Aminoglycosides

They are bactericidal antibiotics.

They have concentration dependent killing mechanism.
They have post antibiotic effect.
They are active against Gram ve aerobic organisms.
They are poorly absorbed orally.
They are given intramuscularly, intravenously, or intrathecally.
They do NOT freely cross the blood brain barrier.
They are excreted mainly unchanged in urine via glomelular filtration.Excretion is directly
propotional to creatinine clearance.
Half life : 2-3 h
They are more active in alkaline media.
MOA : They penetrate the cell envelope depending upon oxygen depending active transport.
Activity is increased by using cell wall synthesis inhibitors. They inhibit protein synthesis by
binding to 30S ribosomal subunits and causes three effects.
i- Block formation of initiation complex
ii- Misreading of the code on mRNA template
iii- Inhibit Translocation


MECHANISM OF RESISTANCE :

a) Faliure of drugs to penetrate the cells ( Strep cooci and enterococci Gentamicin)
b) Plasma mediated formation of inactivating enzymes (Group transferases) : catalyze the
acetylation of amine functions and transfer of hydroxyl group on the aminoglycoside
This takes place in gram ve bacteria
c) Transferases can inactive amikacin, gentamicin and tobramycin
Streptomycin can not be inhibited.




Clinical Uses :
- Gentamcin, tobramycin and amikacin Infections cause by E-colim Enterobacter ,
Klebsiella, Proteus , Providencia, Pseudomonas and Serratia, Strains of H- Influenzaie ,
Moraxella, catarrhalis and Shigella.
- Streptomycin ( in combination with penicillin)
Enterococcal carditis, TB, Plague, Tularemia
- Amikacin M.Tuberculosis
- Neomycin & Kanamycin Topical and Oral use (to eliminate
bowel flora); not used otherwise due to toxicity.
- Gentamicin-topical
- Netilmicin Not longer used. Was used as substitute to
other aminoglycosides
- Spectinomycin Aminocyclitol , used as backdrug, IM
used, Single dose for treatment of Gonorrhea ( B-lactam sensitive
patients), may cause pain at injection site. No cross resistance.

Adverse effects
(1) Aminoglycosides have a narrow therapeutic index; it may be
necessary to monitor serum concentrations and individualize the
dose.
(2)OTOTOXIC : Aminoglycosides are ototoxic, affecting either
vestibular (streptomycin, gentamicin, and tobramycin) or cochlear
auditory (neomycin, kanamycin, amikacin [Amikin], gentamicin,
and tobramycin) function.
(3)NEPHROTOXIC :Aminoglycosides are nephrotoxic; they
produce acute tubular necrosis that leads to a Reduction in the
glomerular filtration rate and a rise in serum creatinine and blood
urea nitrogen. Damage is usually reversible.
(4)NM Blockade: At high doses, these agents produce a curare-like
neuromuscular blockade with respiratory paralysis. Antidote :
Calcium gluconate and neostigmine are antidotes.
(5)SKIN REACTIONS : Aminoglycosides rarely cause
hypersensitivity reactions, except spectinomycin and
neomycin,which, when applied topically, can cause contact
dermatitis in as many as 8% of patients