Chapter 37 Aminoglycosides. History 1944 StreptomycinStreptomycin 1957 kanamycin 1964 gentamicin 1967 tobramycin Amikacin & netilmicin.

Chapter 37 Aminoglycosi

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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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