Aminoglycosides

Question 1

What formulations are aminoglycosides given for systemic infections?

Answer 1

IM or IV

Question 2

Nephrotoxicity Risk Factors

Answer 2

Increased Age
Preexisting renal insufficiency
Hypovolemia
Using other nephrotoxic agents
Liver disease

Question 3

What are some other nephrotoxic agents?

Answer 3

Amphotericin B
Furosemide
Vancomycin
Contrast dye

Question 4

Things you need to monitor while a patient is on aminogylcoside therapy?

Answer 4

Serum Creatinine
Liver enzymes/funtion
(BUN and Creatinine)

Question 5

What are normal Serum creatinine levels?

Answer 5

0.6-1.2 mg/dL

Question 6

What toxicities are you watching out for when you give a patient aminoglycosides?

Answer 6

Nephrotoxicity (reversible)

Ototoxicity (irreversible)

Question 7

Medications that are risk factors for ototoxicity

Answer 7

Loop diuretics

Vancomycin

Question 8

Where do aminoglycosides distribute?

Answer 8

Extracellular fluids (~25% of body weight) (0.25L/kg)

Not in fat, meninges, etc.

Question 9

What do you expect the volume of distribution of neonates and newborns to be of aminoglycosides?

Answer 9

I expect it to increase because they have more water/extracellular fluid.

Question 10

How long do we infusion IV?

Answer 10

30 minutes to 1 hour

Question 11

Is the protein binding high or low?

Answer 11

Low (10%)

Question 12

What model are the aminoglycosides (one, two, or three compartment)?

Answer 12

Three compartment, but treat as one.

Has Distribution, accumulation, and elimination phases.

Question 13

Why do we draw our peak levels 30 minutes before and after infusions?

Answer 13

To ignore the distribution phase and elimination phases. This allows us to treat the aminoglycosides as one compartment.

Question 14

How long does it take you to get to steady state?

Answer 14

3-5 half-lives

Question 15

What drives dose?

Answer 15

Volume of distribution

Question 16

What does renal function (creatinine clearance) drive?

Answer 16

Half-life

Question 17

What does half-life drive?

Answer 17

Dosing interval (tau)

Question 18

What is the aminoglycoside dosing regimen?

Answer 18

1. Estimate creatinine clearance
2. Estimate k and half-life
3. Estimate volume of distribution (V)
4. Choose desired steady state concentrations
5. Calculate dosing interval
6. Calculate loading dose
7. Calculate maintenance dose regimen

Question 19

What are common dosing intervals for aminoglycosides?

Answer 19

8, 12, and 24 hours

Question 20

What are your peaks and troughs for Genatmicin/Tobramycin?

Answer 20

Peaks:
5-10mg/L

Troughs:
0.5-2mg/L

Loading Dose:
1.5-2mg/kg

Question 21

What are your peaks and troughs for Amikacin?

Answer 21

Peaks:
25-35mg/L

Troughs:
4-10mg/L

Loading Dose:
5-7.5mg/L

Question 22

What is the conventional dosing for Gent/tobra and Amikacin?

Answer 22

1-2mg/kg

5mg/kg

Question 23

Conventional dosing interval?

Answer 23

Q8H

Question 24

What would you want your peak concentrations for UTI? What would you want for pneumonia?

Answer 24

Low end of peak (4-5)

Higher end (8-10)

Question 25

Vd on average, dehydrated, CHF (volume overload), peds patient, ascites, CF

Answer 25

Average=0.25
Dehydrated=0.2
CHF=0.3
Peds=0.5-0.6
Ascites=0.25+excess fluid
CF=0.4-0.45L/kg

Question 26

What is the half-life for aminoglycosides?

Answer 26

~2-2.5 hours

Question 27

What does rate of infusion equal?

Answer 27

Dose/Time

Question 28

If Rate of infusion is 200mg/hour, what is your dose if you infuse over 30 minutes?

Answer 28

Dose is 100mg

Question 29

If your dose is 500mg what is your rate of infusion if you infuse over 30 minutes?

Answer 29

Rate of infusion= 150mg/hour

Your dosing interval is q8h

Question 30

If target peak concentration is 10mg/L and you have a normal 70kg patient, what would you give as a loading dose?

Answer 30

(175mg) Round to 180mg

Question 31

When calculating k, what is the change in time if you draw levels 30 minutes prior to the dose and 30 minutes after infusion and you give q8h? You also infuse over 30 minutes.

Answer 31

The change in time=6.5 hours
Dosing interval minus 1.5
Infuse over 30 minutes, draw 30 minutes after, draw 30 minutes before.

Question 32

For once-daily dosing (ODA), how to you optimize the peak?

Answer 32

Optimize the peak to MIC ratios (ideally>10)

Question 33

What are the exclusion criteria for ODA (once-daily dosing)?

Answer 33

Large volume of distribution patients
Ascites
Buns
Pregnant patients
Dialysis patients
Pediatrics
CF
Patients with gram positive bacterial endocarditis

Question 34

For a standardized creatinine clearance of 40 or more what are the ODA dosing recommendations for Gent/Tobi and Amikacin?

Answer 34

Gent/Tobi:
5-7mg/kg

Amikacin:
15-20mg/kg

Question 35

For a standardized creatinine clearance of less than 40 what are the ODA dosing recommendations for Gent/Tobi?

Answer 35

3mg/kg

Question 36

What is the recommended infusion time for ODA?

Answer 36

30 minutes

Question 37

What is the goal peak and trough concentrations for ODA?

Answer 37

Peak:
10-20mg/L

Trough
Less than 1mg/L
(Burgess “undetectable”)

Question 38

What do you monitor for ODA?

Answer 38

Peaks for adequate dosing
Kinetics: Peak and random time

Trough: Accumulation and toxicity

Question 39

How long do you want to wait for ODA to draw peak levels?

Answer 39

A couple hours because it takes it longer to distribute.

Question 40

What are 4 things you need to calculate to adjust a dosing regimen?

Answer 40

k
Peak concentrations
Trough concentrations
Volume of distribution