TETRACYCLINES

BY: RASHMI KHANIJAU

LECTURE:08(29-04-2020)
UNIT:II (TETRACYCLINES)
 CONTENTS
1.INTRODUCTION
2. ANTIMICROBIAL SPECTRUM
3. CLASSIFICATION
4. MECHANISM OF ACTION
5. ADVERSE EFFECTS
6. USES
7. RESISTANCE
 1.INTRODUCTION
These are a class of antibiotics having a nucleus of four
cyclic rings.
First tetracyclin was introduced in 1948
Bacteriostatic
Broad-spectrum antibiotics
They inhibit protein synthesis
Obtained from soil actinomycetes.
All tetracyclines are slightly bitter solids
Aqueous solutions are unstable.
It contrasted markedly from penicillin and streptomycin
( the other two antibiotics available at that time) in
being active orally and in affecting a wide range of
microorganisms-hence called ‘broad spectrum-
antibiotic.
In gram-negative bacteria tetracyclines diffuse through
porin channels.
2. ANTIMICROBIAL SPECTRUM
When originally introduced, tetracyclines
inhibited practically all types of pathogenic
microorganisms except fungi and viruses.
1. Cocci: All gram-positive and gram-
negative cocci were originally sensitive.
2. Most gram-positive bacilli
3. Sensitive gram-negative bacilli
4. spirochetes
5. All rickettsiae and chlamydiae
6. Mycoplasma
7. Protozoa
 3. CLASSIFICATION
This class has following members
1. Tetracycline
2. Oxytetracycline
3. De-methyl-chlor-tetracycline
(demeclocycline)
4. Doxycycline
5. Minocycline
6. Tigecycline
4. MECHANISM OF ACTION
Tetracyclines inhibit protein synthesis by binding to 30S
ribosomes in susceptible organism.
Ribosomes are the protein factory(Kitchen) of the organisms
where proteins are synthesize .
Ribosomes have two sub-units:
 1. Smaller sub-unit (30 S)
 2. Larger sub-unit (50 S)
50 S sub-unit has two sites 1. Peptidyl (P) 2. Acceptor (A)
Protein synthesis is start from 30 S sub-unit by the m-RNA.
The initiation complex of mRNA starts protein synthesis and
polysome formation.
When nacent peptide chain is formed it will transported to the
(p)-site of 50 S ribosome.
Next amino-acid is transported to the acceptor (A) site of the
ribosome by its specific tRNA.
Tetracycline binds to 30S ribosome and inhibit aminoacyl tRNA
attachment to the ‘A’ site.
4. MECHANISM OF ACTION
 5. ADVERSE EFFECTS
1.Irritative effects
2. Organ toxicity
 Liver damage
 Kidney damage
 Phototoxicity
 Teeth and bones (Chelate gets deposited )
 Anti-anabolic effect
 increased intra cranial pressure
 Diabetes insipidus
 Vestibular toxicity
3. Hypersensitivity
4. Super infection
5. Superinfection
 6. USES
1. Empirical therapy: TC are often employed when the nature
and sensitivity of the infecting organism cannot be
reasonably gussed.
2. TC are the first choice of drugs:
i. Atypical pneumonia
ii. Cholera
iii. Brucellosis
iv. Plague
v. Rickettsial infections
3. TC are the second choice of drugs:
○i. To penicillins for tetanus, anthrax
○Ii. To ceftriaxone for gonorrhoea
○Ii. To ceftriaxone for syphilis in patients allergic to penicillin
4. other situations in which TC may be used are:
○i. Amoebiasis
○UTI
○Adjuvant to quinine
 7. RESISTANCE
Incomplete cross resistance is seen among
different members of tetracycline group.
Resistance develops slowly in a graded
manner
1. tetracycline concentrating mechanism
becomes less efficient
2. bacteria acquire capacity to pump it out
3. Plasma mediated synthesis of a
‘protection’ protein which protects the
ribosomal binding site from tetracycline.