Protein synthesis inhibitors by JITENDRA BHANGALE

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


By Jitendra BhangaleAsst. Prof. Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, Ahmedabad

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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 availableBy Jitendra Bhangale

Asst. Prof. Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, Ahmedabad

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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.


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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Cocci

N. gonorrhoea

N. Meningitidis

Gram-positive bacilli

Clostridia

Listeria,

Corynebacterta,

Propionibacterium acnesB. Anthracis


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



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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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

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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.




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It was originally obtained from the Streptomyces venezuelae 1947.



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.

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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.



H. influenzae,

Neisseria meningitidis,

S. pneumoniae

Enterobacteriaceae

V. cholerae


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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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.



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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Distribution:- Chloramphenicol is widely distributed in the

body.

Excretion:- Chloramphenicol is primarily excreted in urine by

glomerular filtration.


Typhoid Fever

Bacterial Meningitis

Anaerobic Infections

Rickettsial Diseases

Brucellosis


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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




Protein synthesis inhibitors by JITENDRA BHANGALE

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