antibakteri1
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ANTIBAKTERI
Dripa Sjabana, dr., [email protected]
Mata Ajar Farmakologi Prodi Pendidikan Dokter
Universitas Airlangga2006
(pengantar antibiotik & penghambat sintesis dinding sel bakteri)
St ruk t u r & Met abo l isme se lbak te r i
reaksitk.
I
reaksitk.
II
reaksitk.
III
PO43-
NH4+ SO4
2-
glukosa
Molekulprekursor
& ATP
heks
osam
in
Asamamino
nukleotida
peptidoglikan
protein
RNA
DNA
FolatAnalog pirimidin & purin
Sintesis proteinSintesis peptidoglikanSintesis asam nukleat
molekul konstituen
molekul makro
Modifikasi dari Katzung (2004)
Target K er ja An t ibak t e r i
I. Enzim sintesis dinding sel
II. Ribosom bakteri
III. Enzim sintesis nukleotida danreplikasi DNA
Ant ib io t i ka dengan Targe t Ker ja
Enzim Sintes is Dinding Sel
A. Beta laktam1. Penicillin2. Cephalosporin3. Monobactam4. Carbapenem5. Inhibitor beta-laktamase
(clavulanic acid, sulbactam, tazobactam)6. Vancomycin
B. TeicoplaninC. FosfomycinD. BacitracinE. Cycloserine
Outer membrane, lipidbilayer, is present ingram (-) but not gram(+).
The peptidoglycan is
much thicker in gram(+) than in gram (-).
Penicilin-bindingproteins (PBPs) aremembrane proteins thatcros-link peptidoglycan.
Beta-lactamase, ifpresent, reside in theperiplasmic space orthe outer surface of thecytoplasmic membran,when they may destroybeta-lactam antibioticsthat penetrate the outermembrane.
PBP
Katzung(2004)[email protected] 6
Bactoprenol (BP)is the lipidmembranecarrier
M=N-
acetylmuramicacid,Glc=glucose,NAcGlc or G= N-acetylglucosamine
1= fosfomycin,2= cycloserine,3=basitracin,4=vancomycin,5=beta-lactamantibiotics.
Katzung(2004)
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Figure 44.3 Schematic diagram of the biosynthesis of peptidoglycan in a bacterial cell (e.g. Staphylococcus aureus) with the sites of action of v arious antibiotics. Thehydrophilic disaccharide-pentapeptide is transferred across the lipid cell membrane attached to a large lipid (C55 lipid) by a pyrophosphate bridge (-P-P-). On the outside,it is enzymically attached to the 'acceptor' (the growing peptidoglycan layer). The final reaction is a transpeptidation, in which the loose end of the (gly)5 chain is attached
to a peptide side-chain of an M in the acceptor and during which the terminal amino acid (alanine) is lost. The lipid is regenerated by loss of a phosphate group (Pi)before functioning again as a carrier. (M, N-acetylmuramic acid; G, N-acetylglucosamine.)
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2005Elsevier [email protected] 8
t o f o rm a c ross l i nk f o r ce l l w a l l r i g id it y s t ruc tu re
transpeptidase
-lactam AB
inhibitor
Autolytic enzimes
bacterial lysisbacterial
bound to PBP
analog D-AlaD-Ala
Modifikasi dari Katzung (2004)
Figure 44.2 Schematic diagram of a single layer of peptidoglycanfrom a bacterial cell (e.g. Staphylococcus aureus) showing the site of action of the -lactamantibiotics( more detail in Fig. 44.3).In Staphylococc usaure usthe peptide cross-links consist of five glycine residues. Gram-positive bacteria have several layers of
peptidoglycan. (NAMA,N-acetylmuramic acid;NAG,N- acetylglucosamine.)
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2005Elsevier [email protected] 10
PENICILLINSubsituted 6-aminopenicillanic acid
CEPHALOSPORINSubsituted 7-aminocephslosporic acid
A = thiazolidine ring Katzung(2004)
MONOBACTAMSubsituted 3-amino-4-methylmonobactamic acid
CARBAPENEMSubsituted 3-hydroxyethylcarbapenemic acid
Katzung(2004)
Penic i l l in
Penicillin G (iv), VK (po)
Antistaphylococcus
Cloxacillin, dicloxacillin (po)
Nafcillin, oxacillin (iv)
Extended-spectrum
Amoxicillin, +clav (po)
Piperacillin (iv)
Ticarcillin (iv)
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Cephalosporin (1)
1st generation:
Cefadroxil, cefazolin, cephalexin, cepharpirin,cephradine
Very active againts gram(+) cocci.
2nd generation:
Cefaclor, cefamandole, cefonicid, cefuroxime,cefprozil, loracarbef, ceforanide,
cephamycins, cefoxitin, cefmetazole, cefotetan
Extended gram(-) coverage
Cephalosporin (2)
3rd generation:
Cefoperazone, cefotaxime, ceftazidime,ceftizoxime, ceftriaxone, cefixime, cefpodoximeproxetil, ceftibuten, moxalactam
Expanded gram(-) coverage, + bbb.
4th generation:
cefepime
More resistant to hydrolysis by chromosomalbeta-lactamases (eg. enterobacter) and someextended spectrum betalaktamases
Monobac tam
Aztreonam
Spektrum ~ aminoglycoside
Jelask an hubungan:
Sulphonamide
PABA
Folate
Bakteri vs. manusia ?
Jelask an hubungan:
Trimethoprim
Tetrahydrofolate Thymidylate
Dihydrofolate reductase
Bakteri vs. manusia ?
Bacaan lan ju t
Katzung BG ed.(2004). Farmakologi Dasar & Klinik, ed.8,buku 3. Jakarta: Salemba Medika, hal.3-33.
Rang HP et al. (2003). Pharmacology, ed.5.
London: Elsevier, p.620-643.
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