Aminoglycosides Flashcards
15.23-15.25
Aminoglycosides - Name the 6
- Gentamicin
- Neomycin
- Streptomycin
- Tobramycin
- Amikacin
- Netilmicin
Aminoglycosides - MOA (3 effects)
Antimicrobial; bactericidal
Effects of aminoglycosides on protein synthesis.
- Binds to the 30S ribosomal subunit and interferes with initiation of protein synthesis by fixing the 30S-50S ribosomal complex at the start codon (AUG) of mRNA
- Binding to the 30S subunit also causes misreading of mRNA, leading to A). premature termination of translation with detachment of the ribosomal complex and incompletely synthesized protein or B). incorporation of incorrect amino acids, resulting in the production of abnormal or nonfunctional proteins.
Aminoglycosides - Tx (2)
Complicated pyelonephritis and catheter associated UTI (given IV) in combo w/ a fluoroquinolone, 3rd gen cephalosporin, or piperacillin-tazobactam
Aminoglycosides - MOR (3 enzymes)
Resistance via plasmid mediated enzymes that inactivate the drug –> acetylase, adenylase, phosphorylase
Aminoglycosides - Tox (4)
- Ototoxicity (irreversible damage to vestibular and cochlear sensory cells)
- Neuromuscular blockade (inhibits ACh release from preganglionic terminal via competition w/ Ca2+ –> antagonized by Ca2+ salts and anti-AChE)
- Nephrotoxicity (mild reversible impairment (decreased concentrating, mild proteinuria, casts) –> acute tubular necrosis –> due to accumulation of and retention of drug in PCT cells) => may prevent drug excretion and increase ototoxicity
- Teratogenic
Gentamicin ; Tobramycin; Amikacin; Netilmicin; Streptomycin; Neomycin - Class
Aminoglycosides
How do you give Gentamicin?
IV or IM (protected from 1 type of acetylase enzyme)
How do you give Tobramycin and what is it best w/?
IV, IM, or inhalation
Superior activity against P. aeruginosa in combo w/ pseudomonal beta-lactamase inhibitor
Not protected from any of the 3 MOR enzymes
How do you give Amikacin and what is it best w/?
IV or IM
Broad spectrum against gram (-) bacteria
Lowest resistance rates (because only acetylase can inactivate it at 1 site)
Netilmicin - good for
Broad spectrum against gram (-) bacteria
Protected against 1 type of acetylase enzyme and adenylase at 1 site
Streptomycin - major toxicity?
Higher ototoxicity
Neomycin - used for and major tox?
Oral, topical, and bladder irrigation
Hypersensitivity toxicity
What usually causes a urinary catheter associated UTI?
Enterobacteriaceae (gram negative bacilli)
What are the 2 major SE of Aminoglycosides?
Nephrotoxicity and ototoxicity
Why does ototoxicity develop?
Results from progressive damage to vestibular and cochlear sensory cells, which is usually irreversible
Toxicities associated with aminoglycosides are _____-dependent
dose
Why do aminoglycosides produce neuromuscular blockade?
By inhibiting acetylcholine release from the preganglionic terminal (through competition with Ca2+) and to a lesser extent by noncompetitively blocking the receptor.
How can you antagonize the neuromuscular blockade caused by aminoglycosides?
Ca2+ salts but only inconsistently by anti-cholinesterase agents
What is the other class of antibiotics that can cause neuromuscular blockade?
Tetracyclines (thought to be through chelation of Ca2+)
How many pts who receive aminoglycoside develop renal toxicity?
Up to 26% of patients (who receive an aminoglycoside for more than several days) will develop mild, reversible renal impairment.
How does renal toxicity develop from aminoglycosides?
From accumulation and retention of aminoglycoside in the proximal tubular cells.
How does renal toxicity from aminoglycosides present initially? (3)
Defect in renal concentrating ability, mild proteinuria, and the appearance of hyaline and granular casts.
With prolonged use of aminoglycosides how does the renal toxicity change? (2)
- The GFR is reduced after several additional days. 2. The nonoliguric phase of renal insufficiency is thought to be due to the effects of aminoglycosides on the distal portion of the nephron with a reduced sensitivity of the collecting-duct epithelium to endogenous antidiuretic hormone.
Does acute tubular necrosis (ATN) happen with aminoglycosides’ usage?
Severe ATN may occur rarely, but the most common significant finding is a mild rise in plasma creatinine.
Is renal function impairment from aminoglycoside reversible?
Almost always b/c the proximal tubular cells have the capacity to regenerate.
How does renal toxicity correlative with aminoglycoside usage?
Toxicity correlates with the total amount of drug administered. SO ATN is more likely to be encountered with longer courses of therapy.
What is the most important result of renal toxicity from aminoglycosides?
Reduced excretion of the drug, which, in turn, predisposes to ototoxicity.
