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Aminoglycosides, Linezolid, Daptomycin, Trimeth-Sulfa, Nitro
Last of the anti-bacterials... why so many??? 11% my behind need to study some ICS
49
Pharmacology
08/24/2010

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Term
Aminoglycoside MOA
Definition
irreversible inhibition of protein synthesis,
binds 30s subunit of bacterial ribosome, blocking the initiation of peptide syntheis
Term
Entry of Aminoglycosides into gram (-) cell
Definition
requires active transport via an oxygen dependent process with a proton gradient, low pH or low O2 decreases cell membrane transport
Term
synergism and aminoglycosides
Definition
PCN's, cepsh and vanc make it easier for AG's to penetrate
Term
T/F, aminoglycosides are cidal?
Definition
TRUE, despite being protein systh inh,they are cidal
Term
Spectrum of Aminoglycosides
Definition
mostly gram (-) but will cover gram + if used with an inh of cell wall synth
Term
Can you use an AG alone in a G+ inf
Definition
NO
Term
Treatment of staph, strep or entero endocarditis
Definition
low does AG plus B=lactam or Vanc
Term
What are the AG drugs
Definition
streptomycin,
neomycin
kanamycin
paromomycin
gentamicin
tobramycin
amikacin
netilmicin
spectinomycin
simoci
dibekacin
isepamicin
Term
Elimination of gentamicin
Definition
Renal only so reduce dose in renal failure, or give something else
Term
Dosing of AG's
Definition
High dose G(-) 1.5mg/kg q12
Low does G(+) 2-2.5 mg/kg q12
MUST adjust for body weight as AG's do NOT distribute to fat
Term
Do AG's exert conc dep killing
Definition
YES, and exert post antibiotic effect
Term
toxicity of AG's
Definition
both time and conc dependent
Nephrotoxicity usually reversible
Ototoxicity - irreversible
Term
contraindicated drugs with AG's
Definition
amphotercin B, cyclosporines, Vanc, and NSAIds increase the likelihood of nephrotoxicity
Term
AG, ototoxicity
Definition
Gent primarily vestib damage
Term
Big contraindicative for AG's
Definition
furosemide, often given to maintain urinary output, is also toxic to the VIII cranial nerve
Term
Mechanisms of AG resist
Definition
most common = drug alteration, addition of ph, adenyl, acteyl
decreased transport into cell - pseudo has 40 efflux pumps
changes in 30s binding site
Term
ace in the hole for bacteria resistant to gentamicin or tobramycin
Definition
****Amikacin****
Term
AG absorption
Definition
poor GI abs, must be given iv for systemic infections
Term
Common topical AG in ear drops eye drops and ointments
Definition
Gentamicin
Term
Drug given PO to decontaminate the gut prior to surgery
Definition
Neomycin
Term
Linezolid coverage
Definition
Excellent G + covers MRSA, VRA, PCN res strep pneumo
Minimal Gram (-) activity
Term
Linezolid MOA
Definition
binds unique site
23S ribosomal RNA OF
50S subunit blocking assembly of 70s
Term
Is linezolid static or cidal?
Definition
Statis
Term
Bioaval of linezolid
Definition
100%
Term
Linezolid weaknesses
Definition
STATIC esp with MRSA and VRE
poor for endocarditis or osteomyelitis
Expensive comp to vanc
contraindicated with SSRI's since it is a MAOI
periph neuropathy and irrev optic neuritis
Term
Reversible bone marrow depression side effect
Definition
Linezolid 25% platelet decrese in 10 days
Term
Daptomycin MOA
Definition
unknown bu appears to depolarize the cell resulting in loss of potassium and cell death
Term
Dapto cidal or static?
Definition
Cidal with conc dependent cidal activity
Term
Therapeutic uses of Daptomycin
Definition
MRSA in patients who can't handle vanc
VRE including E. faecalis
Term
Can you use Dapto for SSTIs or MRSA pneumo
Definition
NO, inactivated by surfactant
Term
Detailed MOA of Trimeth Sulfa, which acts where?
Definition
Sulfamethoxazol acts first to inhibit dihydropteroate synthase so NO DHR dihydro
trimeth acts second to inhibit DHfolate reductase so NO THF
PABA is the precursor to DHF and DHF to THF
Term
What is THF used for and what drug(s) block it's synth
Definition
used to make purines and amino acids, trimeth blocks THF synth, and sulf block DHF
Term
Competitive agonist of PABA
Definition
Sulfamethoxazole, thus inhibits dihydropteroate synt to prevent synth of DHF
Term
DOC for treatment of Pneumocystis jiroveci
Definition
Trimeth Sulfa
Term
Spectrum of Trimeth sulfa
Definition
Staph including MRSA
Entero in ICU
E.coli and Klebsiellas
Term
Bugs Resist to Trimeth sulfa
Definition
Pseudomonas, enterococci, or bacteroides
Term
Weaknesses on trim-sulfa coverag
Definition
Does NOT cover group A streptococcus. For SSTIs, use either po cephalexin or po amoxicillin with po trimsulfa
Term
Trim-sulfa side effects: lots
Definition
severe allergic reacion in skin, photosens, fever, uticaria,
Stevens Johnson syndrome - severe erythema multiforme with mucous mem involvement
Toxic epidermal necrolysis - full thickness epidermal necrosis with widespread skin loss
Term
Problem in older men being treated with trim-sulfa
Definition
hyper kalemia
Term
Treatment for uncomplicated UTIs
Definition
trim-sulfa
Term
How to treat outpatient MRSA infections?
Definition
Clinda is preferred over trim-sulfa b/c clinda covers staph a and b.trimsulfa does not cover GAS and doxy does not cover GBS
Trim sulfa works well in the treatment of MRSA abcesses after drainage
Term
Treatment of inpatient MRSA
Definition
For SSTIs clinda, trim-sulfa, or doxy, latest UH reg is doxy +i.v. cefazolin
Vanc for severe MRSA inf or crit ill patients
Linezolid for patients who can't handle Vanc, or uncomplicated MRSA inf
Term
Second line drug for MRSA bacteremia behind Vanc
Definition
Daptomycin
Term
Doc for infections caused by Nocardia spp in immunocompromised patients
Definition
Trim-sulfa
Term
DOC in ICU infections by Stenotroph malt resistant bact
Definition
trim-sulfa
Term
MOA of Nitrofurantoin
Definition
Bacterial enzymes rapidly reduce nitrofur to a ractive intermed which damages DNA to cause cell death
Term
Nitrofurantoin Cidal or Static
Definition
static at low concentrations
cidal at high concentrations
Term
Drugs that are safe to use in Pregnant women
Definition
Nitrofurantoin, amoxacillin and cephalexin
Term
Weakness of Nitrofurantoin
Definition
CANNOT be used to treat pyelonephritis or prostatitis limited to the urine
turns urine brown
S/E's hepatitis, neuropathies, and pulmonary fibrosis after long term treatment for UTI's