7 – Aminoglycosides Flashcards
Aminoglycosides structure
- Lots of amino groups
- **basic molecules
o In more acidic pH=IONIZED
o lots of + charges=may change distribution
**What are the NEED to know aminoglycosides in Vet Med?
- Gentamicin
- Amikacin
Gentamicin examples
- Gentocin
- Otomax, Mometamaxx, Easotic
- Topagen
Gentocin
- Sterile injectable solution (clear)
- IM, SC or IU (intra-uterine in mares) on label
- *often IV off-label
Otomax, Mometamaxx, Easotic
- Topical ointments for otitis externa
- *antibiotic, steroid and anti-fungal all together
Topagen
- Topical spray for dermal lesions
Amikacin example
- Amiglyde-V
Amiglyde-V
- Sterile ‘injectable’ solution
- *labelled only for IU use in mares
- **often administered IV off label
(Neomycin)
- Used to be big in vet med
- Various calf scour boluses
- Skin and ear ointments
- Antimicrobial “preservative” in many vaccines (to ensure NO infection of the vaccine itself)
(Apramycin)
- Apralan oral solution for swine scours caused by E. coli
What is the mechanism of action of aminoglycosides?
- Binds to bacterial ribosomal 30S sub-unit
o Causes incorrect tRNA translation
o Disrupts bacterial protein synthesis
o Lead to increased bacterial membrane permeability
**Aminoglycosides need to penetrate bacterial cell to reach binding site: what is needed and what happens?
- *need oxygen for the aminoglycosides to be taken up by the bacteria (OXYGEN DEPENDENT)
- *if anaerobic environment=poor efficacy!
Local pH and aminoglycoside efficacy
- Basic pH: non-ionized, easier to transport but can diffuse out
- Acidic pH: more ionized, less transport in but, then ion-trapped
- *unsure fully
Abscess and aminoglycoside efficacy
- Does NOT work=cannot penetrate
o Anaerobic!
What are aminoglycosides generally effective against?
- *’opposite of penicillin
- **Very good against gram NEGATIVE aerobic bacteria
o Especially enteric bacteria
o *Pseudomonas - Good against Staph
o Including some MRSA/MRSP - Some activity against Enterococcus, mycobacteria and mycoplasma
What are aminoglycosides generally NOT or LESS effective against?
- Less against Strep spp..
o Especially amikacin - Intracellular pathogens
o Salmonella - *anaerobes
Aminoglycosides: main resistance mechanism
- *plasma-mediated enzymes degrade them and PREVENT BINDING to ribosome 30S subunit
o **most significant for determining clinical susceptibility
o Amikacin is LEAST affected by these enzymes
What are some other resistance mechanism against aminoglycosides?
- Decrease permeability
- Chromosomal resistance: NOT a big deal
Chromosomal resistance and aminoglycosides
- Changes to 30S binding sites
- Many 30S binding sites available, so these mutations don’t usually produce clinical resistance
“First exposure adaptive resistance” - Decreased permeability and aminoglycoside resistance
- Due to decreased uptake (permeability) by bacteria
- Occurs within 1-2h of dose
- Lasts up to 16h post-exposure
o Then partial return of susceptibility - *resistance accumulates with increasing number of doses
- IMPLICATION: use ONCE DAILY dosing with HIGH concentrations to decrease adaptive resistance effect
Order of drugs: potency, spectrum of activity, stability against enzyme degradation (MORE to LEAST)
- Amikacin: more potent spectrum against gram negative (but decrease gram positives, esp. Strep activity, DOES NOT MATTER)
- Gentamicin
- Neomycin
- Streptomycin
Oral bioavailability
- Very poor
- Historically found in calf scour boluses
- Exception: some absorbed during enteritis or with high doses
o Leave drug residues
IM/SC injection bioavailability
- Good absorption
- *due to toxicity concerns=often give IV (EXTRALABEL)
IU (label) or IMM (ELDU, cows, do NOT recommend) bioavailability
- Some systemic absorption