fad

1. PROTEIN SYNTHESIS
INHIBITORS
Dr. Muhammad Fahd Mushtaq
M.Phil pharmacology (GCUF)

3. Tetracyclines
Mechanism of action

4. Resistance
• 1) impaired influx or increased efflux by an active transport
• protein pump
• (2) ribosome protection due to production of proteins that interfere
with tetracycline binding to the ribosome; and
• (3) enzymatic inactivation.
Clinical Uses
Empirical therapy, Tetracyclines are the first choice drug (Venereal
diseases, Lymphogranuloma venereum, Granuloma inguinale,
Atypical pneumonia, Cholera, Brucellosis, Plague, Relapsing fever

5. Adverse effects
Irritative effects, Organ toxicity, Phototoxicity, Teeth and bones, Antianabolic
effect, Increased intracranial pressure, Diabetes insipidus, Vestibular toxicity,
Superinfection, Hypersensitivity.

6. Aminoglycosides
Mechanism of Action
• Susceptible gram-negative organisms allow aminoglycosides to
diffuse through porin channels in their outer membranes. These
organisms also have an oxygen-dependent system that transports
the drug across the cytoplasmic membrane. The antibiotic then
binds to the 30S ribosomal subunit prior to ribosome formation.
There,
• it interferes with assembly of the functional ribosomal apparatus
and/or can cause the 30S subunit of the completed ribosome to
misread the genetic code. Polysomes become depleted, because the
aminoglycosides interrupt the process of polysome disaggregation
and assembly.

7. Mechanisms of Resistance
• enzymes inactivates the aminoglycoside by adenylylation,
acetylation, or phosphorylation
• impaired entry of aminoglycoside resulting from mutation or
deletion of a porin protein or proteins involved in transport and
maintenance of the electrochemical gradient
• The receptor protein on the 30S ribosomal subunit may be deleted or
altered as a result of a mutation.
• Clinical uses
Mycobacterial Infections, Nontuberculous Infections, Topical and
Ocular Administration, Intrathecal Administration

8. A.D.R’S
Cochlear damage, Vestibular damage, Neuromuscular blockade,
Nephrotoxicity.
Antibacterial spectrum

9. MACROLIDES
• Inhibition of protein synthesis occurs via binding to the 50S
ribosomal RNA. The binding site is near the peptidyltransferase
center, and peptide chain elongation (ie, transpeptidation) is
prevented by blocking of the polypeptide exit tunnel. As a result,
peptidyl-tRNA is dissociated from the ribosome.
• Clinical Uses
• As an alternative to penicillin, As a first choice drug for
(Mycoplasma pneumonia, Whooping cough, Syphilis and gonorrhea,
Diphtheria, Tetanus,

10. Antibacterial Spectrum
• The macrolides are effective against a number of
organisms,including Mycoplasma spp., H. influenzae, Streptococcus
spp. (including S. pyogenes and S. pneumoniae), staphylococci,
gonococci, Legionella pneumophila, and other Legionella spp.
Resistance
• 1) the inability of the organism to take up the antibiotic or the
presence of an efflux pump, both of which limit the amount of
intracellular drug;
• 2) a decreased affinity of the 50S ribosomal subunit for the
antibiotic, resulting from the methylation of an adenine in the 23S
bacterial ribosomal RNA; and
• 3) the presence of a plasmid-associated erythromycin esterase.

11. A.D.R’S
• Gastrointestinal intolerance, direct stimulation of gut motility,
acute cholestatic hepatitis, fever, jaundice, impaired liver function,
LINCOSAMIDE ANTIBIOTICS
• CLINDAMYCIN
• inhibits protein synthesis by interfering with the formation of
initiation complexes and with aminoacyl translocation reactions.
The binding site for clindamycin on the 50S subunit of the bacterial
ribosome

12. Clinical Uses
• Clindamycin is indicated for the treatment of skin and soft-tissue
infections caused by streptococci and staphylococci. It is often active
against community-acquired strains of methicillin-resistant S
aureus , an increasingly common cause of skin and soft tissue
infections.
• used to treat penetrating wounds of the abdomen and the gut;
infections originating in the female genital tract, eg, septic abortion,
pelvic abscesses, or pelvic inflammatory disease; and lung
abscesses.

13. Resistance
• (1) mutation of the ribosomal receptor site;
• (2) modification of the receptor by a constitutively expressed
methylase (see section on erythromycin resistance, above);
(3) enzymatic inactivation of clindamycin. Gram-negative aerobic
species are intrinsically resistant because of poor permeability of the
outer membrane.
A.D.R.’s
• rashes, urticaria, abdominal pain, abdominal, pelvic and lung
abscesses.

14. Chloramphenicol
• Chloramphenicol is a bacteriostatic, bactericidal broad-spectrum
antibiotic that is active against both aerobic and anaerobic gram-
positive and gram-negative organisms.
M.O.A
binds reversibly to the 50S subunit of the bacterial ribosome and
inhibits peptide bond formation.
Clinical Uses
• serious rickettsial infections such as typhus and Rocky Mountain
spotted fever, in the treatment of eye infections.

15. • Antmicrobial Spectrum
• H. influenzae , N. meningitides gram-positive and negative cocci
and bacilli, rickettsiae, mycoplasma, Salmonella including S. typhi.
Resistance
• Resistance is conferred by the presence of an R factor that codes for
an acetyl coenzyme A transferase. This enzyme inactivates
chloramphenicol.
• A.D.R’S
Gray baby syndrome, Anemias, gastrointestinal upsets, overgrowth
of Candida albicans

16. Streptogramins (Quinupristin-dalfopristin 30:70 ratio)
• Bactericidal for most susceptible organisms except Enterococcus
faecium , which is killed slowly.
• Clinical Uses
• Infections caused by staphylococci or by vancomycin-resistant
strains of E faecium , but not E faecalis .
Resistence
efflux-type resistance
A.D.R.’S
• infusion-related events, such as pain at the infusion site, and an
arthralgia-myalgia syndrome.