Protein synthesis inhibitors by JITENDRA BHANGALE

8/5/2012

By- Jitendra Bhangale
Assistant Professor & Head,
Department of Pharmacology,
Smt N. M. Padalia Pharmacy College,
Ahmedabad
1
© 2010 Delmar, Cengage Learning

By Jitendra Bhangale
Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad2
© 2010 Smt N. M. Padalia

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8/5/2012

It was originally obtained from the soil actinomycetes.


Oxytetracycline is a natural product elaborated by
Streptomyces rimosus.
Tetracycline is a semisynthetic derivative of
chlortetracycline.
Demeclocycline is the product of a mutant strain of Strep.
aureofaciens
Methacycline, doxycycline, and minocycline all are
semisynthetic derivatives.
The Tetracyclines are close congeners of polycyclic
naphthacenecarboxamide.
Many others like Chlortetracycline, Methacycline, Rolitetracycline,
Lymecycline are no longer commercially available

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8/5/2012

The peptidyl tRNA at the
donor site donates the growing
peptide chain to the aminoacyl
tRNA at the acceptor site in a
reaction catalyzed by peptidyl
transferase.

The tRNA, discharged of its
peptide, is released from the
donor site to make way for
translocation of the newly
formed peptidyl tRNA.

The acceptor site is then free
to be occupied by the next
"charged" aminoacyl tRNA.


The tetracyclines are primarily
bacteriostatic; inhibit protein
synthesis by binding to 30S
ribosomes in susceptible
organism.

Inhibit aminoaceyl tRNA
attachment to A site

As a result the peptide chain
fails to grow.


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8/5/2012

It is a broad spectrum antibiotic that active against many gram-
positive and gram-negative bacteria

Cocci Gram-negative bacilli
H. ducreyi,
N. gonorrhoea Calymmatobacterium
N. Meningitidis Granulomatis
Gram-positive bacilli V. cholerae,
Clostridia Yersinia pestis,
Y. enterocolitica
Listeria, Campylobacter,
Corynebacterta, Helicobacter pylori,
Propionibacterium acnes Brucella,
B. Anthracis F. tularensis


Spirochetes, including T. pallidum and Borreha are ouite
sensitive.

All rickettsiae (typhus, etc.) and chlamydiae are highly sensitive.

Mycoplasma and Actinomyces are moderately sensitive.

Entamoeba histolytica and Plasmodia are inhibited at high
concentrations.

Resistance microorganisms

Notable bacilli that are not inhibited are Pseudomonas
aeruginosa, Proteus, Klebsiella, Salmonella typhi and many
Bact. fragilis.

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8/5/2012

Absorption:-
Absorption after oral administration is approximately
30% for chlortetracycline;
60–70% for tetracycline, oxytetracycline, demeclocycline,
and methacycline;
95–100% for doxycycline and minocycline.
Absorption occurs mainly in the upper small intestine and is
impaired by food (except doxycycline and minocycline); by
divalent cations (Ca2+, Mg2+, Fe2+) or Al3+; by dairy
products and antacids, which contain multivalent cations;
and by alkaline pH.

Distribution:- Tetracyclines are widely distributed in the body.
Excretion:- Most tetracyclines are primarily excreted in urine by
glomerular filtration.
Tetracyclines are classified as
1. Short-acting (chlortetracycline, tetracycline, oxytetracycline)
serum half-lives of 6–8 hours
2. Intermediate-acting (demeclocycline and methacycline)
serum half-lives of 12 hours
3. Long-acting (doxycycline and minocycline)
serum half-lives 16–18 hours

10
Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad

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8/5/2012

Hypersensitivity reactions (drug fever, skin rashes)
Gastrointestinal effects:- Nausea, vomiting, and diarrhoea
Bony Structures and Teeth
Liver Toxicity
Kidney Toxicity
Local Tissue Toxicity
Photosensitization
Systemic tetracycline administration, especially of
demeclocycline, can induce sensitivity to sunlight or
ultraviolet light, particularly in fair-skinned persons.
Vestibular Reactions:- Dizziness, vertigo, nausea, and vomiting
have been particularly noted with doxycycline at doses above
100 mg.
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8/5/2012

It was originally obtained from the Streptomyces venezuelae 1947.

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The peptidyl tRNA at the
donor site donates the growing
peptide chain to the aminoacyl
tRNA at the acceptor site in a
reaction catalyzed by peptidyl
transferase.

The tRNA, discharged of its
peptide, is released from the
donor site to make way for
translocation of the newly
formed peptidyl tRNA.

The acceptor site is then free
to be occupied by the next
"charged" aminoacyl tRNA.

14

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8/5/2012

Chloramphenicol binds to the
50S ribosomal subunit at the
peptidyltransferase site and
inhibits the transpeptidation
reaction.

Chloramphenicol binds to the
50S ribosomal subunit near the
site of action of clindamycin
and the macrolide antibiotics.

These agents interfere with
the binding of chloramphenicol
and thus may interfere with
each other's actions if given
concurrently.

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It is a broad spectrum antibiotic that active against many gram-
positive and gram-negative bacteria

H. influenzae, Salmonella typhi
Neisseria meningitidis,
Escherichia coli
S. pneumoniae
Klebsiella pneumoniae
Enterobacteriaceae
Proteus mirabilis
V. cholerae

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8/5/2012

Resistance mechanism

Resistance to chloramphenicol usually is caused by a plasmid-

encoded acetyltransferase that inactivates the drug.

Acetylated derivatives of chloramphenicol fail to bind to bacterial

ribosomes.

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Absorption:-

Chloramphenicol is absorbed rapidly from the

gastrointestinal tract.

Chloramphenicol succinate in plasma are achieved after

intravenous and intramuscular administration.

Chloramphenicol palmitate is a prodrug that is

hydrolyzed in the intestine to yield free

chloramphenicol.

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8/5/2012

Distribution:- Chloramphenicol is widely distributed in the

body.

Excretion:- Chloramphenicol is primarily excreted in urine by

glomerular filtration.

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Typhoid Fever

Bacterial Meningitis

Anaerobic Infections

Rickettsial Diseases

Brucellosis

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8/5/2012

Hypersensitivity reactions (drug fever, skin rashes)

Bone marrow depression

Vestibular Reactions:- Dizziness, vertigo, nausea, and vomiting

Gray baby syndrome: - The baby stopped feeding, vomited,
became hypotonic and hypothermic, abdomen distended,
respiration became irregular; an ashen gray cyanosis
developed in many, followed by cardiovascular collapse and
death.

Blood lactic acid was raised

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