protein synthesis inhibitors by jitendra bhangale
DESCRIPTION
Tetracyclines and ChloramphenicolTRANSCRIPT
8/5/2012
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© 2010 Delmar, Cengage Learning1
By- Jitendra Bhangale
Assistant Professor & Head,
Department of Pharmacology,
Smt N. M. Padalia Pharmacy College,
Ahmedabad
© 2010 Delmar, Cengage Learning2
By Jitendra BhangaleAsst. Prof. Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, Ahmedabad
8/5/2012
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© 2010 Delmar, Cengage Learning3
By Jitendra BhangaleAsst. Prof. Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, Ahmedabad
It was originally obtained from the soil actinomycetes.
© 2010 Delmar, Cengage Learning4
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 availableBy Jitendra Bhangale
Asst. Prof. Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, Ahmedabad
8/5/2012
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© 2010 Delmar, Cengage Learning5
By Jitendra BhangaleAsst. Prof. Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, Ahmedabad
The peptidyl tRNA at thedonor site donates the growingpeptide chain to the aminoacyltRNA at the acceptor site in areaction catalyzed by peptidyltransferase.
The tRNA, discharged of itspeptide, is released from thedonor site to make way fortranslocation of the newlyformed peptidyl tRNA.
The acceptor site is then freeto be occupied by the next"charged" aminoacyl tRNA.
© 2010 Delmar, Cengage Learning6
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.
By Jitendra BhangaleAsst. Prof. Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, Ahmedabad
8/5/2012
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© 2010 Delmar, Cengage Learning7
Cocci
N. gonorrhoea
N. Meningitidis
Gram-positive bacilli
Clostridia
Listeria,
Corynebacterta,
Propionibacterium acnesB. Anthracis
By Jitendra BhangaleAsst. Prof. Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, Ahmedabad
It is a broad spectrum antibiotic that active against many gram-
positive and gram-negative bacteria
Gram-negative bacilliH. ducreyi,CalymmatobacteriumGranulomatisV. cholerae,Yersinia pestis,Y. enterocoliticaCampylobacter,Helicobacter pylori,Brucella,F. tularensis
© 2010 Delmar, Cengage Learning8
By Jitendra BhangaleAsst. Prof. Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, Ahmedabad
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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© 2010 Delmar, Cengage Learning9
By Jitendra BhangaleAsst. Prof. Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, Ahmedabad
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.
© 2010 Delmar, Cengage Learning10
By Jitendra BhangaleAsst. Prof. Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, Ahmedabad
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
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© 2010 Delmar, Cengage Learning11
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 ofdemeclocycline, can induce sensitivity to sunlight orultraviolet light, particularly in fair-skinned persons.
Vestibular Reactions:- Dizziness, vertigo, nausea, and vomitinghave been particularly noted with doxycycline at doses above100 mg.
By Jitendra BhangaleAsst. Prof. Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, Ahmedabad
© 2010 Delmar, Cengage Learning12
By Jitendra BhangaleAsst. Prof. Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, Ahmedabad
8/5/2012
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© 2010 Delmar, Cengage Learning13
By Jitendra BhangaleAsst. Prof. Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, Ahmedabad
It was originally obtained from the Streptomyces venezuelae 1947.
© 2010 Delmar, Cengage Learning14
By Jitendra BhangaleAsst. Prof. Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, Ahmedabad
The peptidyl tRNA at thedonor site donates the growingpeptide chain to the aminoacyltRNA at the acceptor site in areaction catalyzed by peptidyltransferase.
The tRNA, discharged of itspeptide, is released from thedonor site to make way fortranslocation of the newlyformed peptidyl tRNA.
The acceptor site is then freeto be occupied by the next"charged" aminoacyl tRNA.
8/5/2012
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© 2010 Delmar, Cengage Learning15
Chloramphenicol binds to the50S ribosomal subunit at thepeptidyltransferase site andinhibits the transpeptidationreaction.
Chloramphenicol binds to the50S ribosomal subunit near thesite of action of clindamycinand the macrolide antibiotics.
These agents interfere withthe binding of chloramphenicoland thus may interfere witheach other's actions if givenconcurrently.
By Jitendra BhangaleAsst. Prof. Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, Ahmedabad
© 2010 Delmar, Cengage Learning16
H. influenzae,
Neisseria meningitidis,
S. pneumoniae
Enterobacteriaceae
V. cholerae
By Jitendra BhangaleAsst. Prof. Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, Ahmedabad
It is a broad spectrum antibiotic that active against many gram-
positive and gram-negative bacteria
Salmonella typhi
Escherichia coli
Klebsiella pneumoniae
Proteus mirabilis
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© 2010 Delmar, Cengage Learning17
By Jitendra BhangaleAsst. Prof. Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, Ahmedabad
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.
© 2010 Delmar, Cengage Learning18
By Jitendra BhangaleAsst. Prof. Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, Ahmedabad
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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© 2010 Delmar, Cengage Learning19
By Jitendra BhangaleAsst. Prof. Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, Ahmedabad
Distribution:- Chloramphenicol is widely distributed in the
body.
Excretion:- Chloramphenicol is primarily excreted in urine by
glomerular filtration.
© 2010 Delmar, Cengage Learning20
Typhoid Fever
Bacterial Meningitis
Anaerobic Infections
Rickettsial Diseases
Brucellosis
By Jitendra BhangaleAsst. Prof. Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, Ahmedabad
8/5/2012
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© 2010 Delmar, Cengage Learning21
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
By Jitendra BhangaleAsst. Prof. Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, Ahmedabad
© 2010 Delmar, Cengage Learning22
By Jitendra BhangaleAsst. Prof. Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, Ahmedabad