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Chapter 37 Aminoglycosi
des
History1944 Streptomycin1957 kanamycin1964 gentamicin1967 tobramycinAmikacin & netilmicin
General properties of Aminoglycosides
Phsical and chemical properties
StructureWater-soluble, stable in solutionMore 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 pep
tide formation induce misreading of mRNA,resulting in nonf
unctional 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, ivDistribution :
low concentration in most tissue except renal cortex
Can pass placental barrier, ×BBBExcretion: in unchanged form by glo
merular 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 othe
r 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 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
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 ge
ntamicin and tobramycin
Lowest toxicity among aminoglycosides
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