Amimoglycoside Antibiotics Flashcards
How do aminoglycosides inhibit protein biosynthesis?
by binding to the 30S ribosomal subunit - they bind to the 16S rRNA forming the A site
What happens when aminoglycosides bind to the 16S rRNA (forming the A site)?
This interferes with formation of the initiation complex, blocks further translation, and elicits premature termination
What happens when aminoglycosides impair the proofreading function of the ribosome?
formation of “nonsense proteins” resulting from selection of the wrong amino acids during translation
What do “nonsense proteins” do to the bacteria?
impair bacterial cell wall function
significance of damaged bacterial membranes?
damaged membranes have altered permeability characteristics and actually allow transport of larger amounts of aminoglycoside, and protein synthesis ceases altogether
What do aminoglycosides ultimately lead to?
leakage of ions and disruption of the cytoplasmic membrane, resulting in cell death
Describe the metabolism mechanism of aminoglycoside bacterial resistance.
bacteria inactivate aminoglycosides by acetylation, adenylation, and phosphorylation
Resistance can emerge to aminoglycosides in general because many of the metabolizing enzymes have?
cross-resistance specificity
Describe the mechanism of aminoglycoside resistance where the ribosomes are altered.
The 16S rRNA binding site can be altered through point mutations
Toxicity of aminoglycosides.
ototoxic (irreversible) and nephrotoxic (reversible)
What are the symptoms of aminoglycoside ototoxicity?
irreversible tinnitus and high-frequency hearing loss, or in vestibular damage resulting in vertigo, loss of balance and ataxia
What should you do in high risk patients if you are concerned about ototoxicity?
obtain a serial audiogram for early recognition
Risk factors for ototoxicity with aminoglycosides?
concurrent use of other ototoxic drugs (loop diuretics or vancomycin), compromised renal function or genetic vulnerability
loop diuretics
ethacrynic acid and furosamide
What can potentiate nephrotoxicity with aminoglycosides?
concurrent use with loop diuretics (ethacrynic acid and furosamide) or other nephrotoxic antimicrobial drugs (vancomycin or amphotericin)
What should be monitored in order to avoid nephrotoxicity?
creatinine clearance (changes in GFR)
Evidence of ototoxicity or nephrotoxicity with aminoglycosides requires you to?
discontinue the drug or adjust the dose
What type of effects can result from large doses of aminoglycosides?
curare-like effects (less common)
How can the respiratory paralysis (curare-like effects) from aminoglycoside toxicity be reversed?
by neostigmine or calcium gluconate (mechanical respiratory assistance may be necessary)
The likelihood of aminoglycoside toxicity increases if?
the treatment period is longer than 5 days, in the elderly if renal function is impaired and in higher doses
Since more effective and less toxic alternatives to aminoglycosides are available, they should be used…?
sparingly and only for specific indications
In practice, aminoglycosides are almost always reserved for treatment of?
gram (-) bacteria
Aminoglycosides are often used in combination with?
penicillins - synergism between the two classes of antibiotics
How should a combination of an aminoglycoside and a penicillin be administered?
should be administered in different compartments in order to avoid a chemical reaction between the two classes (penicillins and aminoglycosides attack and destroy each other)
What should you not do with aminoglycosides and penicillin?
do not mix them together in the same solution
penicillin/aminoglycoside combinations are used to treat?
bacterial endocarditis
Streptomycin is most often used to treat?
tuberculosis
Most important of the aminoglycosides
gentamicin
Gentamicin is used to treat?
urinary tract infections, burns, some pneumonias, and joint and bone infections caused by susceptible gram (-) infections
Which aminoglycoside has retained antibacterial activity against aminoglycoside-resistant strains (still used to treat nosocomial infections)?
amikacin
