Protein synthesis inhibitors

8/6/2012

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

1

8/6/2012

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

2

8/6/2012

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.


3

8/6/2012

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.

4

8/6/2012

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

5

8/6/2012

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.
11

12

6

8/6/2012

It was originally obtained from the Streptomyces venezuelae 1947.

13

transferase.



14

7

8/6/2012

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.

15


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

16

8

8/6/2012

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.

17

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.

18

9

8/6/2012

Distribution:- Chloramphenicol is widely distributed in the

body.

Excretion:- Chloramphenicol is primarily excreted in urine by

glomerular filtration.

19

Typhoid Fever

Bacterial Meningitis

Anaerobic Infections

Rickettsial Diseases

Brucellosis

20

10

8/6/2012


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

21

22

11

8/6/2012

Macrolide antibiotics contain a
many-membered lactone ring
(14-membered rings for
erythromycin & clarithromycin
and a 15-membered ring for
azithromycin)
to which are attached one or
more deoxy sugars.

23

Narrow spectrum

Erythromycin (Streptomyces erythreus)

Broad spectrum

Clarithromycin,

Roxithromycin

Azithromycin are semisynthetic derivatives of

erythromycin

24

12

8/6/2012

transferase.



25

Macrolide antibiotics are
bacteriostatic agents that inhibit
protein synthesis by binding
reversibly to the 50S ribosomal
subunits of sensitive organisms.
Erythromycin appears to inhibit
the translocation step wherein the
nascent peptide chain temporarily
residing at the A site of the
transferase reaction fails to move to
the P, or donor, site.
Alternatively, macrolides may
bind and cause a conformational
change that terminates protein
synthesis by indirectly interfering
with transpeptidation and
translocation.
26

13

8/6/2012


Gram-positive organisms Listeria
Pneumococci
Streptococci Mycobacterium kansasii
Staphylococci
Corynebacteria Mycobacterium scrofulaceum
Mycoplasma
Legionella Bordetella pertussis
Chlamydia trachomatis
C psittaci Bartonella henselae
C pneumoniae
Helicobacter B quintana
27

Absorption:-

Erythromycin base is destroyed by stomach acid and must be

administered with enteric coating.

Food interferes with absorption. Stearates and esters are fairly

acid-resistant and somewhat better absorbed.

Distribution:- Erythromycin are widely distributed in the body.

Excretion:- Erythromycin are primarily excreted in urine.

28

14

8/6/2012


Gastrointestinal effects:- Nausea, vomiting, and diarrhoea

Hepatitis with cholestatic jaundice

29

Mycoplasma pneumoniae
Staphylococcal Infections
Infections
Campylobacter Infections
Legionnaires' Disease
Helicobacter pylori Infection
Chlamydial Infections
Tetanus
Diphtheria
Syphilis
Pertussis
Mycobacterial Infections
Streptococcal Infections

30

15

8/6/2012

31

16

Protein synthesis inhibitors

Recomendados

Recomendados

Mais conteúdo relacionado

Semelhante a Protein synthesis inhibitors

Semelhante a Protein synthesis inhibitors (9)

Último

Último (20)

Protein synthesis inhibitors