FARMAKOLOGI ANTIBIOTIK

8/17/2019 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

6+


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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

3+


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)olic 'cid ynthesis

Inhibitors

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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

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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%

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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

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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

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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

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8incomycin 4

.ash-eutropenia "hrombocytopenia

4rythema multiforme $rare%9seudomembranous colitis

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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

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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

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FARMAKOLOGI ANTIBIOTIK