Aminoglycosides Test Questions

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What are the commonly used AG in clinical practice?
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1. Gentamicin
2. Tobramicin
3. Amikacin
4. Streptomicin
5. Neomycin (topically used)
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What is the MOA of AG?
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1. Inhibit protein synthesis by irreversibly binding to bacterial ribosomes 30S, interfering with translational accuracy of mRNA
2. Other mechanisms include cell wall activity via ionic interactions with the cell wall
3. They have been shown to disrupt and leave holes in the cell wall causing “bacterial bleeding”
4. In most cases, AG are CIDAL
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How much toxicity from the AG are we going to accept?
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The amount of toxicity we are willing to accept depends on the severity of the infection
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Is renal dysfunction caused by AG reversible?
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For the most part, renal dysfunction is reversible
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AG calculations are based on what compartment model?
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Calculations are usually based on a 1-compartment model
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AG display what kind of compartment kinetics?
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AG display 2-3 compartment kinetics so when monitoring levels, there is a need to avoid 1st and 3rd distribution phases unless using QD dosing
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With AG, which has higher concentrations? Tissue or serum?
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Concentrations in the tissue are lower that in the serum
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Can AG penetrate the CSF?
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CSF penetration is poor
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AG display what kind of killing?
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AG and QN display concentration dependent killing, so the higher the concentration, the better the kill
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Does AG have post-ab effect?
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Yes, but the duration of the post-ab effect is organism dependent and dose dependent
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How long is the half-life of AG?
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T1/2 = 2 hrs in patients with normal kidney function

T1/2 = 0.693/Kd

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What is the Vd of AG?
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Vd = 0.25-0.4 L/kg based on IBW (use ABW if obese)
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Dose AG distribute into adipose tissues?
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No, the Vd is similar to ECF and distributes poorly into adipose tissue
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How do you calculate Vd in obese patients?
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Vd = 0.25L/kg

ABW = IBW + 0.4(Actual – IBW)

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What is the relationship between AG and CrCl?
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AG clearance is proportional to GFR (CrCl)
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Is AG dialyzable?
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Yes, can be removed by hemodialysis, peritoneal dialysis & continuous hemofiltration (membranes determine quantity removed per unit of time on dialysis)
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If greater than 65 yo, which SCr do you use?
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Minimum SCr = 1
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How do you calculate the elimination rate constant?
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Kd (hr-1) = CL (L/hr)/Vd (L)
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How do you calculate a LD for AG?
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LD = (desired AG serum conc.) CPss * Vd
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Why do we base dosing off of lean body tissue (IBW)?
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Because AG are based off a 1 compartment model (water) and most of the water are in muscle
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Can AG be used in combo or as monotherapy?
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Usually used as part of a combination that is synergistic and in rare cases, can be used alone as monotherapy like in uncomplicated UTI
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What is the spectrum of activity of AG?
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1. Gram (-) organisms:
Enterobacteriaceae
Pseudomonas aeruginosa
Serratia
M. tuberculosis
Mycobacterium Avium (MAC)
SPACE
2. Gram (+) organisms:
Enterococci
Streptococci
Staphylococci
Listeria
(do not cover strict anaerobes without facilitation)
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Why can AG be used as monotherapy in treatment of uncomplicated UTI?
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Bc AG are highly concentrated in the kidneys and so are highly concentrated in the urine (drug can be concentrated ip to 50 times in the urine — AG + water)
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For gram (+) organisms, which of the AG are more potent?
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Gentamicin!
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For gram (-) organisms, which of the AG are more potent?
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Tobramycin!
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Which AG is MOST potent in general?
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Amikacin!
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When using AG, which are the toxicity concerns we have?
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1. Nephrotoxicity (associated with trough levels)
2. Ototoxicity (associated with peak levels)
3. Neuromuscular blockage
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Is nephrotoxicity reversible? And when is the onset of nephrotoxicity induced by AG?
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Usually reversible, occurs 5-7 days after therapy
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Why does nephrotoxicity occur?
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Bc AG have high affinity for proximmal tubule cells and may cause ATN and proximal tubular injury and cell necrosis
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What are the risk factors for ATN?
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1. Long duration of treatment
2. Trough levels > 2mg/L and time
3. Repeated courses within a few months
4. Elderly >/= 65 yo
5. Malnutrition
6. Volume depletion
7. Pre-existing liver/renal disease
8. Potassium/magnesium depletion
9. Other nephrotoxic drugs
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Is ototoxicity reversible?
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Usually irreversible
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What are s/sx of ototoxicity?
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Tinnitus or feeling of fullness in the ears (don’t complain of hearing loss until significant damage is done)
– Vestibular: N/V, cold sweats, nystagmus, vertigo
– Watch w/ concommitant ototoxic agents (Loop D, erythromycin)
– Watch w/ close-proximity ototoxic agents Platinum agents, Vinca’s
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How does AG affect neuromuscular blockage?
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AG prolongs neuromuscular blockage
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What are the risk factors for AG-induced neuromuscular blockage?
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1. Concurrent neuromuscular blockers
2. CCB
3. Electrolyte abnormalities
4. Myasthenia Gravis
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What are the clinical uses of AG?
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1. Gram (-) nosocomial pneumonia
2. Bacteremia
3. Pyelonephritis
4. Urosepsis
5. Sepsis
6. Polymicrobial infections
7. Febrile neutropenia
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How can we cover Enterococcus with AG?
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In combo with beta lactams (PCN or Amp) – gent preferred (Gram (+) = Gent; Gram (-) = Tobra)
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What can we use for Enterococcus resistance?
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1. Vancomycin (Vancocin)
2. Linezolid (Zyvox)
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How do you treat coagulase (-) staph endocarditis?
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Combo with vanco and rifampin
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How do you treat staph. aureus endocarditis?
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Combo with antistaph PCN with AG
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What is the usual dosing intervals for AG?
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Usually 8-12 hrs, sometimes 24 with poor renal function
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What is the dosing for urinary, tissue, lungs/blood
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1. Urinary: 1mg/kg (5) synergistic dose
2. Tissue: 1.5mg/kg (6) moderate infection
3. Lung/blood: 2mg/kg (7) moderate/severe infections
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When are drug levels usually obtained?
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– Usually obtained after the 3rd dose
– Peak: obtain 30 min after a 30 min infusion or 15 min after 60 min infusion
– Trough: Just prior to the 4th dose
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What are the peak targets for gent/tobra and amikacin?
answer

1. Gent/Tobra peak
UTI: 3-5 mcg/mL
Skin & soft tissue infections: 5-7mcg/mL
Pneumonia & sepsis: 7-10 mcg/mL
2. Amikacin
UTI: 20 +/- 5 mcg/mL or 25
Skin & soft tissue infection: 25 +/- 5 mcg/mL or 30
Pneumonia & sepsis: 30 +/- 5 mcg/mL or 35
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What are the trough levels we want?
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1. Gent/Tobra: <2 mcgml
2. Amikacin: <10 mcg/mL
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What is the maximum peak for Gent?
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<10 mcg/mL
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Why do we use High dose, once daily dosing?
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1. Optimize PK/PD properties
2. High dose therapy is less nephrotoxic
3. Resistance
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For once daily dosing, what is the peak for Gent/Tobra and Amikacin?
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1. Gent/Tobra = 20 mcg/mL
2. Amikacin = 60 mcg/mL
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What is the once daily dose for Gent/Tobra and Amikacin?
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1. Gent/Tobra = 7 mg/kg
2. Amikacin = 15 mg/kg
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What is the dosing interval for once daily AG?
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CrCl >60: Q24 hrs
CrCl 40-59: Q36 hrs
CrCl 20-39: Q48 hrs
CrCl < 20: monitor serial levels
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How do you monitor once daily AG levels?
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Random conc after the 1st does between 6-12 (14) hr after the start of the infusion
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How long do we infuse once daily AG?
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Infusion is usually over 60 min
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When is once daily dosing not recommended for?
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1. Enterococcal endocarditis
2. Pregnancy
3. Select pediatric populations
4. Cystic fibrosis
5. Burns (Vd is unpredictable)
6. Renal failure (CrCl<10ml>
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High level Gent resistant enterococcus may be sensitive to what other AG?
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Streptomycin
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Synergy doses do not require levels…what does this mean??
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Everyone gets 1mg/kg, and no body gets level bc you are not using it for peak/trough, you are just using it for synergy dose
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How do you treat abscess?
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You need to drain abscess bc AG can’t perfuse in there (can only penetrate tissues)
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When should drug levels be obtained after hemodialysis?
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2 hrs after hemodialysis
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Is monitoring necessary for patients with normal renal function who will be on therapy for <5 days?
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Not really
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What do you do for patients with ascites/edema?
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For ever 1 kg of weight gained, you need to increase Vd by 1 L (look at I/O)
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Is it ok to add PCN along with AG in the same IV bag?
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No! You can NEVER let antipseudomonal PCN or ANY PCN come into contact with AG
bc can inactivate AG (Gent/Tobra are more problematic than Amikacin)
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When on AG therapy, which lab value do you need to monitor daily?
answer

SCr

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