Aminoglycosides Flashcards
What is the mechanism of action for aminoglycosides?
- Aminoglycoside binds to outer membrane of cell, resulting in a rearrangement of LPS.
- Uptake is energy dependent (slow phase and rapid phase); the source of energy is an electrochemical gradient (this gradient is decreased in an anaerobic environment).
- Once across the membrane the drug is irreversibly trapped into bacteria cytoplasm (very high intracellular concentrations).
- Aminoglycoside then binds to 30 S and 50 S ribosomal subunit, resulting in decreased protein synthesis and increased misreading of mRNA.
Are Aminoglycosides Bactericidal or Bacteristatic?
Bactericidal
T/F
Aminoglycosides (along with fluoroquinolones) exhibit Postantibiotic Effect.
T/F
Aminoglycosides exhibit ”Concentration dependent killing.”
TRUE
TRUE
Why are Amikacin, Gentamycin, and Tobramycin all given IV but Neomycin can be taken PO?
Generally, Aminoglycosides very poorly absorbed from GI Tract
Why can Aminoglycosides often be used for monotherapy in the instance of UTIs?
99% of the drug unchanged by glomerular filtration
Describe aminoglycoside distribution to the lung and inflamed meninges?
40% to lung
20% to CSF (less when not inflamed; better distribution in neonates thought due to immature blood brain barrier)
Do aminoglycosides undergo hepatic or renal elimination?
Renal Excretion as active drug (good for UTIs)
Why do you need to be careful in dosing aminoglycosides in patients who are:
Elderly
Critically Ill (dehydrated or volume overload)
Renal Disease
Cachexia/Malnourished
Decreased Vd and Ke
Change in Vd
Decreased Ke; Change in Vd
Decreased Vd & creatinine production
(I say don’t memorize)
What are the common Aminoglycosides?
Tobramycin
Amikacin
Gentamycin
Neomycin
Why isn’t Amikacin used as often as Tobramycin, Gentamycin, or Neomycin?
Closest place that runs Amikacin levels is North Carolina
What adverse reactions are associated with Aminoglycoside use?
- Thrombophlebitis
- Nephrotoxicity (20% of patients!)
- Ototoxicity
- Neuromuscular Block (rare, provide 2g Ca2+ if happens)
Really high PEAKS in aminoglycoside levels cause?
Really high TROUGHS in aminoglycoside levels cause?
OTOTOXICITY
NEPHROTOXICITY
What bugs are covered by Aminoglycosides?
GRAM NEGATIVES
- Morganella
- Haemophilus
- Providencia
- Proteus Mirabilis
- PEK
- SPACE
Which aminoglycoside covers the least bugs of them all?
Which bugs doesn’t it cover
Kanamycin
Providencia
Acinetobacter
Enterobacter
How would you cover enterococcus using aminoglycosides?
must do combo therapy for synergy; common combination is Ampicillin+Gentamycin
What specific aminoglycoside would you use to treat Tuberculosis?
What specific aminoglycoside would you use to treat Brucellosis?
Streptomycin
Gentomycin
Why use Neomycin for prophylaxis in instance of colorectal surgery?
Why use Neomycin in instance of hepatic coma?
Why use Neomycin in instance of hyperlipidemia?
suppresses intestinal flora
decrease amount of ammonia forming bacteria
decrease cholesterol absorption
T/F
Large daily doses may be equally effective as smaller multiple daily dosing with lower toxicity.
T/F
Low serum concentrations allow the kidney cells to process drug and thereby reduce effects of accumulation.
What principle allows this to happen?
TRUE
TRUE
Post Antibiotic Effect
Why is the Hartford Nomogram used for amioglycosides?
How does it work?
substantial variations exist in concentrations achieved compared to predicted values
• 7mg/kg first dose (Less if CrCl is
T/F
Aminoglycosides distribute to lung last.
T/F
Prolonged exposure to Aminoglycosides is correlated with spike in nephrotoxicity occurrance.
TRUE (higher peak values needed to achieve theraputic index for pneumonias)
TRUE
Troughs should be no higher than what to best avoid Nephrotoxicity?
Less than 2 mcg/ml
