19. Aminoglycosides Flashcards
What are aminoglycosides drugs obligatory to know?
- streptomycin
- neomycin
- gentamycin
- tobramycin
- amikacin
- spectinomycin
Structure of aminoglycosides
- lots of amino groups (more amino groups, more toxicity)
- glycoside binding (exc. spectinomycin)
spectinomycin technically doesn’t belong to AG structurally (aminocyclitol)
Mechanism of action of AGs
- Targets 30S subunit
- false, non-functional proteins will be produced
- oxygen is required (doesn’t work against anaerobic bacteria)
also other mechanisms: cell membrane toxicity and RNA-structure damage
Mode of action of AGs:
bactericidal (exc. spectinomycin)
concentration dependent
+ PAE (4-8h)
Antibacterial spectrum of AGs:
- gram– aerobic + Staphylococcus spp.
- Mycobacterium (streptomycin)
- Mycoplasma (spectinomycin)
- Pseudomonas aeruginosa (genta, tobra, amikacin)
Resistance against AGs:
- ab ovo (anaerobic)
- altering enzymes (acetylation, adenylation)
- reduced cell wall permeability
- cross resistance (strepto ‹ neo ‹ genta ‹ tobra, amikacin)
Plasmids encoded
Pharmakokinetics of aminoglycosides
Hydrophilic
Absorption: po ‹-› parental
Distribution: accumulation
Metabolism: no significant metabolism (hydrophilic), can be given even to liver impairment patients
Elimination: kidney (active form)
Toxicity of AGs:
One of the most toxic AB group
- ototoxic
- nephrotoxic
- inhibition of ACh release
- Absorption and accumulation in the cells (membrane damage)
- Pinocytosis in the cell (lysosomal destruction, damage of mitochondria)
Neomycin - most toxic of all
Spectinomycin - least toxic of all
Neo › genta › strepto › amikacin › spectinomycin
Contraindications for AGs:
- kidney patients (nephrotoxicity)
- NOT in dehydrated animals
- NEVER with myorelaxants or in myasthenia gravis (ACh)
Indications for AGs:
- respiratory infections
- GIT infections
- UTI
- Mastitis
- Dermatitis
- Topical administration
- Septicaemia (combination)
- Leishmaniosis (paromomycin)
Streptomycin
not alone, usually with penicillins
Neomycin
- alone
- combination with penicillins
- GIT (E. coli), mastitis
Framycetin
neomycin B
component of neomycin
- ear and eye infections (acterial blepharitis, bacterial conjunctivitis, corneal injuries, corneal ulcers)
- subclinical mastitis intramammary infusion (DC) (+ penethamate hydriodide, + benethamine penicillin)
Gentamycin
- alone
- combination with beta-lactam
- GIT infection (E. coli), mastitis
- Pseudomonas aeruginosa
Netilmycin
- similar to gentamycin, but less ear and kidney toxicity
- septicaemia
- skin infections
- intra-abdominal infections
- lower respiratory tract infection
Ususally is used in combination with beta-lactam
Is active against a number of gentamycin-resistant Gram– bacteria and against Pseudomonas
