antibiotics that inhibit synthesis of the bacterial cell wall. includes tetracyclines, aminoglycosides, macrolides and ketolides , chloramphenicol among others. this presentation highlights the clinical uses, adverse effects, common contraindications modes of action and susceptibility scores

1. PROTEIN SYNTHESIS INHIBITORS
MUDOOGO EDGAR
PRESENTATION TO MBCHB3 CLASS BUSITEMA UNIVERSITY

2. PREAMBLE
 Exert their antimicrobial effects by targeting bacterial ribosomes
and inhibiting bacterial protein synthesis.
 Utilize the difference in the ribosomes.
 selectivity for bacterial ribosomes minimizes potential adverse
consequences encountered with the disruption of protein synthesis
in mammalian host cells
 High doses of chloramphenicol and tetracyclines interact with
mitochondrial ribosomes

5. TETRACYCLINES
Mode of action
 bacteriostatic
 enter susceptible organisms via
 passive diffusion and
 energy-dependent transport protein mechanism
 bind reversibly to the 30S subunit of the
bacterial ribosome.
 Prevents binding of tRNA to the mRNA–
ribosome complex
 Chlamydia is susceptible to doxycycline

6.  Resistance develops due to:
 Efflux pumps
 enzymatic inactivation of the drug
 production of bacterial proteins that prevent tetracyclines from
binding to the ribosome.

7. Pharmacokinetics
 adequately absorbed after oral ingestion
 Administration with dairy products or other substances that contain
divalent and trivalent cations (magnesium & aluminum antacids or iron
supplements) decreases absorption, due to the formation of non-
absorbable chelates
 doxycycline and minocycline are available as oral and IV preparations.
 concentrate well in the bile, liver, kidney, gingival fluid, and skin.
 they bind to tissues undergoing calcification (teeth and bones) or to
tumors that have a high calcium content.
 Only minocycline and doxycycline achieve therapeutic levels in the
cerebrospinal fluid (CSF).
 cross the placental barrier and concentrate in fetal bones and teeth.

8.  Elimination:. Tetracycline is primarily eliminated unchanged in
the urine, whereas minocycline hepatic metabolism & kidney,
doxycycline via bile.
 Adverse effects: GI discomfort, phototoxicity, hepatotoxicity,
vestibular dysfunction, psedotumor celebri, effects on
tissues
 Contraindications: pregnant ,breast-feeding women, in
children less than 8 years of age.

9. AMINOGLYCOSIDES
 Derive their name from two amino sugars joined by a glycosidic linkage to a
central hexose nucleus.
 Produced naturally by Streptomyces sp. or Micromonospora sp.
 Bind to 30S ribosomal subunit causing misreading of the genetic code
 Bactericidal and concentration dependent
 Have PAE(post antibiotic effect)
 Effective against majority of aerobic gram negative bacilli,
 Combined with a β-lactam antibiotic to employ a synergistic effect, in rx of E.
faecalis and E. faecium infective endocarditis
 resistance mechanisms are aminoglycoside specific

10.  Polycationic, prevents adequate absorption after oral administration.
 Neomycin is not given parenterally due to severe nephrotoxicity, administered
topically for skin infections
 Concentrations in CSF are inadequate, even in the presence of inflamed
meninges ,IT route may be utilized
 All aminoglycosides cross the placental barrier and may accumulate in fetal
plasma and amniotic fluid.
 More than 90% of the parenteral aminoglycosides are excreted unchanged in
urine
 Adverse effects: ototoxicity,nephrotoxicity,neuromuscular paralysis,allergic
reaction

11. MACROLIDES AND KETOLIDES
 bind irreversibly to a site on the 50S subunit of the bacterial ribosome, inhibiting
translocation steps of protein synthesis ,may also transpeptidation.
 bacteriostatic, may be bactericidal at higher doses.
 Erythromycin: effective against many of the same organisms including penicillin allergy.
 Clarithromycin: also effective against Haemophilus influenzae., Chlamydia, Legionella,
Moraxella, Ureaplasma species and Helicobacter pylori.
 Azithromycin: respiratory infections due to H. influenzae and Moraxella catarrhalis.
 . Telithromycin: This drug has an antimicrobial spectrum similar to that of azithromycin
 Resistance:Reduced penetration, efflux pumps, decreased affinity of the 50S ribosomal
subunit for the antibiotic, erythromycin esterases

12.  All are adequately absorbed upon oral administration, food interferes with the
absorption of erythromycin and azithromycin.
 Erythromycin distributes well to all body fluids except the CSF.
 Erythromycin and azithromycin -bile as active drugs, clarithromycin -kidney &
liver.
 Adverse effects: GI motility, cholestatic jaundice, ototoxicity
 Contraindications: hepatic dysfunction, proarrythmic patients

13. CHLORAMPHENICOL
Mode of action
 binds reversibly to the bacterial 50S ribosomal subunit inhibiting peptidyl
transferase reaction
Antibacterial spectrum
 chlamydiae, rickettsiae, spirochetes, and anaerobes primarily
bacteriostatic, but depending on the dose and organism, it may be
bactericidal.
 Resistance is by the presence of enzymes that inactivate chloramphenicol.
,poor penetration and ribosomal binding site alterations.

14. Pharmacokinetics
 Chloramphenicol is administered intravenously and is widely distributed
throughout the body
 Chloramphenicol primarily undergoes glucuronidation, and eliminated in
urine.
 Dose reductions are necessary in liver dysfunction/ cirrhosis.
 It is also secreted into breast milk and should be avoided in breastfeeding
mothers.
 Adverse effects: anemia(hemolytic in G6PDH, aplastic), gray baby syndrome,
Drug interactions: inhibits some of the hepatic mixed-function oxidases ,blocks
the metabolism of warfarin and phenytoin, increasing their concentrations.

15. CLINDAMYCIN
 mechanism of action & resistance mechanisms that is the same as that of erythromycin.
 Clindamycin is used primarily in the treatment of gram-positive organisms are the same
as those for erythromycin,
 IV and oral formulations, but oral form is limited by GI problems.
 exhibits poor entry into the CSF.
 Clindamycin undergoes extensive oxidative metabolism to inactive products and is
primarily excreted into the bile.
 Accumulation has been reported in patients with either severe renal impairment or
hepatic failure.
 Skin rashes, diarrhea (C. difficile).
 Oral administration of either metronidazole or vancomycin is usually effective in the
treatment of C. difficile.

16. READ UP……………….
 Oxazolidinones
 Lincosamides
 Macrocyclic antibiotics

17. REFERENCES

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