farmakologi antibiotik
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FARMAKOLOGIANTIBIOTIK
NASRUHAN ARIFIANTOSTIFAR – SUNAN GIRIPONOROGO
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nciples of antibacterial terap!
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How Can We InhibitBacteria?
Bacteristatic
◦ Inhibits a vital pathway used in the growthof the bacteria, but does not directly
cause deathBactericidal
◦ Disrupts bacterial function so much that
death will occur
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What anner Can We !ill?
"ime#dependent
◦ Drug concentration must remainconstantly above the minimum inhibitory
concentration $IC% lactams, vancomycin
Concentration#dependent
◦ Drug concentration must reach a certainconcentration, many times based on thearea under the curve $'(C% )luoro*uinolones
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What Can We Disrupt?
Cell Wall
)olic 'cid ynthesis
-ucleic 'cid ynthesis.ibosome
Cell embrane
/
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Cell Wall Inhibitors
0
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ibitors of "ell #all S!ntesis
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)ig1 212 implied scheme of bacterial cell wall synthesis showing siteof action of cell wall#active antibiotics1 $.eproduced from edicalicrobiology, 2/th 4dition by David 5reenwood $6773%, withpermission from 4lsevier
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Cell Wall 'gents
actams
◦ 9enicillins
◦ Cephalosporins
◦ onbactams
◦ Carbapenems
5lycopeptides
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actam ubtypes
'll share a lactam ring, therebyhaving the same mechansim of action$and e:plaining the cross#sensitivity
between classes%◦ 9enicillins
◦ Cephalosporins
◦ onobactams◦ Carbapenems
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9enicillin Classications
-arrow#spectrum penicillins9enicillinase#resistant penicillins
4:tended#spectrum penicillins
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-arrow#pectrum9enicillins
9enicillin 5 $9f;ierpen◦ ore active against Neiserra and
anaerobes
9enicillin = $9en#=ee !
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9enicillinase#.esistant'gents
Clo:acillin $Clo:apen
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4:tended#spectrum 9C-s
'minopenicillinsCarbo:ypenicillins
(reidopenicillins
2+
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'minopenicillins
'gents
◦ 'mpicillin $>mnipen
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Carbo:ypenicillins
'gents
◦ Carbenicillin $5eopen
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actamase Inhibitors
Chemicals with no antibacterialactivity that irreversiblyinactivate lactamase
◦ ulbactam With ampicillin $(nasyn
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Cephalosporins
pectra of activity $generation%
'naerobic activity $Cephamycins%
'nti#pseudomonal activityethyltetra;olethiomethyl side#chain
etabolismGelimination
Cerebrospinal uid penetrance
2J
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2st 5eneration 'gents
Cefa;olin $'ncef
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2st 5enerationCephalosporins
5reat 5ram @A activity
-o activity against enterococci orListeria monocytogenes
ainstay of choice for uncomplicatedcommunity ac*uired infections
94c! activity◦ Proteus
◦ E. coli
◦ Klebsiella
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6nd 5eneration 'gents
Cefaclor $Ceclor
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6nd 5enerationCephalosporins
ore 5ram @# activity than 2st generation agents
>ften used for ("Is and (.Is
H4-94c! activity◦ H. infuenzae◦ Enterobacter K $rapid resistance occurs%
◦ Neisseria◦ Proteus◦ E. coli
◦ Klebsiella
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3rd 5eneration 'gents
Cefdinir $>mnicef
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3rd 5enerationCephalosporinsHave even better 5ram @#
coverage than second generationagents
8oses more 5ram @A coverage4:tra coverage against Serratia
and Moraxella catarrhalis
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th 5enerationCephalosporinsCefepime $a:ipime
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"he 5eneration9rogression's one moves up in
cephalosporin generation, more5ram @# activity is seen
Conse*uently, 5ram @A activityis decreased advancing ingeneration
th generation has 5ram @#activity without sacricing 5ram@A activity
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'nti#9seudomonalCephalosporins
3rd 5eneration◦ Cefopera;one
◦ Cefta;idime
th 5eneration◦ Cefepime
"he 3rd generation anti#
pseduomonal agents lose evenmore 5ram @A activity thanother 3rd generation agents
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Cephalosporin 4limination
)or the most part, all are renal withfew e:ceptions
"he L;onesM are hepatic
◦ Cefopera;one
◦ Ceftria:one
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C) penetrance
6nd 5eneration◦ Cefuro:ime 5enerally not used due to decreased eNcacy
3rd 5eneration◦ Cefota:ime O/#P dosing 'gent of choice in neonatal meningitis $along
with ampicillin%◦ Ceftria:one O26#6P dosing 'gent of choice for adult meningitis Causes Qernicterus in neonates
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onobactams
';treonam $';actam
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Carbapenems
ore resistant to hydrolysis fromlactamases
=ery broad spectrum with
coverage of 5ram @A $not.'%, 5ram @#, anaerobes, andPseudomonas aeruginosa
Higher incidence of sei;ure thanother lactam agents
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Carbapenem 'gents
'gents
◦ 4rtapenem $Invan;
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5lycopeptides
=ancomycin $=ancocin
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=ancomycin pectrum
5ram @A aerobes
.'
9enicillin#resistant pneumococcus
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)olic 'cid ynthesis
Inhibitors
3
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)olic 'cid Inhibitors
LulfasM
◦ Inhibit dihydropteroate synthetase, anen;yme involved in the synthesis of
bacterial folic acid "rimethoprim
◦ Inhibit dihydrofolate reductase, an
en;yme necessary for thymidine synthesisBoth are bacteriostatic
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)olic 'cid Inhibitor 4
.ashes◦ tevens#Rohnson syndrome
'ngioedema
Hemolytic anemia-ephroto:icity
◦ =ia precipitation of crystals of the inactivemetabolite
Crosses the placenta◦ !ernicturus
◦ hould be avoided in pregnancy and in childrenunder 6 months of age
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-ucleic 'cid
ynthesis Inhibitors
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)luoro*uinolones
Inhibit D-' topoisomerase II $D-'gyrase%
Bacteriostatic
Divided into generationsS reverse ofthe reverse of cepholosporins $actualclassication varies between sources%◦
Cephalosporins progress from 5ram @Ato 5ram @# activity, but loses 5ram @A
◦ )luoro*uinolones progress from 5ram @#to 5ram @A activity, but retains 5ram
@# 3
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2st 5eneration )Os
-alidi:ic 'cid $-eg5ram
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6nd 5eneration )Os
'gents
◦ Cino:acin $Cinobac
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'dvanced 6nd 5eneration)Os
'gents
◦ Ciproo:acin $Ciproo:acin $)lo:in
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3rd 5eneration )O 'gents
'gents◦ 5atio:acin $"e*uin
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th 5eneration )O 'gents
'gents
◦ 'latroo:acin $"rovan
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)O ide 4Tects
Comple:es with cations
9hotosensitivity
CU9+7 interactions
.enal elimination
O" prolongation!orsades de Pointes
Hepatic failure $"rovan<
% "endon rupture
◦ Do not give if V2yo
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.ibosomal Inhibitors
+2
Inibitors of Protein S!ntesis
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Inibitors of Protein S!ntesis
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Inhibitors
"etracyclines
◦ Bind to amino acyl t#.-' portion of them.-'#ribosome comple:
◦ Bacteriostatic'minoglycosides
◦ Bind to the separated 37s subunit causing
misreading◦ Bacteriocidal
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"etracyclines
Demeclocycline $Declomycin
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"etracycline pectrum
5ram @A Bacilli
5ram @# .ods
5ram @# Bacilli
◦ H1 inuen;ae, =ibrio cholerapirochetes
◦ Borrelia burgdorferi $8yme d;%, treponemapallidum $syphilis%
Chlamydia
.icQettsia ricQettsii $.ocQy t1 potted)ever%
+0
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"etracycline 4
Chelates with cations◦ Decreased absorption with dairy, calcium
◦ Deposition on calcied tissues
5I upset9hototo:icityDemeclocycline
◦
-ever used as an antibiotic because it caninduce nephrogenic diabetes insipidus
◦ (sed in treatment of I'DH
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'minoglycocides
'miQacin $'miQin
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'minoglycocide pectrum
5ram @# Bacteria
◦ 9seudomonas aeruginosa
◦ =ibrio cholerae
◦ Uersinia pestis $98'5(4%
◦ 4nterobacter aerogenes
◦ 41 coli
◦ !lebsiella pneumoneae◦ 9roteus
◦ erratia
/2
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'minoglycocide 4
Highly polar $cationic% molecules,usually prevents 5I absorption
.enally eliminated
◦ >toto:icity
◦ -ephroto:icity
-eomycin#used topically, orally for
hepatic failuretreptomycin#used in "B
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acrolides
';alides◦ ';ithromycin $Fithroma:
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acrolide pectrum
Chlamydia $4rythro drug ofchoice in pregnancy%
ycoplasma pneumoniae
◦ (reaplasma urealyticum8egionella pneumophila
"reponema pallidum $yphillis%
5ram $A% cocci5ram $A% bacilli
/+
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acrolide pectrum
ClarithroEerythro◦ Chlamydia, 8egionella, (reaplasma
H1 u
';ithroVerythro◦ taph, trep
';ithroEerythro
◦
H1 u, mora:ella catarrhalis $whyused for pneumonia%
//
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acrolide 4
4rythro destroyed by gastric acid◦ 4nteric coated or esteried forms
';ithro concentrates in
neutrophils, macrophages,broblasts4rythro ';ithroXhepaticS
clarithroXrenal4
◦ -=D, cholestatic Yaundice $estolatesalt#erythro%, 4rythro Z clarithro gothrough CU9+7
/0
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8incomycins
Clindamycin $Cleocin
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8incomycin pectrum
5ram @A aerobes5ram @A anaerobes5ram @# anaerobes
-> gram @# aerobic coverage "hinQ of these as 6nd#line
penicillins
02
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8incomycin 4
.ash-eutropenia "hrombocytopenia
4rythema multiforme $rare%9seudomembranous colitis
06
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Chloramphenicol
Broad spectrum against 5ram@A, 5ram @#, and anaerobes1
Can be e:tremely to:ic◦
Dose#related revesible anemia◦ Hemolytic anemia in 5/9D
deciency
◦ Dose#independent aplastic anemia
◦ L5rey baby syndromeM caused bydrug accumulation leading tocyanosis, cardiovascular collapseand eventual death
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Cell embrane
Inhibitors
0
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Cell embrane Inhibitors
Daptomycin $Cubicin
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9('" I-)>.'I >B'" $9I>%
9C1 I!'"'- '9>"4!4. I-D>-4I' $I'I%9>->.>5>
-'.(H'- '.I)I'-">, 1)arm1, 1)arm1!lin1,'pt1W' 723323330BB 633D/074
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elamat belaYar[1