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Chapter 37
Aminoglycosides
History
 1944
Streptomycin
 1957 kanamycin
 1964 gentamicin
 1967 tobramycin
 Amikacin & netilmicin
General properties of
Aminoglycosides
Phsical and chemical properties
 Structure
 Water-soluble,
stable in solution
 More active at alkaline than at acid
pH
Antibacterial spectrum
High activity against aerobic G- rods
 Effective on MRSA
netilmicin
 Less active on gram-negative cocci
 P.aeruginosa: gentamicin,tobramycin,

amikacin and netimicin
Resisant to enterococci and anaerobe
 Mycobacteria: streptomycin, kanamycin

Mechanism of Action
Inhibit protein synthesis irreversibly
 interfering with the initiation complex of
peptide formation
 induce misreading of mRNA,resulting in
nonfunctional protein
 inhibit the break of 70s initiation complex
Increasing the permeability of cell membrane
Mechanism of resistance
 Produce
enzyme that inactivate the
aminoglycoside by adenylylation,
acetylation and phosphorylation
 Impared entry of aminoglycoside into
the cell
 Alteration of target protein
Pharmacokinetics
 Absorption:
po poorly, im, iv
 Distribution :
low concentration in most tissue except
renal cortex
Can pass placental barrier, ×BBB
 Excretion:
in unchanged form by
glomerular filtration
Clinical uses
Infections caused by sensitive G- rods
 Topical infections
 Tuberculosis
 Infections caused by P. aeruginosa

Adverse reactions
Dangerous factors:
Using continuously more than 5 days
 High dose
 Eldly and children
 Renal insufficiency
 Concurrent use with loop diuretics or
other nephrotoxic drugs

Adverse reactions

Ototoxicity
 Auditory damage:tinnitus, hearing loss
 Vestibular damage:vertigo, ataxia and loss of balance
Nephrotoxicity
 Neuromuscular blockade

neostigmine and calcium gluconate

Allergic reactions
The commonly used
aminoglycosides
Streptomycin
Clinical uses



Tuberculosis first line
Plague, tularemia and brucellosis:
combination with tetracycline
Enterococcal and viridans streptococcal
endocarditis: combination with penicillin G
Gentamicin
Clinical uses
 Severe infections caused by gramnegative bacteria such as pseudomonas,
enterobacter, serratia, proteus(变形杆菌）,
acinetobacter（不动杆菌） and klebsiella
 P.aeruginosa infections: combination
with carbenicillin
 Endocarditis
 Bowel preparation for elective surgery
Kanamycin

Topical administration

Oral administration in preparation for
elective bowel surgery
Tobramycin

Similar antibacterial spectrum with gentamicin

More active against P.aeruginosa

Treat infections caused by P.aeruginosa
that are resistant to gentamicin
Amikacin

The most wide antibacterial spectrum

Resistant to many enzyme that inactivate
gentamicin and tobramycin
Netilmicin

Resistant to many enzyme that inactivate
gentamicin and tobramycin

Lowest toxicity among aminoglycosides
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