antibiotics affecting bacterial growth by inhibiting protein synthesis.

1. ANAM MUNIR
LECTURER-FLS
LECTURE 6
INHIBITORS OF PROTEIN SYNTHESIS

2. • Other cell wall inhibiting antibiotics:
• Bacitracin (Bacillus, tracy :girl, against gram positive bacteria)
• Vancomycin (streptomyces: Against Staph, MRSA, VRE
:vancomycin resistant enterococci)
• Antimycobacterial antibiotics:
• Isoniazid:Mycobacterium tuberculosis
• Ethambutol: Mycobacteria,inhibts mycolic acid addition in cell
wall.
• Rifampin along with above two to cure Tuberculosis

3. INHIBITORS OF PROTEIN SYNTHESIS
1. Chloramphenicol
2. Aminoglycosides
3. Tetracycline
4. Glycylcyclins
5. Macrolides
6. Streptogramins
7. Oxazolidinoses
8. Pleuromutilins

4. CHLORAMPHENICOL
• Chloramphenicol inhibits the formation of peptide bonds in the
growing polypeptide chain by reacting with the 50S portion of the
70S prokaryotic ribosome.
• Because of its simple structure it is less expensive for the
pharmaceutical industry to synthesize it chemically than to isolate
it from Streptomyces. It is relatively inexpensive, and has a broad
spectrum, so chloramphenicol is often used where low cost is
essential.

5. CONTINUE….
• Its small molecular size promotes its diffusion into areas of the
body that are normally inaccessible to many other drugs.
• However, chloramphenicol has serious adverse effects; most
important is the suppression of bone marrow activity. This
suppression affects the formation of blood cells. In about 1 in
40,000 users, the drug appears to cause aplastic anemia, a
potentially fatal condition; the normal rate for this condition is
only about 1 in 500,000 individuals

6. DRUG OF CHOICE…
• Physicians are advised not to use the drug for trivial conditions
or ones for which suitable alternatives are available.
• Other antibiotics inhibiting protein synthesis by binding at the
same ribosomal site as chloramphenicol are clindamycin and
metronidazole .
• These three drugs are structurally unrelated, but all have
potent anaerobic activity. Clindamycin has a noted association
with Clostridium difficile-associated diarrhea Its effectiveness
against anaerobes has led to its use in the treatment of acne.

9. AMINOGLYCOSIDES
• Aminoglycosides Aminoglycosides are a group of antibiotics in
which amino sugars are linked by glycoside bonds.
• Aminoglycoside antibiotics, such as streptomycin and
gentamicin, interfere with the initial steps of protein synthesis
by changing the shape of the 30S portion of the 70S prokaryotic
ribosome. This interference causes the genetic code of the
mRNA to be read incorrectly. They were among the first
antibiotics to have significant activity against gram-negative
bacteria.
• Probably the best-known aminoglycoside is streptomycin, which
was discovered in 1944. Streptomycin is still used as an
alternative drug in the treatment of tuberculosis, but rapid
development of resistance and serious toxic effcxts have
diminished its usefulness.

10. AMINOGYCOSIDES
• Aminoglycosides can affect hearing by causing permanent
damage to the auditory nerve, and damage to the kidneys has
also been reported.
• As a result, their usc has been declining.
• Neomycin is present in many nonprescription topical
preparations. Gentamicin (spelled with an "i" to reflect its
source, the filamentous bacterium Micromonospora) is
especially useful against Pseudomonas infections.
• Pseudomonads are a major problem for persons suffering from
cystic fibrosis. The aminoglycoside tobramycin is administered
in an aerosol to help control infections that occur in patients
with cystic fibrosis.

12. TETRACYCLINS
• Tetracyclines Tetracyclines are a group of closely related broad-
spectrum antibiotics produced by Streptomyces spp. The
tetracyclines interfere with the attachment of the tRNA carrying
the amino acids to the ribosome at the 30S portion of the 70S
ribosome, preventing the addition of amino acids to the growing
polypeptide chain. They do not interfere with mammalian
ribosomes because they do not penetrate very well into intact
mammalian cells. However, at least small amounts are able to
enter the host cell, as is apparent from the fact that the
intracellular pathogenic rickettsias and chlamydias are sensitive
to tetracyclines.

13. • The selective toxicity of these drugs is due to a greater
sensitivity of the bacteria at the ribosomal level.
Tetracyclines not only are effective against gram-
positive and gram-negative bacteria but also penetrate
body tissues well and are especially valuable against
the intracellular rickettsias and chlamydias. Three of
the more commonly used tetracyclines are
oxytetracyclille (Terramycin), chlortetracycline
(Aureomycin), and tetracycline itself

14. • Some semisynthetic tetracyclines, such as doxycycline
and minocyclille, are available. They have the
advantage of longer retention in the body. A derivative
of minocycline that has a broad spectrum of activity is a
new class of antibiotics, the glycylcyclines. The first of
this class is tigecycline (Tygacil), which was developed
as a response to MRSA. Tetracyclines are used to treat
many urinary tract infections, mycoplasmal pneumonia,
and chlamydial and rickettsial infections.

15. • They are also frequently used as alternative drugs for such
diseases as syphilis and gonorrhea. Tetracyclines often
suppress the normal intestinal microbiota because of their
broad spectrum, causing gastrointestinal upsets and often
leading to superinfect ions, particularly by the fungus
Calldida albiC(l/lS. They are not advised for children, who
might experience a brownish discoloration of the teeth, or
for pregnant women, in whom they might cause liver
damage. Tetracyclines are among the most common
antibiotics added to animal feeds, where their use results in
significantly faster weight gain; however, some human
health problems can also result