"{2 I 3 r| f8c?#" `H( :  J Z  ?"T =P 'f32 K  `38c?#" `]; L ZH  ?#" `t1 =A 'f3 M Tf?"  N Z?"<  O Z?"  P Z?"A  Q Z?"A  R Z?"  S Z?"I L  @  T #  'waN @+& U   @@  V  Zf?"& W   `?"# X   `?"T Y   `?"\T  ' Z # 3 [  3 hB C<DEFDb ++vP.1)6Glkpgd^^6 *I'PQ^gs<"+H<Q6[2c*j"lt  @              "` ' \  3 BCPDEFb  /P@ "` 2 ]  c  @?#"  `@+2 ^ B c  @?#"  ` ` L @ h X #  _ #  7` ` B Zf?"@ X !  a B  `?"C  b B  `?" !  c B  `?" Q # T  ' d C# } h P  e  3 hB C<DEFDb ++vP.1)6Glkpgd^^6 *I'PQ^gs<"+H<Q6[2c*j"lt  @              "` ' f  3 BCPDEFb  /P@ "`  g  0e0e    BCDE4F @    8c8c     ?1 d0u0@Ty2 NP'p<'p@A)BCD|E? $H`Xxh4 @    #" X + ^ h Z.  ??S / s ~v0___PPT106___PPT9 Naminoglycosides(30S,A)$1'L  t i A# ]$p)IB j B  `DԔ??   B k B  `DԔ??  tB l  fDԔ??n iQ B m  fCDԔ?? pE m n H  ?"P] p~v0___PPT106___PPT9 a%interfere with the initiation complex &0&$+L  t o # kN0* u B p B  `DԔ??   B q B  `DԔ??  t r T  ?"~v0___PPT106___PPT9 q)nonfunctional or toxic protein synthesis ,*0($+ F pF s  <7\ t  G0e0e    B8CDEdF,  5% 8c8c     ?1 d0u0@Ty2 NP'p<'pA)BCD|EH00P0`XPHxxP(80(P0@        S"r u  F;0e0e    BC`DEF<ff ff 5% 8c8c     ?1 d0u0@Ty2 NP'p<'pA)BCD|E%%8`$D(pH 8X P`pxpPhH@ 88@H0`p8 0@            S"F2 v 3 r4 f8c?#" `}c :  w  Z  ?"ft =P 'f32 x   `38c?#" `k y  Z  ?#" `t =A 'f3 z  Tf?"pi {  Z?"i |  Z?"iF }  Z?"<i ~  Z?"i   Z?"iI   Z?"DiT @+&  C# dP'   Zf?"&    `?"#    `?"T    `?"\T  '  # 3   3 hB C<DEFDb ++vP.1)6Glkpgd^^6 *I'PQ^gs<"+H<Q6[2c*j"lt  @              "` '   3 BCPDEFb  /P@ "` 2   c  @?#"  `@+T @+&  C# tX$   Zf?"&    `?"#    `?"T    `?"\T  '  # 3   3 hB C<DEFDb ++vP.1)6Glkpgd^^6 *I'PQ^gs<"+H<Q6[2c*j"lt  @              "` '   3 BCPDEFb  /P@ "` 2   c  @?#"  `@+    f_~+  ??,pD BDecoding  &  H|  ?"s =y ~v0___PPT106___PPT9 2breakup of polysomes into nonfunctional monosomes  303$+,     f  ??"Iw~v0___PPT106___PPT9 f*0Mechanism of action0 & 3H  0޽h ?   TTrff___PPT10i.4K\+D='  = @B +0 6. (     ZH! ? ?"&x0___PPT108___PPT9 Aminoglycosides must be given parenterally High concentrations accumulate in the renal cortex and in the endolymph and perilymph of the inner ear All may accumulate in fetal plasma and amniotic fluid. All are rapidly excreted into the urine "&ffH @  r @`   f,1 ? ??"& !8___PPT10N___PPT90( (0Pharmacokinetics 0 B& f3& +& f3H  0޽h ? fffy___PPT10Y+D='  = @B +70 ^V(     f& ? ??" v Z 0Clinical uses0 &$f3  T:  ??"T x0___PPT108___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  $  @`H  0޽h ? 3333y___PPT10Y+D='  = @B +a0 IA(     f@ ? ??"U  \"0Adverse effect0 &$f3  ZN ? ??"jL___PPT10,$~___PPT9`X @Ototoxicity  vestibular dysfunction Injury of cochlear auditory nerve Nephrotoxicity: 3. Neuromuscular paralysis: 4. Allergic reactions: 1ff91ff1ff40ff&ff9&ff&ff & ff &ff4 97 k#S3M  Ti ̙??#" ` ,$D 0 Gdizziness, visual extinction, ocular tremor, nausea, vomiting, ataxia. HH&3R   ` o GfH ̙??#" `%  ,$D 0 z4ear noises hearing diminution permanent deafness *53&3"H  0޽h ?/  3333  ___PPT10 +' D ' [ = @B D ' = @BA?%,( < +O%,( < +D{' =%(D#' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*%(D' =+4 8?dCB0-#ppt_w/2BCB#ppt_xB*Y3>B ppt_x<*D' =+4 8?\CB#ppt_yBCB#ppt_yB*Y3>B ppt_y<*D{' =%(D#' =%(D' =A@BBBB0B%(D' =1:Bvisible*o3>+B#style.visibility<*%(D' =+4 8?dCB0-#ppt_w/2BCB#ppt_xB*Y3>B ppt_x<*D' =+4 8?\CB#ppt_yBCB#ppt_yB*Y3>B ppt_y<*+p+0+0 ++0+0 +0 U(     f0s ? ??"  ^$0Drug resistance0 &$f3  Zw ? ??"pj x0___PPT108___PPT9 ySynthesis of enzymes that modify and inactivate aminoglycoside antibiotics. Altered target site Decreased uptake of drug &z1ffz&ff0< @`H  0޽h ? 3333y___PPT10Y+D='  = @B +x0 (/(  ( ( T셜  ??8___PPT10N___PPT90( -Chapter 39 Tetracyclines and Chloramphenicol >. &$`!&$` ,  (  f ? ??"\~v0___PPT106___PPT9 Section 1 Tetracyclines 0&$`&$f3 Q (  `  ??j<___PPT10Z___PPT9<4 5Tetracycline Doxycycline Demeclocycline Minocycline V6 & & & f3 &  f3>  M==--H ( 0޽h ? 3333y___PPT10Y+D='  = @B +J0 aY,(  , ,  `Ц  ??"W/ <   ,  f ? ??"&  l20Antibacterial activity0 & f3 , T軜  ??"T"x0___PPT108___PPT9 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     @`H , 0޽h ? TTrff___PPT10i.`7+D='  = @B +D0 CC`KK08C(  0  0  f ? ??"I? f,0Mechanism of action0 & f3Y 0 ZhĜ ? ??"x0___PPT108___PPT9 9tetracyclines 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 ? @`?F Pa6 0 P 6o=N P36 0 Pa6 0  `Ҝ  ??&0 B   0  `М  ??VP B     0# u?P,$D 0\  0  G0e0e    B8CDEdF,  5% 8c8c     ?1 d0u0@Ty2 NP'p<'pA)BCD|EH00P0`XPHxxP(80(P0@        S""o  0  F;0e0e    BC`DEF<ff ff 5% 8c8c     ?1 d0u0@Ty2 NP'p<'pA)BCD|E%%8`$D(pH 8X P`pxpPhH@ 88@H0`p8 0@            S"2  0 3 rڜ f8c?#" `M#- :   0 Zݜ  ?"W =P 'f32  0  `38c?#" `b+@ 0 Zd  ?#" `w9 =A 'f3 0 Tf?"   0 Z?"A  0 Z?"  0 Z?"F  0 Z?"F  0 Z?"  0 Z?"N  0 Zf?" 8p 0  `?"5o 0  `?"}p 0  `?"'rT  ' 0C# (F 0 3 hB C<DEFDb ++vP.1)6Glkpgd^^6 *I'PQ^gs<"+H<Q6[2c*j"lt  @              "` ' 0 3 BCPDEFb  /P@ "` 2 0B c  @?#"  `nw,T Cy 0#  0\ 0  G0e0e    B8CDEdF,  5% 8c8c     ?1 d0u0@Ty2 NP'p<'pA)BCD|EH00P0`XPHxxP(80(P0@        S" _  0  F;0e0e    BC`DEF<ff ff 5% 8c8c     ?1 d0u0@Ty2 NP'p<'pA)BCD|E%%8`$D(pH 8X P`pxpPhH@ 88@H0`p8 0@            S"w2 !0 3 r f8c?#" `96 :  "0 Z  ?"k =P 'f32 #0  `38c?#" `>u; $0 Z  ?#" `tk =A 'f3 %0 Tf?"Cy &0 Z?"/ '0 Z?"/u (0 Z?"m )0 Z?" *0 Z?"> +0 Z?":T @+& ,0C# I k -0 Zf?"& .0  `?"# /0  `?"T 00  `?"\T  ' 10# 3 20 3 hB C<DEFDb ++vP.1)6Glkpgd^^6 *I'PQ^gs<"+H<Q6[2c*j"lt  @              "` ' 30 3 BCPDEFb  /P@ "` 2 40 c  @?#"  `@+T @+& 50C# A!c 60 Zf?"& 70  `?"# 80  `?"T 90  `?"\T  ' :0# 3 ;0 3 hB C<DEFDb ++vP.1)6Glkpgd^^6 *I'PQ^gs<"+H<Q6[2c*j"lt  @              "` ' <0 3 BCPDEFb  /P@ "` 2 =0 c  @?#"  `@+ @+& >0C#  ,$D 0 ?0 Zf?"& @0  `?"# A0  `?"T B0  `?"\T  ' C0# 3 D0 3 hB C<DEFDb ++vP.1)6Glkpgd^^6 *I'PQ^gs<"+H<Q6[2c*j"lt  @              "` ' E0 3 BCPDEFb  /P@ "` 2 F0 c  @?#"  `@+  G0  `=  ??"036 gTetracyclines (30S,A)$1'  B H0  fdD)?"4 ;,$D 0  t I0C# Sb,$D 0B J0B  `DԔ??   B K0B  `DԔ??  tH 0 0޽h ? 3333y___PPT10Y+D='  = @B +'0 >6 4(  4 4  `  ??"< ~v0___PPT106___PPT9 `&0Pharmacokinetics0 &$f3  4 T  ??""8___PPT10H___PPT9*"  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&ffa&ffH H M D  @`H 4 0޽h ? TTrff___PPT10i.k0+D='  = @B +0 8W(  8 8  f ? ??" v Z 0Clinical uses0 &$f3 8 T"  ??"]&,x0___PPT108___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        ) @`H 8 0޽h ? TTrff___PPT10i.+D='  = @B +$0 ;3<(  < <  `,  ??" <   < Zx; ? ??" v \"0Adverse effect 0&$f3 < TT=  ??"[ x0___PPT108___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  @`H < 0޽h ? TTrff___PPT10i.0J+D='  = @B +0  @(  @l @ ZO  ??"m~v0___PPT106___PPT9 Np4. 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. qq&ff8 K  l @`H @ 0޽h ? TTrff___PPT10i.iOv+D='  = @B +0 D(  D D  flM ? ??"X w p$0Drug resistance0 0&$f3& 3? D THh  ??"] x0___PPT108___PPT9 %Decreased intracellular accumulation production of protected proteins that interfere with tetracycline binding to the ribosome Enzymatic inactivation of tetracyclines  &ff$  @`H D 0޽h ? TTrff___PPT10i.@2+D='  = @B +T0 {sH (  H H  fu ? ??".t uSection 2 Chloramphenicol&$`  H  fhz ? ??"  j00 Antibacterial action0 & f3 H T~  ??"P x0___PPT108___PPT9 Chloramphenicol is either bacteriostatic or bactericidal It is active against both aerobic and anaerobic gram-positive and gram-negative organisms It has effective against rickettsiae, helicoids, Chlamydia and mycoplasma.  &ffH    @`H H 0޽h ? 3333y___PPT10Y+D='  = @B +B0 AAKKL~A(  LF  y@  L  \ L  G0e0e    B8CDEdF,  5% 8c8c     ?1 d0u0@Ty2 NP'p<'pA)BCD|EH00P0`XPHxxP(80(P0@        S" X{  L  F;0e0e    BC`DEF<ff ff 5% 8c8c     ?1 d0u0@Ty2 NP'p<'pA)BCD|E%%8`$D(pH 8X P`pxpPhH@ 88@H0`p8 0@            S" @ 2 L 3 rԐ f8c?#" `6]  :  L Zؓ  ?"J f  =P 'f32 L  `38c?#" `K)e  L Z  ?#" `j f  =A 'f3  L Tf?" c y   L Z?"*c    L Z?"c    L Z?"c /   L Z?"/c   L Z?"c   L Z?"c 7 T @+& LC# 9^!  L Zf?"& L  `?"# L  `?"T L  `?"\T  ' L# 3 L 3 hB C<DEFDb ++vP.1)6Glkpgd^^6 *I'PQ^gs<"+H<Q6[2c*j"lt  @              "` ' L 3 BCPDEFb  /P@ "` 2 L c  @?#"  `@+T @+& LC#  R  L Zf?"& L  `?"# L  `?"T L  `?"\T  ' L# 3 L 3 hB C<DEFDb ++vP.1)6Glkpgd^^6 *I'PQ^gs<"+H<Q6[2c*j"lt  @              "` '  L 3 BCPDEFb  /P@ "` 2 !L c  @?#"  `@+$z  @ "L 0x ,$D 0\ #L  G0e0e    B8CDEdF,  5% 8c8c     ?1 d0u0@Ty2 NP'p<'pA)BCD|EH00P0`XPHxxP(80(P0@        S"   $L  F;0e0e    BC`DEF<ff ff 5% 8c8c     ?1 d0u0@Ty2 NP'p<'pA)BCD|E%%8`$D(pH 8X P`pxpPhH@ 88@H0`p8 0@            S"^ z2 %L 3 r f8c?#" `9  :  &L ZĦ  ?"  =P 'f32 'L  `38c?#" `A  (L Z䪞  ?#" `5  =A 'f3 )L Tf?" @6 *L Z?" K6 +L Z?"K 6 ,L Z?" 6 -L Z?" Q6 .L Z?"O 6 /L Z?" 6T  @  0L#  , N @+& 1L  @@  2L Zf?"& 3L  `?"# 4L  `?"T 5L  `?"\T  ' 6L# 3 7L 3 hB C<DEFDb ++vP.1)6Glkpgd^^6 *I'PQ^gs<"+H<Q6[2c*j"lt  @              "` ' 8L 3 BCPDEFb  /P@ "` 2 9L c  @?#"  `@+2 :LB c  @?#"  ` ` N @ h X #  ;L    LB  `?" !  ?LB  `?" Q # T  ' @LC# } h P  AL 3 hB C<DEFDb ++vP.1)6Glkpgd^^6 *I'PQ^gs<"+H<Q6[2c*j"lt  @              "` ' BL 3 BCPDEFb  /P@ "`  CL  `p  ??"w :  J DL # lMx ??   ,$D 0 zPeptidyl transferaseF$$  EL  `ྞ  ??"},  :   FL  fž  ??"m NChloramphenicol(50S,A)&`  GL  fŞ ? ??"  f,0Mechanism of action0 &$f3B HL  fdD)?"v ,$D 0L  t ILA# < P B JLB  `DԔ??   B KLB  `DԔ??  tH L 0޽h ? TTrff___PPT10i.iJ+D='  = @B +0 P(  P P  f(̞ ? ??"  8___PPT10N___PPT90( &0pharmacokinetics0 B&$f3&$f3&$f3 P TӞ  ??&f x0___PPT108___PPT9 uChloramphenicol may be administered either intravenously or orally It penetrate blood-brain barrier, placental barrier, blood-ocular barrier It is inactivated by conjugation with glucuronic acid in liver, secreted by the renal tubule.&ff"$ - @`H P 0޽h ? 3333y___PPT10Y+D='  = @B +60 ]UT(  T T Z ? ??"< $  Z 0Clinical uses0 &$f3 T T  ??"lx0___PPT108___PPT9  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  @`H T 0޽h ? 3333y___PPT10Y+D='  = @B +0 @dX(  X X Z ? ??" 8___PPT10N___PPT90( "0Adverse effect0 T&$3&$3&$3&$f3v X Z ? ??" 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