Exam 8: Aminoglycosides Flashcards
Name 4 Aminoglycosides
Which is used least commonly?
Gentamicin
Tobramycin
Amikacin
Streptomycin (least commonly used)
When would you administer an aminoglycoside orally? Why?
GI indication
It is very poorly absorbed through he GI tract
How are aminoglycosides usually administered?
IV (mostly) or IM
How often are aminoglycosides usually administered? Which is now preferred?
2-3x per day
New, once daily regimens may be preferred
** He mentioned multiple times that the 2-3x/day regimen is more likely to cause toxicity
Why is once-daily admin advantageous with aminoglycosides?
Super high plasma concentrations kill more bugs (dose-dependent killing)
Less TIME with concentrations above the “Toxic Trough” (less likely to cause adverse effects)
How do aminoglycosides distribute in the body?
Not very well (polar compounds)
Dont enter CNS
Can be administered intrathecally (better options though usually like 3rd gen cephalosporins)
How do aminoglycosides enter bacterial cells?
Diffuse through porin channels in the outer membrane in gram negatives
Cross plasma membrane via an oxygen-dependent active transport process (not good with anaerobic infections!)
What can enhance transport of aminoglycosides into bacterial cells?
Antibiotics that inhibit bacterial cell wall synthesis (beta lactams)
What antibiotics have a synergistic killing effect with aminoglycosides?
Beta lactams
They allow more aminoglycoside penetration into bacterial cells.
Where do high concentrations of aminoglycosides accumulate?
Renal cortex
Inner Ear
This is why they can cause nephrotoxicity and ototoxicity
How are aminoglycosides eliminated?
By the kidneys
Adjust dose in renal failure, otherwise you’ll get really high concentrations/toxicity
What are 3 mechanisms of aminoglycosides?
- Irreversible binding to the 30S ribosomal subunit inhibits bacterial protein synthesis (translation)
- Causes breakup of 70S subunit into 30S and 50S
- Cause misreading of mRNA leading to mutated proteins (this accounts for killing effect even at concentrations below M.I.C.)
What stage of protein synthesis do aminoglycosides inhibit?
Initiation
What are 3 adverse effects associated with aminoglycosides?
- Ototoxicity
- Nephrotoxicity
- Neuromuscular block (Curare like effect)
How do aminoglycosides cause ototoxicity?
Accumulation in perilymph and endolymph of inner ear
Causes irreversible destruction of vestibular and cochlear sensory cells
What increases the risk of aminoglycoside causes ototoxicity? (3 things)
- Co-administration of ethacrynic acid, vancomycin, or cisplatin
- Renal failure
- High doses
What are two manifestations of ototoxicity?
Auditory problems
Vestibular problems
What kind of nephrotoxicity is caused by aminoglycosides?
Acute Tubular Necrosis in the proximal tubule
Monitor creatinine
What is different between the ototoxicity and the nephrotoxicity caused by aminoglycosides?
The nephrotoxicity may be reversible
The ototoxicity is irreversible
How can aminoglycosides cause neuromuscular block? (2 ways)
Inhibit ACh release
Inhibit postsynaptic sensitivity to ACh
How do you treat aminoglycoside induced NM blockade?
IV Calcium and an Acetylcholinesterase inhibitor
How can you treat the patient if you end up with toxic levels of aminoglycosides?
Hemodialysis
What should you be doing if you have a patient on aminoglycosides?
Monitoring blood levels
Make sure that you’re achieving therapeutic levels and that you’re not having concentrations too high.
What is an important resistance mechanism to aminoglycosides?
Production of bacterial enzymes that phosphorylate, adenylate, or acetylate the aminoglycoside so it can’t bind to the 30S subunit.
Genes are usually on plasmids, which often contain other resistance genes
What is the most resistant aminoglycoside to inactivating enzymes?
Amikacin
What is a resistance mechanism specific to streptomycin?
Mutated 30S subunit
How could you use aminoglycosides to treat Enterococci?
Gentamicin or streptomycin PLUS a beta lactam
What are aminoglycosides really good at treating?
Aerobic gram negatives
Proteus, E. coli, Klebsiella
What are the major uses of Aminoglycosides?
Severe systemic infections caused by gram negatives
In combo with beta lactams to treat endocarditis
Streptomycin
Used in combo with Penicillin G to treat bacterial endocarditis
Can treat gentamicin-resistant enterococci
TB
Gentamicin Uses
Hospital acquired UTI (gram neg)
Hospital acquired pneumonia in combo with an antipseudomonal (gram neg rods)
NOT good at CAP (Strep. pneumo.)
Enterococcal endocarditis (with penicillin G)
Sepsis caused by gram negatives
Tobramycin Uses
Better activity against Pseudomonas (sepsis, osteomyelitis, pneumonia)
Can be inhaled in patients with CF and pseudomonas infections
Amikacin
Broadest spectrum aminoglycoside
Resistant to inactivating enzymes
reserved for serious infections caused by gram negatives that don’t respond to the aminoglycosides
