This document discusses two classes of protein synthesis inhibitors - tetracyclines and chloramphenicol. It provides details on their mechanisms of action, classifications, spectra of activity, pharmacokinetics, clinical uses, resistance, side effects and interactions. Tetracyclines are classified based on source and duration of action. They inhibit bacterial protein synthesis by binding to the 30S ribosomal subunit. Chloramphenicol also inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit. Both classes have broad-spectrum activity and are associated with various side effects.

1. BY MUNKWASE GRANT
DEPARTMENT OF PHARMACOLOGY
TETRACYCLINES &
CHLORAMPENICOL

2. Introduction
 One of the mechanisms of action for
antimicrobial agents is inhibition of protein
synthesis
 Protein synthesis is inhibited at the step of
translation in the ribosomes
 Protein synthesis inhibitors include
aminogycosides, Tetracyclines, Macrolides,
Clindamycin, oxazolidinones,Chloramphenicol, &
Streptogramins
 Protein synthesis inhibitors are mainly
bacteriostatic except aminogycosides

4. Protein synthesis inhibitors

6. TETRACYCLINES
Are classified in two ways
1. According to source
 Natural
 Semi synthetic
2. According to duration of action
 Short acting(half life is 6-8hrs)
 Intermediate(halflife is 12hrs)
 Long acting(halflife is >16hrs)

7. Classification by source
Natural
 Chlortetracycline
 Oxytetracycline
 Demeclocycline
Semi synthetic
 Doxycycline
 Tetracycline
 Minocycline
 Lymecycline
 Methacycline
 Rolitetracycline
 Tigecycline

8. Classification by duration of
action
Short acting Intermediate acting Long acting
•Tetracycline
•Oxytetracycline
•chlortetracycline
•Demeclocycline
•Methacycline
•Doxycycline
•Minocycline
•Tigecycline

9. Mechanism of action
 Inhibits protein synthesis
 Binds reversibly to the 30s subunit of the
ribosome
 inhibit amino acid incorporation by blocking the
attachment of aminoacyl tRNA to the
“A”(acceptor) site
 Bacteriostatic

10. Pharmacokinetics
 Free tetracyclines are crystalline amphoteric
substances of low solubility.
 They are available as hydrochlorides, which are
more soluble
 Variable absorption following oral administration
 30% for chlortetracycline
 60-70% for tetracycline, Oxytetracycline,
Methacycline
 95-100% for Doxycycline and Minocycline
 Tigecycline is poorly absorbed orally & must be
administered IV.

11. Pharmacokinetics
Absorption occurs mainly in the upper small
intestine
Absorption is impaired by;
 food (except Doxycycline and Minocycline)
 divalent cations (Ca2+, Mg2+, Fe2+) or Al3+
 dairy products and antacids
 alkaline pH
Tetracyclines are 40-80% bound by serum proteins

12. Pharmacokinetics
 Tetracyclines are distributed widely to tissues and
body fluids except for cerebrospinal fluid
 Tetracyclines cross the placenta to reach the
fetus and are also excreted in milk
 Tetracyclines are excreted mainly in bile and urine
but also in feaces to a small extent
 Doxycycline and Tigecycline eliminated by
nonrenal mechanisms

13. Spectrum of activity:
Tetracyclines are broad-spectrum antibiotics.
They are active against the following
microorganisms:
 gram-positive and gram-negative bacteria
 Spirochetes
 mycoplasmas
 rickettsiae

14. Spectrum of activity
 Mycoplasma pneumoniae
 Chlamydia trachomatis
 Borrelia recurrentis.
 Yersinia pestis
 Vibrio cholerae
 Campylobacter fetus
 Brucella species
 Streptococcus pneumoniee.
 Neisserie gonorrhoeae
 Helicobacter pylori

15. Resistance to tetracyclines
 Impaired influx or increased efflux by an active
transport protein pump
 Ribosomal protection
 Enzymatic inactivation.
 Most organisms resistant to tetracyclines are
susceptible to Tigecycline(not a substrate for
efflux pump) except proteus and pseudomonas
aeruginosa

16. Clinical uses of tetracyclines
 Drug of choice in infections with Mycoplasma
pneumoniae, Chlamydia, rickettsiae, and some
spirochetes
 Various gram-positive and gram-negative
bacterial infections
 Used in combination regimens to treat gastric and
duodenal ulcer disease caused by Helicobacter
pylori.
 Indicated for plague, tularemia, and brucellosis
 Treatment of acne
 Treatment of protozoal infections including
p.falciparum

17. Side effects of tetracyclines
 GIT irritation ( reduced by coadministration of
food)
 Photosensitivity
 Hepatotoxicity and renal toxicity
 Permanent brown discoloration of teeth( do not
use in children less than 8years)
 Depress bone growth in infants
 Hypersensitivity reactions(e.g
angioedema,anaphylaxis,urticaria etc)

18. Major drug interaction of
tetracyclines::
Antacids containing aluminum,
calcium, or magnesium, and
iron-containing preparations
Impair the Absorption of
tetracyclines
Anticoagulant therapy Tetracyclines have been shown
to depress plasma prothrombin
activity, patients who are on
anticoagulant therapy may
require downward adjustment of
their anticoagulant dosage.
Bactericidal drugs Interfere with the bactericidal
action of penicillin, it is
advisable to avoid giving
tetracycline-class drugs in
conjunction with penicillin.

19. CHLORAMPHENICOL

20. Mechanism of action
Inhibits protein synthesis
Binds reversibly to 50 s subunit of ribosome
Block transpeptidation by inhibiting peptidyl
transferase
Broad spectrum bacteriostatic antimicrobial
Antibacterial activity
H. Influenza S. typhi
N. Meningitidis E. coli
S. Pneumoniae V.cholera
Rickettsiae Anaerobes- clostridium & B.
fragilis
CHLORAMPHENICOL

21. Pharmacokinetics
 Crystaline chloramphenicol is neutral, stable,
soluble in alcohol but poorly soluble in water
 Chloramphenicol succinate(prodrug) given
parenteraly is highly water-soluble
 Rapidly & completely absorbed from GIT
 About 50 % protein bound
 Metabolized mainly by liver through glucuronide
conjugation but may also under go reduction
 Well distributed, including CNS and CSF
 Excreted largely in urine. To a small extent in bile and
feaces

22. Resistance
 Production of chloramphenicol acetyltransferase
that inactivates the drug(major)
 Ribosomal mutation
 Decreased permeability

23. Clinical uses
Use limited because of potential toxicities
1. Typhoid fever- s. typhi ( quinolones are
preffered)
2. Meningitis –
H.influenzae,N.meningitidis,S.pneumoniae
( Ceftriaxone is preffered )
3. Anaerobic infections- B. fragilis (Metronidazole is
the drug of choice)
4. Rickettsial infections – Doxycycline is preffered
5. Bacterial conjunctivitis ( topical )

24. Side effects & interactions
1. Hypersensitivity- low incidence
2. Dose related and reversible bone marrow
suppression
3. A plastic anaemia ( fatal and irreversible)
4. Grey baby syndrome
5. Suprainfections
Interaction with other drugs
 Inhibits liver microsomal enzymes
Phenytoin
Tolbutamide
Chlorpropamide
Anticoagulants
 Chloramphenicol can antagonize bactericidal drugs

25. THANK YOU
END