Walters - Aminoglycosides

Question 1

what is the structure of an aminoglycoside?

Answer 1

amino sugars attached to glycosidic links to an aminocyclitol ring - polycations = very polar (usually given IV)

Question 2

what is the main mechanism for aminoglycosides?

Answer 2

enter periplasmic space of G - bacteria through porin channels and pass through inner membrane by flowing down their electrochemical gradient

Question 3

what are the 3 things that aminoglycosides do once inside a cell?

Answer 3

1. inhibit initiation of protein synthesis
2. cause mis-reading of mRNA and creating faulty proteins = pores
3. premature termination of protein synthesis by breaking up polysomes into non-functional monosomes

Question 4

are aminoglycosides static or cidal?

Answer 4

cidal - even though they inhibit protein synthesis

Question 5

are aminoglycosides effective against anaerobes? and why?

Answer 5

no - they flow down the electrochemical gradient created by electron transport chain (cell respiration)

Question 6

what are aminoglycosides mainly used against?

Answer 6

mostly gram - and used with beta-lactams for synergism and gram + coverage

Question 7

what is the mechanism of synergism with beta-lactams?

Answer 7

by inhibiting cell wall synthesis, B-lactams facilitate penetration of aminoglycosides

Question 8

where do aminoglycosides attain their highest levels?

Answer 8

renal cortex - nephrotoxicity (reversible) and endolymph of inner ear - ototoxicity (irreversible)

Question 9

what are some side effects of aminoglycosides?

Answer 9

• degeneration of auditory nerve (permeant hearing loss), tinnitus, high-frequency hearing loss, vertigo, ataxia, loss of balance, and they can accumulate in fetal placenta = neonatal ototoxicity
• Nephrotoxicity (reversible)

Question 10

what is Gentamicin used for?

Answer 10

topical cream/ointment for burns, wounds and prevent catheter infections, also ophthalmic for topical infections

Question 11

what is Tobramycin used for?

Answer 11

generally interchangeable with Gentamicin, possibly less otoxic than Gentamicin

Question 12

what is Amikacin used for?

Answer 12

it is enzyme resistant - for nosocomial infections that resist Gentamicin and Tobramycin

Question 13

what is Neomycin used for?

Answer 13

Oral - to prep for bowel surgery (also topical anti-infectant)

Question 14

what is Paromomycin used for?

Answer 14

Oral - kills cysts of Entamoeba histolytica which cause amebic dysentery

Question 15

how would you estimate a patients creatinine clearance for calculating a dose?

Answer 15

creatinine clearance is in (ml/min) = (140 - age) x (lean wt in kg) divided by 72 x serum creatinine (mg/dL)

Question 16

what is a rare side effect with aminoglycosides?

Answer 16

neuromuscular block leading to respiratory paralysis during anesthesia when also using a neuromuscular blocker.

Question 17

how does an aminoglycoside cause a neuromuscular block?

Answer 17

they block Ca2+ uptake into cholinergic nerve terminals thus decreasing ACh release (muscle contraction), they also block postsynaptic cholinergic receptors

Question 18

what are 2 possible treatments for the neuromuscular block side effect?

Answer 18

use IV Ca2+ alternative or Neostigmine (cholinesterase inhibitor - inhibits ACh metabolism and increase ACh - stimulating respiratory muscles)

Question 19

what condition should you avoid using Aminoglycosides with? and why?

Answer 19

myasthenia gravis - they produce an Ab against the nicotinic receptors and these drugs with exacerbate the condition