Protein synthesis inhibitors it is the part of antimicrobial agents or Chemotherapy.

1. PROTIEN SYNTHESIS
INHIBITORS
Presented by – Archita srivastava
M.pharm 1st year

2. CONTENT
 Protein synthesis
 Introduction of Protein synthesis inhibitors
 Pharmacology ofTetracycline
 Pharmacology of choramphenicol
 Pharmacology of Macrolides

3. Protein synthesis
 Amino acids are shown as numbered
circles. .
 In step 1, the charged tRNA unit carrying
amino acid 6 binds to the acceptor site on
the 70S ribosome.
 step 2.The peptidyl tRNA at the donor
site, with amino acids 1 through 5, then
binds the growing amino acid chain to
amino acid
 step 3 The uncharged tRNA left at the
donor site is released , and the new 6-amino
acid chain with its tRNA shifts to the
peptidyl site .

4. PROTEIN SYNTHESIS

5. PROTEIN SYNTHESIS INHIBITOR
 Protein synthesis takes place on the ribosomes. Eukaryotic and
prokaryotic ribosomes are different, and this provides the basis
for the selective antimicrobial action of some antibiotics.
 The bacterial ribosome consists of a 50s subunit and a 30s
subunit whereas in the mammalian ribosome the subunits are
60S and 40S .
 Bacteriostatic, protein-synthesis inhibitors that target the
ribosome such as tetracycline and chloramphenicol, macrolides
and ketolides, lincosamides (clindamycin), streptogramins
(quinupristin/dalfopristin), oxazolidinones (linezolid),and
aminocyclitols (spectinomycin).

6. TETRACYCLINE
 It is also called broad spectrum antibiotics.
 The tetracyclines are close congeners of polycyclic
naphthacenecarboxamide.
 Tetracyclines are bacteriostatic antibiotics with activity
against a wide range of aerobic and anaerobic gram-
positive and gram-negative bacteria.
 Classification –
1.chlortetracycline
2. oxytetracyline
3. demeclocyline
4. Doxycycline
5.Minocycline

7. Mode of action
 It is bacteriostatic
 Inhibit protein synthesis.
 Bind to 30s ribosome.

8. PHARMACOKINETICS
 Absorption: All tetracyclines are adequately
but incompletely absorbed after oral ingestion
However, taking these drugs concomitantly
with dairy foods in the diet decreases
absorption due to the formation of
nonabsorbable chelates of the tetracyclines
with calcium ions.
 Distribution: The tetracyclines concentrate in
the liver, kidney, spleen, and skin, and they
bind to tissues
 undergoing calcification (for example,
teeth and bones) or to tumors that have high
calcium content
 All tetracyclines cross the placental barrier
and concentrate in fetal bones and dentition..
ADMINISTRATIONAND FATE
OFTETRACYCLINES.

9. Typical therapeutic applications of
tetracyclines.

10. ADVERSE EFFECT

11. Resistance toTetracycline
 Resistance is primarily plasmid mediated and often inducible.
The three main resistance mechanisms are
 Decreased accumulation of tetracycline as a result of either
decreased antibiotic influx or acquisition of an energy-
dependent efflux pathway;
 Production of a ribosomal protection protein that displaces
tetracycline from its target, a “protection” that also may occur
by mutation.
 Enzymatic inactivation of tetracyclines.

12. Chloramphenicol
• Chloramphenicol, an antibiotic produced by Streptomyces venezuelae
• It is a yellowish white crystalline solid, aqueous solution is quite stable, stands
boiling, but needs protection from light.
• The nitrobenzene moiety of chloramphenicol is probably responsible for the
antibacterial activity as well as its intensely bitter taste.
• Chloramphenicol is rapidly and completely absorbed from the gastrointestinal tract
and is not affected by food ingestion or metal ions.

13. Mode of action
 Chloramphenicol inhibits bacterial
protein synthesis by interfering
with ‘transfer’ of the elongating
peptide chain to the newly attached
aminoacyl-tRNA at the ribosome-
mRNA complex. It specifically
attaches to the 50S ribosome near
the acceptor (A) site and prevents
peptide bond formation between
the newly attached aminoacid and
the nascent peptide chain

14. PHARMACOKINETICS
DRUG INTERACTION.
ADMINISTRATION AND
FATE OF
CHLORAMPHENICOL.

15. Resistance to Chloramphenicol.
 Resistance to chloramphenicol usually is caused by a plasmid-
encoded acetyltransferase that inactivates the drug. Resistance also
can result from decreased permeability and from ribosomal
mutation. Acetylated derivatives of chloramphenicol fail to bind to
bacterial ribosomes.

16. ADVERSE EFFECT
Gray baby syndrome

17. CLINICAL USE
 Chloramphenicol is used topically in the treatment of eye
infections because of its broad spectrum and its penetration of
ocular tissues and the aqueous humor. It is ineffective for
chlamydial infections.
 Chloramphenicol remains a major treatment of typhoid and
paratyphoid fever in developing countries.

19. MACROLIDES
 The macrolides are a group of closely related compounds
characterized by a macrocyclic lactone ring (usually containing 14
or 16 atoms) to which deoxy sugars are attached.
 Erythromycin was discovered in 1952 by McGuire and coworkers in
the metabolic products of a strain of Streptomyces erythreus.
 Clarithromycin and azithromycin are semisynthetic derivatives of
erythromycin.

20. Antimicrobial Activity.
 Erythromycin usually is bacteriostatic but may be bactericidal in high
concentrations against susceptible organisms.
 The antibiotic is most active in vitro against aerobic gram-positive cocci
and bacilli Staphylococci are considered susceptible at ≤0.5 μg/mL and
streptococci at ≤0.25 μg/mL.
 In addition, Campylobacter, Legionella, Branhamella catarrhalis,
Gardnerella vaginalis and Mycoplasma, that are not affected by penicillin,
are highly sensitive to erythromycin

21. MODE OF ACTION
 Macrolides bind to the 50S ribosomal
subunit of bacteria but not to the 80S
mammalian ribosome; this accounts for its
selective toxicity. Binding to the ribosome
occurs at a site near peptidyltransferase, with
a resultant inhibition of translocation,
peptide bond formation, and release of
oligopeptidyl tRNA.

22. Pharmacokinetics
 Erythromycin base is acid labile.
 To protect it from gastric acid, it is
given as enteric coated tablets, from
which absorption is incomplete and
food delays absorption by retarding
gastric emptying. Its acid stable
esters are better absorbed.
 Erythromycin is widely distributed
in the body, enters cells and into
abscesses, crosses serous
membranes and placenta, but not
bloodbrainbarrier.

23. ADVERSE EFFECT AND DRUG
INTEERACTION


24. Typical therapeutic applications of
macrolides.
• Erythromycin: This drug is effective against many of the same organisms as penicillin G
therefore, it is used in patients who are allergic to the penicillins.
• Atypical pneumonia caused by Mycoplasma pneumoniae: rate of recovery is hastened.
• Whooping cough: a 1–2 week course of erythromycin is the most effective treatment for
eradicating

25. REFERENCES
 1. The pharmacological basis of therapeutics – Goodman & Gillman’s
12th edition page no. 1521-1545.
 2. Basic and clinical pharmacology by katzung B. G 12th edition page
no. 810-845.
 3. K.D Tripathi , Essential of medical pharmacology 7th edition page
no. 733
 4. Lippincott’s Illustrated review , Pharmacology 4th edition page no.
596-613.
 5. Modern Pharmacology with clinical applications Charles R. Craig
Robert E. Stitzel 5th edition page no. 550-556