Aminoglycosides
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| Aminoglycosides Drugs ? | * Gentamicin --- Amikacin --- Tobramycin --- Streptomycin --- Neomycin
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| Basic MOA ? | * Protein Synthesis Inhibitors acting at the 30S ribosome
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| Aminoglycosides (AGs) basics ? | * Most commonly used in Gram (-) Aerobes ..... * Always used in combo, usu b-lactams ..... * Use is limited due to severe toxicity
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| AGs most Cx use ? | * empiric therapy of serious infections, when we think it is a severe G (-) bacteria.... * use in hospital bc given IV and once the culture is done, an appropriate drug is used
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| AGs spectrum of activity to use in ? | * Serious infections by aerobic G- bacilli, including Pseudomonas, Proteus, Serratia, and G+ Staph .... * Used in b-lactam combo for Pseudomonas, Invasive enterococcal infections and Serious Stap.
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| When AGs can be used as a monotherapy ? | * Tularemia - Plague - UTIs
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| Gentamicin basics and use ? | * one of the most used AGs ..... *Usually used in combination with a cillin for severe infections: Pseudomonas (a DOC) -- Enterococcal (a DOC)...... *
Enterococcal endocarditis and tularemia
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| Amikacin unique features and uses? | * Primarily used for pseudomonas and other serious infections caused by organisms resistant to other AGs..... * broadest spectrum due to its unique metabolism
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| Streptomycin use ? | * Used as single agent to treat tularemia and plague
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| Neomycin use ? | * primarily OTC drugs.... * primarily for gut sterilization before surgery
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| Aminoglycosides – MOA ? | * Irreversibly binds to 30S ribosome -->
interferes with initiation complex formation
--- causes misreading of mRNA ---
restricts polysome formation ..... * Unique bc it is Bactericidal
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| AG drug resistance is common in ? | * Especially a problem for enterococci
, due to AME (Aminoglycoside Modifying Enzyme)
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| AG Pharkokinetics ? | * Must know and monitor kidney function (CrCl) bc they are eliminated by glom. filtration in the kidneys....* so adjust dose based on kidney monitoring
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| AGs Dosing ? | * Intermittent Dosing - 3 x a day small doses and Extended Dosing - 1 time a day
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| Extended Dosing Advantages ? | * compariable outsomes to intermittent, seems to be better on the kidneys, don't have to monitor serum levels of the drug as much,
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| Extended Drug Dosings 2 advantages ? | * Post-antibiotic effect (PAE)
and Concentration-dependent killing ....* basically, more drug is on board, so it will kill more and since we have PAE (post antibiotic effect), we still get killing after concentrations drop below the MIC
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| How is it less toxic ? | * Bc it is time and concentration dependent.... * get less drug accumulation due to the once a day dosing
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| When not to use extended AG dosing ? | * Pts w/ unstable renal function
--- CrCl < 60ml/min
--- Endocarditis or meningitis
--- Increased Vd (pregnancy, ascites, edema)
--- Pts receiving concurrent nephrotoxic or ototoxic drugs
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| AGs SEs ? | * Very low TI .....* Can cause ireeversible Ototoxicity, reversible neuromuscular block (CI in myasthenia gravis), and causes Nephrotoxicity
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| Why we see the SEs ? | * the more you use the drug, the more likely it is to have a SE.... * Ototoxicity is due to it being trapped in the endolymph
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| TmT for AGs Toxicity ? | * IV Calcium Salts
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| *b-Lactam Drugs* --> Monobactams --> Aztreonam basics ? | * Effective against gram negatives only
...... *Same mechanism of action as other b-lactams by only binds to a PBP (penicillin binding protein) present in gram negatives
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| Aztreonam uses ? | * Almost the same use as AGs ...... *serious gram negative aerobes infections --> Pseudomonas (DOC), Enterobacter........ * Good for MDR pseudomonas and for those with a penicillin allergy
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| Streptogramins --> quinupristin + dalfopristin MOA ? | * Protein Synthesis Inhibitors acting at the 50S ribosome
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| Quinupristin + Dalfopristin use ? | * Always used in combo with each other...... * Drug resistant G+ cocci infections like Staph. or Entero Faecium that is Vanc resistant (VREF)
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| Quinupristin + Dalfopristin SEs ? | * myalgias and inhibit p450s
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| Urinary Antiseptic --> Nitrofurantoin basics ? | * a very rapidly excreted drug that is used exclusively in uncomplicated UTIs....* not a first line drug....* also can be used for reoccurring/chronic UTIs
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| Nitrofurantoin MoA ? | * ROS that damages DNA... * true MoA not really known
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| Nitrofurantoin SEs ? | * Hypersensitivity reactions - skin rashes..... * Causes Hemolytic anemia in G6PD deficiency...... * Acute pneumonitis in Elderly..... * Turns the Urine BROWN
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