Aminoglycosides Flashcards
what are aminoglycosides?
highly water soluble agents - very limited ability to cross the lipid bilayers.
include antibacterial agents (but will focus on others)
what is Gentamicin
aminoglycoside
- boras spectrum of action
generally uesd to treat grma negative bacteria, gram pos staphylococci and gram positive myoplasma
what is tobramycin
clincially interchangable with gentamicin
- mainly used topically to treat bacteria that are resistant to gentamicin
- more expensive tho
what is Amikacin
resistant to most aminoglycoside-modifying enzymes
used systemicaly to treat bacteria that are resistant to gentamicin
describe bacteria protein synthesis
- protein synthesis follows transcription which involves the synthesis of single-stranded RNA transcripts from a DNA template
- ocne mRNA transcripts are synthesized they are translated
- bacterial ribosome is different bc ahs a 30S subunit and a 50S subunit
describe the MOA of aminoglycosides
- irreversibly bind to bacterial ribsomes to inhibit protein synthessi
- aminoglycosides, spectinomycin and tetracyclins all bind and iinhibit the activvity of 16S rRNA in the 30S subunit
*primarily bactericidal, blocking 30S subunit bloks protein syn, movement of ribosome and causes misreading of mRNA leading to miscoded petide chain
what antibiotics bind and inhibit the 50S subunit
acrolides, chloramphenicol, lincosamides, streptogramins, oxazolidinones, and pleuromutilins
what are the two types of resistance
constituative and plasmid-acquired
describe constituative resistance
- bc anaerobes lack the oxygen dependent transport processes that are necessary for aminoglycosides to enter the cell
describe plasmid acquired resistnace
involves the production of aminoglycoside modifying enzymes coded by several genes which modify the inactvate the drug
what drugs work synergistically with aminoglycosides?
drugs that interfere with the cell wall - beta lactams (damage anaerobe cell walls so can combine with aminoglycosides to let them enter the cell)
what are the main uses of aminoglycosides
only two main suses
- treat severe syntemic gram negative aerobic infections
- topical treatment to treat staphylococci infections
- limited ability to cross membranes
*if given orally the abs is very low (~3%) so must be given parenterally for systemic treatment
side effects of aminoglycosides
- nephrotoxicity:
- enhance the free radical formation following accumulation in renal tubular cells, even an ordinary dose can be damaging to kidneys of dehydrated aptients or those with renal disease
- half life usually doubles in elderly patients, excretion is directly proportional to creatinine clearance
ototoxicity
- toxicity of ear
- damage to cranail nerves and fair cellsin the cochlea and vestibular apparatus which can cause permanent, severe, high frequqncy hearing loss and temporary vestibular impairment
- hearing loss accompanies by degeneration of the hair cells and the neurons in the cochlea
- Some develop hearing loss after one day of treatment others no hearing loss even after several months of treatment.
- that susceptible individuals metabolize aminoglycosides to a cytotoxin, and this ability appears to be inherited.
how can you minimize the nephrotoxicity damage of aminoglycosides
- allow a washout period each day
- single daily dose and allowing the conc to fall for remainder of day
relationship between aminoglycoside chelation and ototoxicity
an iron aminoglycoside complex is believed to potentiate free radical induced cellular degeneration in the chochlea
-chelation of calcium may better explain the pattern of cochlear hair cell damage where high-frequency cells are lost first and then it progresses to lower frequency cells, in a calcium-sensitive manner.
