Aminoglycosides

Question 1

Common drugs

Answer 1

Streptomycin
Gentamicin
Tobramycin
Amikacin

Question 2

MoA

Answer 2

Irreversibly bind to 30S ribosomal subunit
Inhibition of protein synthesis
Cell entry is O2 dependent

Question 3

Mechanism of Resistance

Answer 3

Synthesis of AG modifying enzymes
Altered AG uptake (loss of porin channel, efflux pump)
Change in ribosomal binding site/target modification

Question 4

Parmacokinetics

Answer 4

Poor oral absorption
Low protein binding, high water solubility
Low in CSF, bronchial secretions, bile, vitreous humor
Pleural, pericardial, ascitic, and synovial fluid
High in urine (really good for UTIs)
99% renally eliminated, removed by hemodialysis
Linear PK

Question 5

Pharmacodynamics

Answer 5

Concentration dependent killing PK/PD

Want a high peak, will increase PAE

Question 6

Dosing

Gram- infections

Answer 6

Amikacin is dosed about 2-3 times what gent and tobra are
Concentration is about 2-3x higher than gent and tobra
Big hit, little exposure

Question 7

Dosing

Gram+ infections

Answer 7

No advantage to getting a higher peak
Still aim for small troughs to try and get drug out of kidney for safety
Strepto is ONLY used for Gram+

Question 8

Dosing

Mycobacterial infections

Answer 8

Looking at months of toxicity, so its better to give huge doses days apart
If pt develops ototoxicity just stop using aminoglycosides
If pt develops nephrotoxicity you don’t have to stop, just pull back on dosing (less frequently)

Question 9

Clinical Uses

Gram-

Answer 9

In combination with B-lactams to treat resistant/serious infections
Emiric treatment of sepsis (especially urinary)
Bloodstream, intraabdominal infections, SSTI
Use high dose for pneumonia
Rarely used at monotherapy

Question 10

Clinical Uses

Gram+

Answer 10

Mostly gent, some strepto
Use in combination with B-lactams (ampicillin or nafcillin) or vanco for severe infections (enterococcal or staph endocarditis)

Question 11

Clinical Uses

Mycobacterium

Answer 11

Amikacin, strepto

Use in combination with multiple antimycobacterial agents

Question 12

Toxicities

Answer 12

Nephrotoxicity (gent>tobra>amik>strepto), risk factors: prolonged/elevated trough concentrations, prolonged therapy, underlying renal insufficiency, advanced age, hypovolemia, concomitant nephrotoxins

Ototoxicity: cochlear (amik>gent>tobra) and vestibular damage (strepto>gent>amik>tobra). Usually irreversible. Risk factors: increased age, prolonged AG course, ?increased serum concentration, ?genetic factors