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Inhibitor of Cell Wall Synthesis
Inhibitor of Cell Wall Synthesis
Inhibitor of Cell Wall Synthesis
WALL SYNTHESIS
1
2
Dwi
Dwi Indria
Indria Anggraini
Anggraini1,, Rovina
Rovina Ruslami
Ruslami2
1
Dept.
1
Dept. Pharmacology
Pharmacology Faculty
Faculty of
of Medicine,
Medicine, Lampung
Lampung
University;
University;
2
Dept.
2
Dept. Pharmacology
Pharmacology Faculty
Faculty of
of Medicine,
Medicine, Padjajaran
Padjajaran
University
University
Overview
INTRODUCTION:
M.O is classified as gram (+) or (-) gram
staining
BUT: not that simple; difference in structure
of cell wall
Periplasmic space
contain enzymes & other component
Peptidoglycan layer
forming 5% of cell wall
Outer membrane
contain protein molecules and lipoprotein that
linked to peptidoglycan
Complex polysaccharide
- Penicillins
- Cephalosporins
- Carbapenems
- Monobactams
Others Glycopeptides
Structure:
Thiazolidine
ring
B-lactam ring
B-lactam ring
Thiazolidine ring
B-lactam ring
Thiazolidine ring susbtituent
are added in R1, 2 or 3
B-lactam ring
Thiazolidine ring:
S was replaced by C
PENICILLIN:
1928: Alexander Flemming
Staph + penicillium growth of staph was
inhibited
Extraction of the substance
1941: Tested to pts with septicemia
5 days improved well
Nowits widely used, very effective
BUT..destroyed by B-lactamase & amidase
Structure:
Penicillin
M.O.A:
inhibit synthesis of cell wall peptidoglycan
bind to P-BP of bacteria inhibit transpeptidase
inactivation of an inhibitor autolytic enzymes in cell
wall lysis of bacterium
Penicillin
Penicillin
Types & AM activity:
1. Natural penicillin: Pen-G and Pen-V
2. Anti satph penicillin
> Stable to penicillinase
Penicillin
Resistance:
1. Natural have no peptidoglycan or cell wall that
impermiable to the drugs
2. Acquired (by plasmid)
a. Produce B-lactamase destroy the drug
permeability to drug D cant reach P-BP
c. Altered P-BP
Penicillin
PK:
2. D:
3. M & E
Penicillin
Clinical Use:
1. Are given p.o unless severe infection
2. Uses include:
Bacterial meningitis
Bone & joint infection
Skin & soft tissue infection
URTI, UTI (including GO),
Endocarditis, etc
3. Empirical, emerge of drug resistance !!
Penicillin
Cephalosporins
Introduction:
Penicillin Cephalosporin:
chemically, m.o.a, & toxicity
> stable to B-lactamase
broader spectrum of activity
Cephalosporin classification:
4 generation (~ spectrum AM activity)
against gr(+)
also against gr(-)
1st
2nd
3rd
4th
Cephadroxil
Cephalexin
Cephazolin
Cefuroxime
Cefoxitin
Cefotaxime
Ceftazidime
Ceftriaxone
Cefepime
Cefoperazone
Cefepime
Cephalosporins
PK:
2. D:
3. M & E
Other B-lactam AM
A. Carbapenems :
Imipenem, meropenem, ertapenem
Very broad spectrum (aerobic (gr (+),
(-),anaerobic)
Resistant to B-lactamase
PK: iv, renal excretions
AEs: nausea, vomit, diarrhea
Other B-lactam AM
B. Monobactams :
Has only B-lactam ring (exp: aztreonam)
Narrow spectrum (gr (-) cant for
empirical th/
Resistant to B-lactamase
PK: iv and im, renal excretions
AEs: non toxic, little cross-sensitivity
allergic
(alternative for pts who allergic to
penicillin)