1. Chapter 37 Aminoglycosides

2. History 1944 Streptomycin 1957 kanamycin 1964 gentamicin
1967 tobramycin
Amikacin & netilmicin

3. General properties of Aminoglycosides

4. Phsical and chemical properties
Structure
Water-soluble, stable in solution
More active at alkaline than at acid pH

5. 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

6. 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

7. 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

8. 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

9. Clinical uses Infections caused by sensitive G- rods
Topical infections
Tuberculosis
Infections caused by P. aeruginosa

10. 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

11. Adverse reactions Ototoxicity Nephrotoxicity Neuromuscular blockade
Auditory damage:tinnitus, hearing loss
Vestibular damage:vertigo, ataxia and loss of balance
Nephrotoxicity
Neuromuscular blockade
neostigmine and calcium gluconate
Allergic reactions

12. The commonly used aminoglycosides

13. Streptomycin Clinical uses Tuberculosis first line
Plague, tularemia and brucellosis:
combination with tetracycline
Enterococcal and viridans streptococcal
endocarditis: combination with penicillin G

14. Gentamicin Clinical uses
Severe infections caused by gram-negative 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

15. Kanamycin Topical administration
Oral administration in preparation for elective bowel surgery

16. Tobramycin Similar antibacterial spectrum with gentamicin
More active against P.aeruginosa
Treat infections caused by P.aeruginosa
that are resistant to gentamicin

17. Amikacin The most wide antibacterial spectrum
Resistant to many enzyme that inactivate gentamicin and tobramycin

18. Netilmicin
Resistant to many enzyme that inactivate gentamicin and tobramycin
Lowest toxicity among aminoglycosides