Aminoglycosides

2. Introduction
• Bactericidal Protein synthesis inhibiting drug mainly (Gram-negative aerobes)
• History:-
• Two amino sugar joined to a non-sugar moiety by glycosidic bond (-O-)
• Drugs-Streptomycin, Gentamicin, Tobramycin, Amikacin, Kanamycin,
Sisomicin, Neomycin (T), Framycetin (T) and Netilmicin, Paromomycin

3. -:Common properties of aminoglycosides:-
1. They are highly polar compounds, hence, poorly absorbed from the GI tract.
2. Effective mainly against:-Aerobics Gm-Negative (bacilli)
3. Administered-Parenteral route (i.m. /i.v.) for systemic effect.
4. Poor penetrate into the CSF & BBB
5. Not metabolized in body so excreted unchanged in urine
6. Exhibit Ototoxicity and Nephrotoxicity
7. Exhibit partial cross-resistance among them.
8. Transport of aminoglycosides across cytoplasmic membrane requires oxygen &
energy hence “anaerobes are resistant to aminoglycosides”

4. • MOA:-
They process concentration dependent killing i.e.higher conc. Kills more bacteria at rapid rate
Also process Post Antibiotic effect

5.  Development of Resistance by-
• inactivation of the drug by bacterial enzymes
• ↓ entry of drug into bacterial cell
• ↓ affinity of the drug for the ribosomes
 Antibacterial spectrum:-
 gram- ve aerobic bacilli except salmonella
 Gram+ ve cocci e.g.-S aureus & streptococcus viridians
 Not effective against anaerobes
 Pharmacokinetics:-
 Absorption-Highly polar not absorbed orally (parental use i.m.
/i.v.)
 Distribution- poor penetration to CSF & Intraocular fluid
 Metabolism- not in body
 Excretion-kidney (high conc. In urine so useful in UTI & dose
reduction needed in renal failure)

6. • Therapeutic uses:-
1. Dental uses:- (not commonly use)
• Prophylaxis of bacterial endocarditis- combination with penicillin(amoxicillin)
(Penicillin G+ gentamicin)
• Prosthetic heart valves
Side effect:-
• Ototoxicity:- more likely due to prolonged use,toxicity ,renal failure

7. • Vestibular and cochlear dysfunctions can occur due to VIII- cranial nerve damage
• They get concentrated in the perilymph and endolymph of the inner ear
• Nephrotoxicity:- reversible
• Highest→ neomycin(not indicated for systemic use)
• least →streptomycin
• Risk factor- Hypokalemia, Renal disease, concomitant nephrotoxic drugs-e.g.-
Amphotericin-B, Vancomycin, ACE-I, Cisplatin, cyclosporine
• NM-blocked-Apnoea and muscular paralysis
Cochleotoxic
Vestibulotoxic
Amikacin, kanamycin, Neomycin
(Hearing loss)
All other aminoglycosides (maximum by
streptomycin & Gentamicin)

8. • Myasthenic patients are more susceptible to neuromuscular blocking effect of
these drugs, hence should be avoided
• Hypersensitivity reactions:- are rare; occasionally skin rashes, drug fever and
eosinophilia can occur.
• Cross sensitivity between aminoglycosides may occur.
• Use of aminoglycosides during pregnancy may cause ototoxicity in the foetus
• Streptomycin:-
• Streptomycin was the first aminoglycoside discovered in 1944.
• Uses:- first-line drugs for TB and is used in combination with other
antitubercular drugs.
• Tularaemia, plague and brucellosis.

9. • Gentamicin:-most commonly used aminoglycoside antibiotic for aerobic gram-
negative bacillary infections
• It is also effective against gram-positive
• Infections—enterococci, S. viridans and staphylococci but not M. tuberculosis.
• Neomycin:-highly nephrotoxic(No systemic use)
• Used topically in combination with bacitracin or polymyxin B for wounds, ulcers,
burns, and infections of eye and ear.
• Amikacin:-broadest spectrum aminoglycoside.
• It is useful for the treatment of nosocomial gram-negative infections and TB
(Anti-TB drugs)