INHIBITOR OF CELL

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

INHIBITOR OF CELL WALL

SYNTHESIS

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

in different strains, determine antigenicity of

m.o
endotoxins inflamm reactions, fever, etc
porins hydrophylic A.M can move freely

 Difficulty to penetrate complex outer

layer reasons why some A.M are less
effective against gram (-) m.o than against
gram (+)

LPS of cell wall is a major barrier to

penetration for:
penicillin G
methicillin
vancomycin
rifampicin

Inhibitor of cell wall synthesis

Beta Lactam ( = BL ) AM:

- 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 only

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

3. Extended spectrum penicillin

> ampicillin, amoxillin
> (+) B-lactamase inhibitor (clavulanic acid or sulbactam)

4. Anti pseudomonas penicillin

5. Penicillin + AMG
> has synergitic effect
Broader spectra

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:

1. A to gastric acid and severity of infections

p.o, iv, im, i.t, depot (PP-G, BP-G)

Empty stomach (ampi), amox ()

2. D:

Cross PBB BUT non-teratogenic

Do not Cross BBB Except in inflammed

meningens

3. M & E

Through kidney (tubular secretion)

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

better activity against gr (+)

improved activity against gr (+)

more resistant to B-lactamase

Cephalosporins
PK:

1. A most of all must be given iv (poor oral

absorption)

p.o: cefalexin, cefuroxime

2. D:

Cross BBB for 3rd generation

3. M & E

Through kidney (tubular secretion)

Ceftriaxone & cefoperazone bile

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)

Other inhibitor of Cell wall

synthesis
A.
Vancomycin:

A glycopeptide, effective for MRSA

BUT now: emerging of resistance to
Vancomycin
M.O.A: inhibit synthesis of phospholipids
A.M spectrum: serious infection only

Allergic to B-lactam;, AB-associated collitis

(p.o)

PK: slow iv ; renal excretion

AEs is a serious problem (fever, phlebitis,
hearing loss, shock, redman syndrome)

Other inhibitor of Cell wall

synthesis
B.
Bacitracin:
Very toxic for systemic

So..only to topical application

Effective for gram (+) m.o