Aminoglycosides Flashcards
What is the mechanism of action of aminoglycosides
- inhibit protein biosynthesis by binding to the 30S ribosomal subunit
- bind to 16S rRNA forming the A site, which interferes with the formation of the initiation complex
- also forms nonsense proteins via frameshift at the 30S ribosomal subunit
- lead to leakage of ions and disruption of the cytoplasmic membrane resulting in cell death
What is the bacterial uptake of aminoglycoside mechanism
initial entry of positively charged aminoglycosides through the outer membrane involves the displacement of magnesium and calcium ions that form salt bridges with phosphate of the phospholipids in the membrane, making the membrane more permeable to the aminoglycosides (active transport)
What are the three bacterial resistance mechanisms
- bacteria inactivate aminoglycosides by acetylation, adenylation, and phosphoylation
- altered ribosome at the 16S rRNA binding site through point mutations (mycobacterium tuberculosis)
- altered aminoglycoside uptake
Common toxicities of aminoglycosides
- irreversible ototoxicity
- reversible nephrotoxicity (monitor CrCl)
- curare like effects
- respiratory paralysis
What are the symptoms of aminoglycoside otoxicity
- tinnitus
- high frequency hearing loss
- vertigo
- loss of balance
- ataxia
- roaring in ears
Which aminoglycoside toxicities are irreversible
ototoxicity
what aminoglycoside toxicities are reversable
nephrotoxicity
Which drugs can potentiate the nephrotoxicity of the aminoglycosides
- ethacrynic acid
- furosamide
- vancomycin
- amphotericin
Toxic effects of aminoglycosides can have on respiration and how it can be reversed or treated
- respiratory paralysis can be reversed by neostigmine or calcium gluconate (calcium increases depolarization at junction caused by acetylcholine
- mechanical respiratory assistance may be necessary
What are the risk factors for manifestation of aminoglycoside toxicity
- increases with treatment period of 5 days
- in the elderly
- if renal function is impaired
- higher dose
How can aminoglycoside toxicity can be minimized
- more effective and less toxic alternatives to aminoglycosides are usually available
- only used sparingly and only for specific indications
What are the main clinical uses of aminoglycosides
broad spectrum, but almost always reserved for the treatment of gram negative bacteria
Should aminoglycosides and penicillins be administered together in the same solution/injection site?
NO, they will inactivate each other
What is the aminoglycoside induced frame shift
- causes the 30S ribosomal subunit to cause a frame shift
- in stead of a codon CCG, a codon CGU is read
- results in formation of altered proteins
What is amikacin used for
- myobacterium tuberculosis
- francisella tularensis
- severe pseudomonas aeruginosa resistant to otehr agents
- aminoglycoside-resistant nosocomial infections in hospitals
