Aminoglycosides Erdman

Question 1

Special consideration

Answer 1

First group of antibiotics that are dosed individually for each patient and require serum concentration monitoring due to Vd and Cl and the narrow therapeutic range

Question 2

Chemistry

Answer 2

Consist of 2 or more amino sugars linked to an aminocyclitol ring by glycosidic bonds

Very polar, not capable of crossing lipid membranes

Question 3

Class generalizations

Answer 3

Agents -tobramycin, gentamycin, amikacin, streptomycin
Bactericidal - concentration dependent (except static against enterococcus) –to get cidal effect against enterococcus, use with gentamycin!

All have post antibiotic effect
Bind irreversibly to 30S ribosomes to inhibit protein synthesis, misreading of mRNA

**only good against aerboes

Question 4

Gram + coverage

Answer 4

Always used in conjunction with a cell wall agent
Aerobes only

Gentamycin is pretty good and it covers MRSA and MSSA (target), viridans strep, and enterococcus

Streptomycin will be used for enterococcus if gentamycin can not be used

Question 5

Gram - coverage

Answer 5

Often used with a cell wall active agent
Aerobes only
High activity against gram negatives (A>T>G)

PEKSSS

Pseudomonas aeruginosa (A>T>G) (target)
Need to get peak ration of 10:1

Question 6

Dosing Pharmacology

Answer 6

Must be parenteral because poorly absorbed by GI due to polarity
Intermittent IV infusion is preferred (30m-1h) , although IM can be used –continuous infusion is not used because we need to achieve a high peak!

Question 7

Distribution

Answer 7

POORLY distribute to CSF, lungs, and adipose tissue

Question 8

Dosing

Answer 8

Use LBW (ADW in obese) for dosing
Volume status must be taken into account to calculate appropriate dose (normal Vd = 0.25L/kg)
Large Vd (>.3) in pregnancy, CHF, ascites, burn patients, and neonates
Small Vd (<.2) is due to dehydration

Question 9

Elimination

Answer 9

Eliminated unchanged by kidneys

Half life depends on renal function, but is usually 2.5-4 hours

Question 10

Concentration Monitoring

Answer 10

Peak drawn 30(standard) or 60(large or delayed dose) minutes after the END of infusion of 3rd dose

Trough is drawn prior to next dose

Need to verify when a draw was obtained to verify accuracy

Question 11

Gram + synergy dosing

Answer 11

1mg/kg (gent) using LBW or ADW

Question 12

Gram - dosing

Answer 12

Need a higher peak than positive, so it is 2-2.5mg/kg for gent or tobra using LBW or ADW

Question 13

Gent and Tobra Peak and Trough for Moderate infection

UTI

Answer 13

Peak 4-6mcg/mL
Trough 0.5-1.5

Not much needed because it is renally eliminated

Question 14

Gent and Tobra Peak and Trough for Moderate-severe infection (SSTI, bacteremia)

Answer 14

Peak 6-8mcg/mL

Trough 1-1.5

Question 15

Gent and Tobra Peak and Trough for Severe infection (pneumonia, burn, life threatening)

Answer 15

Peak 8-10mcg/mL

Trough t really penetrate lungs well

Question 16

Once daily dosing

Answer 16

ONLY for Gram - because concentration dependent not as important for positive activity…

Higher peaks and lower (undetectable) trough help decrease toxicity and take advantage of PAE

5-7mg/kg LBW or ABW q24hr (gent,tobra)
Peak 13-20 and trough 40mL/min)

Question 17

Toxicity

Answer 17

Neprotoxicity -increase in BUN and Cr, reversible.
Increased risk if prolonged high TROUGH (why she aims for 1) or additional nephrotoxic drugs like vanc)
Keep them well hydrated!

Ototoxicity -8th cranial nerve damage (vestibular and auditory) IRREVERSIBLE
Vanc and loop will increase risk. Must stop drug if developing ototoxicity. Other risks are same as nephrotoxicity