Aminoglycosides

Question 1

Aminoglycosides

Answer 1

• Cidal antibiotic against G- pathogens
• Amino sugars attached in glycosidic links to an aminocyclitol ring
• Usually given IV

Question 2

Mechanism of Aminoglycosides

Answer 2

• Enter periplasmic space of G- bacteria through porin channels
• Pass through inner membrane by flowing down their electrochemical gradient
• Block Ca uptake into cholinergic nerve terminals → decreased ACh release → decreased muscle contraction

Question 3

Are they effective vs anaerobes? Why or why not?

Answer 3

No! Because anaerobes don’t have an electron transport chain to create an electrochemical gradient for the Aminoglycoside to travel down

Question 4

What other type of antibiotics are they often used synergistically with?

Answer 4

• β-lactams for synergism & G+ coverage

Question 5

What is the mechanism of this synergism?

Answer 5

By inhibiting cell wall synthesis, β-lactams facilitate

penetration of aminoglycosides

Question 6

Where do Aminoglycosides attain their highest levels?

Answer 6

• Renal cortex → nephrotoxicity

* Endolymph of inner ear → ototoxicity

Question 7

Gentamicin

Answer 7

• IV Aminoglycoside
• Topical for burns, wounds, prevent infection
• Ophthalmic for superficial ocular infections

Question 8

Tobramycin

Answer 8

• IV Aminoglycoside

* Possibly less ototoxic than gentamicin

Question 9

Amikacin

Answer 9

• IV Aminoglycoside
• Enzyme resistant
• For nosocomial infections that resist gentamicin and tobramycin

Question 10

Neomycin

Answer 10

• Oral Aminoglycoside
• Used to prep for bowel surgery
• Topically as antiinfectant

Question 11

Paromomycin

Answer 11

• Oral Aminoglycoside

* Used to kill cysts of entamoeba histolytic which causes amebic dysentery

Question 12

What do Aminoglycosides do once they’re inside the target cell?

Answer 12

1. Inhibit initiation of protein synthesis
2. Cause misreading of mRNA creating faulty proteins
3. Cause premature termination of protein synthesis

Question 13

Why should you use caution when giving a pregnant lady an Aminoglycoside?

Answer 13

Can accumulate in fetal plasma → neonatal ototoxicity

Question 14

What condition can Aminoglycosides make worse and why?

Answer 14

Myasthenia gravis because in this disease there is an Ab against the nicotinic receptor at the neuromuscular junction (→extreme muscle weakness and amino glycosides can also block this receptor and exacerbate the condition

Question 15

Cockcroft-Gault formula

Answer 15

• Used to calculate creatinine clearance

* Cl = (140-age)xlean weight/(72xserum creatinine)

Question 16

Where do Aminoglycosides distribute and why?

Answer 16

Lean body mass because they are polycations

Question 17

What is the formula to calculate Aminoglycoside does?

Answer 17

Max daily dose x estimated Cl/normal Cl

Question 18

What is the normal Cler for a typical 70kg male?

Answer 18

120-125 ml/min