Term
| What are aminoglycosides derived from? |
|
Definition
| Micromonospora and Streptomyces |
|
|
Term
| How are aminoglycosides named in relation to their derivative? |
|
Definition
Micromonospora--micin, ex. gentamicin
Streptomyces--mycin, ex. tobramycin |
|
|
Term
| What are the semisynthetic derivatives? |
|
Definition
| amikacin (semisynthetic) from kanamycin (natural) |
|
|
Term
| What "problem organisms" are aminoglycosides effective against? |
|
Definition
| pseudomonas and acinetobacter |
|
|
Term
| What are aminoglycosides synergistic with? |
|
Definition
| beta-lactams and glycopeptides |
|
|
Term
| Which two aminoglycosides get the most use in the USA for systemic infections? |
|
Definition
| gentamicin and tobramycin |
|
|
Term
| What is amikacin reserved for? |
|
Definition
| when there are strains of bacteria resistant against gentamicin and tobramycin |
|
|
Term
| What was amikacin specifically designed for? |
|
Definition
| to be "immune" to bacterial resistance mechanisms |
|
|
Term
| When is streptomycin used? |
|
Definition
| when there is a specific need for the drug (like a resistant strain of TB) |
|
|
Term
| What organisms does streptomycin treat? |
|
Definition
| enterococcus, mycobacterium (TB), plague |
|
|
Term
| What does spectinomycin treat? |
|
Definition
|
|
Term
| What is spectinomycin considered? |
|
Definition
|
|
Term
| When is spectinomycin used in treatment? |
|
Definition
| When a patient has an allergy to penicillins and has gonorrhea |
|
|
Term
| How is neomycin used (in what forms)? |
|
Definition
| topical agent in ointments, ophthalmologic products when combined with other antibiotics and steroids |
|
|
Term
| Why is neomycin used only topically? |
|
Definition
| it is very toxic, do not want it absorbed systemically |
|
|
Term
| Besides use as a topical agent, how else is neomycin sometimes used? |
|
Definition
tablets used for GI cleansing before surgery (like colorectal surgery)
still not used much |
|
|
Term
| Describe the chemical structure of aminoglycosides |
|
Definition
| two or more aminosugars bound by glycosidic linkages to a central hexose nucleus |
|
|
Term
| Describe the chemistry of the aminoglycoside molecule |
|
Definition
|
|
Term
| How is the aminoglycoside absorption? |
|
Definition
|
|
Term
| What is the aminoglycoside distribution in the body? |
|
Definition
low penetration into CSF and bronchial secretions
do not cross biologic membranes |
|
|
Term
| Are aminoglycosides good for meningitis? |
|
Definition
| no, not good penetration into CSF |
|
|
Term
| How are aminoglycosides used for respiratory infections? |
|
Definition
| always used in combination for respiratory infections. aminoglycosides broaden coverage but they don't have great penetration/concentration in bronchial secretions |
|
|
Term
| How is the pharmacokinetics similar between aminoglycosides? |
|
Definition
| blood curves very similar/almost identical so dosing would be the same |
|
|
Term
| How is the absorption of aminoglycosides through the gastrointestinal tract? |
|
Definition
| only about 1% absorption, very poor, won't get to infection effectively |
|
|
Term
| If a patient has a systemic infection and needs an aminoglycoside, how do they have to take it? |
|
Definition
|
|
Term
| When are adequate serum concentrations acheived with aminoglycosides? |
|
Definition
| parenteral administration |
|
|
Term
| Do aminoglycosides get bound by proteins? |
|
Definition
| no, all the drug that you put in is "free" drug |
|
|
Term
| What were the goals when developing aminoglycosides? |
|
Definition
wanted more pseudomonal activity
didn't want resistance with enterobacteriaceae
wanted less toxicity |
|
|
Term
| Which aminoglycoside is the most toxic? |
|
Definition
|
|
Term
| Which aminoglycosides show the least amount of toxicity? |
|
Definition
streptomycin
spectinomycin |
|
|
Term
| Which aminoglycosides don't show rapid resistance enterobacteriaceae? |
|
Definition
neomycin
kanamycin
gentamicin
tobramycin
amikacin
netilmicin |
|
|
Term
| Which aminoglycosides show antipseudomonal activity? |
|
Definition
gentamicin
tobramycin
amikacin
netilmicin |
|
|
Term
| Where are therapeutic concentrations acheiveable? |
|
Definition
| bile, bone, synovial spaces |
|
|
Term
| What is the metabolism of the aminoglycosides? |
|
Definition
no metabolites
aminoglycosides not changed by liver |
|
|
Term
| How are aminoglycosides eliminated? |
|
Definition
| kidneys via glomerular filtration |
|
|
Term
| Do you have to care about a patient's kidney function with aminoglycosides? |
|
Definition
| Yes, must monitor blood levels, may have to adjust dosing |
|
|
Term
| For a patient with normal kidney function what is the aminoglycoside half-life? |
|
Definition
|
|
Term
| How are the aminoglycoside's concentrations in the urine? |
|
Definition
very good for UTIs
may reach up to 100x serum levels |
|
|
Term
| Where do aminoglycosides accumulate in the body and what does this account for? |
|
Definition
accumulate in renal cortical tissue
accounts for nephrotoxicity |
|
|
Term
| What is inherent in the aminoglycosides? |
|
Definition
|
|
Term
| What are all aminoglycosides removed by? |
|
Definition
| hemodialysis (33-50%) and to a lesser degree by peritoneal dialysis |
|
|
Term
| Why do serum levels need to be monitored and doses adjusted? |
|
Definition
assure effective concentrations
minimize toxicity
aminoglycosides have a narrow therapeutic window |
|
|
Term
|
Definition
acute tubular necrosis
damage to kidney tubules, can regenerate
damage is reversible as long as it's not too bad |
|
|
Term
|
Definition
hearing loss (high pitch first)
hair cells damaged
vestibular damage (ataxia)
cochlea damaged
tinnitis |
|
|
Term
| Is the aminoglycoside ototoxicity reversible? |
|
Definition
| No, generally irreversible |
|
|
Term
| Are aminoglycosides bactericidal or bacteriostatic? |
|
Definition
|
|
Term
| Is the killing effect of aminoglycosides time dependent or concentration dependent? |
|
Definition
|
|
Term
| What are the three steps to aminoglycoside transport? |
|
Definition
1. AG's diffuse through the aqueous porin channels of the outer membrane of gram - bacteria
2. AG's actively transported across the cytoplasmic membrane
3. AG's bind to ribosomes and inhibit protein synthesis |
|
|
Term
| What is the rate-limiting step to aminoglycoside transport? |
|
Definition
| step 2. AG's actively transported across the cytoplasmic membrane |
|
|
Term
| What inhibits the process of AG's being actively transported across the cytoplasmic membrane? |
|
Definition
| divalent cations, hyperosmolarity, pH reduction, anaerobiasis |
|
|
Term
| What organisms are aminoglysocides completely ineffective against and why? |
|
Definition
| anaerobes--because they lack the active transport mechanisms to bring AGs across the cytoplasmic membrane |
|
|
Term
| Is the aminoglycoside binding to ribosomes reversible? |
|
Definition
| binding is very tight, perhaps irreversible |
|
|
Term
| Where is antimicrobial inhibition most pronounced? |
|
Definition
| 30S subunit of the ribosome |
|
|
Term
| Once an AG is bound to the ribosome what changes have been observed? |
|
Definition
cell wall permeability and transport changes
inhibition of protein synthesis
misreading of the genetic code |
|
|
Term
| What are the three bacterial mechanisms of resistance? |
|
Definition
altered target site of action
resistance due to decreased drug uptake
plasmid-mediated production of inactivating enzymes |
|
|
Term
| Which organism more commonly uses an altered target site of action for resistance? |
|
Definition
|
|
Term
| What organism has shown resistance due to decreased drug uptake? |
|
Definition
|
|
Term
| What are the inactivating enzymes? |
|
Definition
| acetylases, phosphorylases, adenyl transferases |
|
|
Term
| What do the inactivating enzymes do? |
|
Definition
| add chemical moities that prevent the proper working of the drug |
|
|
Term
| What is the most common form of resistance against AGs? |
|
Definition
| plasmid-mediated production of inactivating enzymes |
|
|
Term
| What accounts for the unpredictability of susceptibility testing of aminoglycosides? |
|
Definition
| plasmid-mediated production of inactivating enzymes |
|
|
Term
| Which aminoglycoside is designed to have the fewest vulnerable points of interaction? |
|
Definition
|
|
Term
| What organisms do aminoglycosides have moderate activity against in combination with a beta-lactam or a glycopeptide? |
|
Definition
gram + aerobes
Staph (including MRSA), Strep viridans, Enterococci |
|
|
Term
| What organisms do aminoglycosides have good activity against? |
|
Definition
gram - aerobes
E. coli, Klebsiella, Pseudomonas, Acinetobacter, most others |
|
|
Term
| What is the strength of aminoglycosides? |
|
Definition
gram - aerobes
(ex. PESKY-MESS, SPACE bugs, etc.) |
|
|
Term
| What are aminoglycosides poor against? |
|
Definition
|
|
Term
| What is traditional dosing? |
|
Definition
peaks and troughs
wanted to keep concentration above MIC longer |
|
|
Term
| What occurred after the 3rd dose in traditional dosing? |
|
Definition
|
|
Term
|
Definition
| try to get to steady-state right away |
|
|
Term
| What does extended interval (once daily) dosing take advantage of? |
|
Definition
| concentration dependent killing |
|
|
Term
| What is the post-antibiotic effect? |
|
Definition
| bacteria are "stunned" by large dose and it takes them a while to recover |
|
|
Term
| How does the effectiveness vary among the aminoglycosides? |
|
Definition
| against susceptible pathogens all aminoglycosides are equally effective |
|
|
Term
| How do toxicities vary among the aminoglycosides? |
|
Definition
| toxicities are approximately the same |
|
|
Term
| What are aminoglycosides especially active against? |
|
Definition
| all aminoglycosides are especially active against enterobacteriaceae |
|
|
Term
| Which AG is most active against P. aeruginosa? |
|
Definition
| tobramycin is 2-4x more active against P. aeruginosa than gentamicin |
|
|
Term
| Which AG is most active against enterobacteriaceae? |
|
Definition
| gentamicin is more active than tobramycin against enterobacteriaceae |
|
|
Term
| What is the most active AG against gentamicin-resistant strains? |
|
Definition
|
|
Term
| What is sometimes used against S. aureus? |
|
Definition
| antistaphlococcal penicillin's and gentamicin are synergistic against it |
|
|
Term
| What is used against enterococci? |
|
Definition
| gentamicin + ampicillin are synergistic if the enterococci does not exhibit high levels of resistance to the aminoglycoside |
|
|
Term
| What agent is used against M. tuberculosis? |
|
Definition
|
|
Term
| What agent is used against M. avium-intracellulare? |
|
Definition
|
|
Term
| What agent is used against nocardia? |
|
Definition
|
|
Term
| Aminoglycosides vs other classes of antibiotics |
|
Definition
| beta lactams and flouroquinolones are safer and preferred if susceptibilities allow them to be used |
|
|
Term
| Where are aminoglycosides still important? |
|
Definition
| still important in combination therapy in serious infections caused by serious Pseudomonas aeruginosa and Enterococcal infections |
|
|
Term
| What is less of a problem with aminoglycosides compared to other classes of antibiotics? |
|
Definition
|
|
Term
| What is more of a problem with aminoglycosides compared to other classes of antibiotics? |
|
Definition
|
|
Term
| What percentage of patients will develop some toxicity? |
|
Definition
|
|
Term
| What is important to remember about AG toxicity? |
|
Definition
|
|
Term
| Under what conditions are AGs less active? |
|
Definition
|
|
Term
|
Definition
|
|
Term
| Where do aminoglycosides have a more prominent role? |
|
Definition
| nosocomial infections, especially P. aeruginosa |
|
|
Term
| Why is aminoglycoside use limited in the community? |
|
Definition
| bacteria are likely to be susceptible to other antibiotics |
|
|
Term
| When are AGs used to modify the initial therapy? |
|
Definition
| used in life-threatening community acquired infections of unknown etiology |
|
|
Term
| Which AGs have similar toxicity profiles? |
|
Definition
| gentamicin, tobramycin, and amikacin |
|
|
Term
| What are the adverse effects from AGs? |
|
Definition
neuromuscular paralysis
ototoxicity
nephrotoxicity |
|
|
Term
| What are some alterable risk factors that predispose a patient to AG toxicity? |
|
Definition
diuretics
radiographic contrast dyes
effective circulating volume depletion
ACE inhibitors
NSAIDs
concomitant use of amphotericin B
cisplatinum |
|
|
Term
| What are some unalterable risk factors that predispose a patient to AG toxicity? |
|
Definition
age
pre-existing renal disease |
|
|
Term
| How are aminoglycosides always used? |
|
Definition
|
|
Term
| Indications of use for aminoglycosides |
|
Definition
initial therapy of seriously ill patients, particularly febrile patients with neutropenia
treatment of multi-drug resistant gram - bacilli
polymicrobial infections
synergism may occur when treating P. aeruginosa, S. aureus endocarditis or bacteremia, enterococcal endocarditis |
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|
