Download Broad spectrum drugs

‫االسبوع الثاني‬
Microbiology
ANTIBACTERIAL DRUGS
Importance of antimicrobial therapies is selective
toxicity: selective inhibition of the growth of
microorganisms
without damaging the host. So it should be very toxic to
the bacteria, but not/very little toxic to humans.
This is done by using the difference between metabolism
and structure of the microorganism + the features of the
human cell.
Major site of action for bacterial drugs:
1. Cell wall
2. Ribosomes
3. Nucleic acid
4. Cell membranes
Broad spectrum drugs: are active against several
types
of
organisms,
e.g.
cephalosporins,
aminoglycosides,
tetracyclins.
Narrow spectrum drugs: are active against one or
very few types of microorganisms, e.g. vancomycin
for
staphylococci and enterococci only.
Bactericidal drugs: kills the bacteria
Bacteriostatic drugs: inhibits the bacteria’s growth,
but doesn’t kill it.
Chemoprophylaxis drugs: are used to prevent
disease, e.g. penicillin and ampicillin. Used in 3
circumstances:
a) Prior to surgery
b) In immunocompromised patients
c) In people who have been exposed to an organism
When choosing a drug, one should be aware of: sufficient
therapeutic concentration, appropriate dosage and
timing.
Antibiotics with bactericidal effect:
1. Penicillin
2. Cephalosporins
3. Aminoglycosied
4. Fluroquinolons
Broad spectrum penicillin derivatives for both Gand G+:
1. Ampicillin
2. Amoxicillin
3. Piperacillin
4. Azlocillin
5. Mezlocillin
Microbiology Titles Negar Barazandeh
Basic Bacteriology, Parasitology, Mycology.
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2. Major groups of antibacterial drugs. Mechanism of
action of antibacterial drugs.
1. Inhibition of cell wall synthesis:
Penicillin
Binds to active site of transpeptidase and in this way
inhibits peptidoglycan synthesis (which is needed for the
cell’s
structural support).
Exposure to penicillin activates autolytic enzymes that
degrade the bacteria. If these autolytic enzymes are not
activated, the bacteria are not killed – seen in some
strains of Staphylococcus Aureus (said to be tolerant).
It kills bacteria when they are growing i.e. when they
are synthesizing new peptidoglycans. Penicillins are thus
more
effective/active during the log phase/exponential phase
than during lag phase.
Both penicillin and cephalosporin are ß-lactam drugs,
meaning an intact ß-lactam ring is needed for activity.
Without
it, they won’t work
Hypersensitivity to penicillin is a growing problem.
All penicillin family antibiotics have ß-lactam ring, this
is why they are called β-lactam antibiotics. Penicillin
passes through
channels in the cell wall called porin – then the ßlactam ring binds to and inhibits the transpeptidase
enzyme cell wall
synthesis gets arrested and the cell dies. So in order to
be effective, the β-lactam penicillin must:
a) Penetrate the cell layers
b) Keep its ß-lactam ring intact
c) Bind the transpeptidase
The purpose of using ß-lactamase inhibitors in
antibacterial therapy is that the combination of ßlactamase inhibitors (e.g.
clavulanic acid or sulbactam) with ß-lactamase
sensitive penicillins (e.g. amoxicillin or ampicillin) can
overcome resistance
mediated by many but not all lactamase.
Cephalosporins
Is structurally same as penicillin – both have ß-lactam
ring.
Inhibits cross-linking of peptidoglycan.
Has a broad range, well tolerated and fever
hypersensitivity reactions than penicillin.
First generation cephalosporins are mainly active
against G+ cocci, while 2nd, 3rd and 4th generation
cephalosporins
have expanded to also act against G+ rods.
Vancomycin
Is a glycopeptide – not a ß-lactamase.
It inhibits cell wall synthesis in G+ bacteria by
blocking transpeptidase.
2. Inhibition of protein synthesis:
Aminoglycosides
Acts on 30s subunit of bacteria.
It inhibits bacterial protein synthesis by binding to 30s
subunit, which blocks the initiation complex. No peptide
bonds
are formed and no polymerases are made.
Are a family of bactericidal drugs which include:
- Gentamicin
- Tobramycin
- Streptomycin
- Amikacin
Tetracyclines
Acts on 30s subunit of bacteria.
Inhibits bacterial protein synthesis by blocking the
binding of aminoacyl t-RNA to the 30s ribosomal
subunit.
Effective against both G+ and G-.
Chloramphenicol
Acts on 50s subunit.
Inhibits bacterial protein synthesis by blocking peptidyl
transferase the enzyme that adds new amino acids to
the
growing polypeptide.
Effective against G+, G- and anaerobes.
Erythromycin
Acts on 50s subunit
Inhibits bacterial protein synthesis by blocking the
release of the t-RNA after is has delivered its amino
acids to the
growing polypeptide.
Erythromycin is a member of the macrolides family.
Has wide spectrum of activity.
Clindamycin
Acts in the same way as erythromycin
Effective against many anaerobic bacteria