Aminoglycosides

Question 1

What is the MOA of aminoglycosides?

Answer 1

1. Rapid bactericidal effect
   Irreversible inhibitors of protein synthesis (target 30S subunit)
2. Concentration-dependent killing
3. Exhibit POST-ANTIBIOTIC effect
   Thus, very effective when given at high doses, with extended dosing intervals

Question 2

What are the 3 mechanisms of resistance?

Answer 2

1. Inactivation by enzymes - phosphorylation, adenylation, acetylation
2. Reduced cell entry - genotypic, phenotypic
3. Mutations - 30s ribosome modified

Question 3

What are the pharmacokinetics?

Answer 3

GIT - poor absorption
IMI - Peak concentrations 30 – 90 minutes
IVI - Peak concentrations 30 – 60 minutes
D - Highly polar
Excluded from most cells: CNS, Eye
(except in cases of INFLAMMATION)
High concentrations -renal cortex (nephrotoxicity)
Inner Ear (ototoxicity)
E - Glomerular filtration

Question 4

How many times is the drug administered?

Answer 4

TDS, once daily for neonates, critically ill neutropenic patients

Question 5

What are some dosing recommendations that need to be considered

Answer 5

Dosing every 24 hours, instead of every 8 hours leads to less time spent in the levels above toxicity

Question 6

What must be considered for the administration of a synergistic effect?

Answer 6

β-lactam or Vancomycin FIRST, THEN Aminoglycoside, SYNERGISM:
MOA
SPECTRUM

Question 7

What is the spectrum of activity?

Answer 7

Mainly G-, aerobic bacilli
E. coli
Proteus
Pseudomonas
Klebsiella pneumoniae
Mycobacterium tuberculosis
Some G+ves (limited)
Staph (endocarditis) (not anaerobes)
Streptococci (veridans)
Enterococcus
+ β-lactam = SYNERGISM

Question 8

What is the efficacy against eskape pathogens?

Answer 8

K - Klebsiella pneumoniae
A – Acinetobacter baumannii
P – Pseudomonas aeruginosa
E – Escherichia coli

Question 9

What are the gaps in the spectrum?

Answer 9

Gram + organisms, Anaerobes

Question 10

What are the adverse effects?

Answer 10

Nephrotoxicity, Neuromuscular blockade, Ototoxicity

Question 11

What are the most nephrotoxic agents?

Answer 11

Neomycin, tobramycin, gentamicin

Question 12

What are some of the ototoxic adverse effects?

Answer 12

Vestibular
ataxia
vertigo
loss of balance

Cochlear
loss oh high frequency hearing
tinnitus
sensation of fullness in ears

Question 13

What increases the risk of aminoglycoside toxicity?

Answer 13

3 days of therapy
Frequent or very high doses
Elderly
Renal dysfunction
Auditory disturbance risk factors

Question 14

Explain the neuromuscular blockade.

Answer 14

Neuromuscular blockade. Due to blocking presynaptic release of Ach. Neomycin does this the most.

Question 15

Other adverse effects?

Answer 15

Headache, Tremor, Lethargy, Hypersensitivity reactions

Question 16

What are some contraindications

Answer 16

Myasthenia gravis
Others:
Pregnancy - not recommended
Lactation – enters breastmilk but not well absorbed
Geriatrics - caution

Question 17

List 4 drug interactions?

Answer 17

Ototoxic drugs, Nephrotoxic drugs, Neuromuscular blockers, General anaesthetics