Introduction to aminoglycosides and broad spectrum antibiotics

1. Aminoglycosides
and
broad spectrum antibiotics

2. Aminoglycosides
• Systemic aminoglycosides
– Streptomycin
– Amikacin
– Gentamicin
– Sisomicin
– Kanamycin
– Netilmicin
– Tobramycin
– Paromomycin
• Topical aminoglycosides
– Neomycin
– Framycetin

3. Aminoglycosides
• MOA:
– Aminoglycosides are bactericidal antibiotics
– Transport of the aminoglycoside through the
bacterial cell wall and cytoplasmic membrane.
– Binding to ribosomes resulting in inhibition of
protein synthesis.
– Streptomycin binds to 30S ribosomes, but other
aminoglycosides bind to additional sites on 50S
subunit, as well as to 30S-50S interface.

4. Aminoglycosides
• Toxicity/ ADR:
– Ototoxicity
• Cochlear damage
• Vestibular damage
– Nephrotoxicity
• loss of urinary concentrating
• power
• low g.f.r.
• nitrogen retention
• Albuminuria
– Neuromuscular blockade

5. Aminoglycosides
• Uses:
– Gentamicin
• It is very valuable for preventing and treating
respiratory infections in critically ill patients.
• Used for the treatment of Pseudomonas, Proteus or
Klebsiella infections and subacute bacterial
endocarditis.
– Streptomycin
• Used for the treatment of tuberculosis, subacute
bacterial endocarditis, plague and tularemia.

6. Broad spectrum antibiotics
• Aminoglycosides
• Tetracyclines
• Chloramphenicol

7. Tetracyclines
• These are a class of antibiotics having a nucleus of
four cyclic rings.
• All are obtained from soil actinomycetes.
• MOA: The tetracyclines are primarily bacteriostatic;
inhibit protein synthesis by binding to 30S ribosomes
in susceptible organism.
Tetracycline Tetracycline, Doxycycline
Oxytetracycline Minocycline
Demeclocycline
Glycylcycline Tigecycline

8. Tetracyclines
• Uses:
– Tetracyclines are the first choice drugs for venereal
diseases, atypical pneumonia, cholera, brucellosis,
plague, relapsing fever and rickettsial infections.
– Tetracyclines are the second choice drugs for tetanus,
anthrax, actinomycosis and Listeria infections.
– Others: Treatment of UTIs, pneumonia, malaria, Acne
vulgaris.

9. Tetracyclines
• ADR:
– Irritative effects: epigastric pain, nausea, vomiting and
diarrhoea on oral ingestion.
– Liver damage: Tetracyclines are risky in pregnant women; can
precipitate acute hepatic necrosis which may be fatal.
– Kidney damage: It is a risk only in the presence of existing
kidney disease.
– Phototoxicity
– Teeth and bones: Tetracyclines have chelating property.
Calcium-tetracycline chelate gets deposited in developing
teeth and bone.
– Antianabolic effect
– Increased intracranial pressure
– Diabetes insipidus
– Vestibular toxicity

10. Tetracyclines
• Tigecycline
– It is a new class of synthetic tetracycline
analogues (glycyl-cyclines) which are active
against most bacteria that have developed
resistance to the classical tetracyclines.

11. Chloramphenicol
• MOA:
– Chloramphenicol inhibits bacterial protein synthesis by
interfering with ‘transfer’ of the elongating peptide chain
to the newly attached aminoacyl-tRNA at the ribosome-
mRNA complex. It specifically attaches to the 50S
ribosome.
– Chloramphenicol is primarily bacteriostatic, though high
concentrations have been shown to exert cidal effect.

12. Chloramphenicol
• MOA:
– Chloramphenicol inhibits bacterial protein synthesis by
interfering with ‘transfer’ of the elongating peptide chain
to the newly attached aminoacyl-tRNA at the ribosome-
mRNA complex. It specifically attaches to the 50S
ribosome.
– Chloramphenicol is primarily bacteriostatic, though high
concentrations have been shown to exert cidal effect.

13. Chloramphenicol
• Uses:
• Clinical use of chloramphenicol for systemic infections is
now highly restricted due to fear of fatal toxicity. Because
of risk of serious bone marrow aplasia,
– Never use chloramphenicol for minor infections or those of
undefined etiology.
– Do not use chloramphenicol for infections treatable by
other safer antimicrobials.
– Avoid repeated courses.
• Used for the treatment of Pyogenic meningitis, anaerobic
infections, intraocular infections, enteric fever, whooping
cough, urinary tract infections and external ear infections.

14. Chloramphenicol
• ADR:
– Bone marrow depression: chloramphenicol is the most
important cause of aplastic anaemia, agranulocytosis,
thrombocytopenia or pancytopenia.
– Hypersensitivity reactions Rashes, fever, atrophic glossitis,
angioedema are infrequent.
– Irritative effects Nausea, vomiting, diarrhoea, pain on
injection.
– Gray baby syndrome:
• It occurs because of inability of the newborn to adequately
metabolize and excrete chloramphenicol.
• At higher concentration, chloramphenicol blocks electron
transport in the liver, myocardium and skeletal muscle.
• Chloramphenicol should be avoided in neonates, and even if given,
dose should be ~ 25 mg/kg/day.

15. Thank you