Oxazolidinones

Question 1

Mechanism of action of oxazolidinones

Answer 1

Inhibits protein synthesis

It acts by potent interaction with 50S ribosomal subunit. This interaction prevents the formation of the 70S initiation complex.

Linezolid interacts specifically with 23S rRNA.

Question 2

Ribosome formation

What portion of the ribosome does linezolid interact with?

Answer 2

In the initiation step of bacterial translation, the 50S subunit associates with fMet-tRNA and a complex composed of the 30S ribosomal subunit and mRNA to form the functional 70S initiation complex.

Linezolid interacts with the 50S subunit with micromolar affinity (and it has no affinity to the 30S subunit).

Question 3

Therapeutic uses of linezolid

Answer 3

1. Vancomycin-resistant Enterococcus faecium
2. Nosocomial pneumonia caused by methacillin-–resistant strains of Staphylococcus aureus
3. Skin infections caused by methicillin–resistant strains of Staphylococcus aureus

Question 4

Advantage of linezolid

Answer 4

It has excellent oral bioavialability

Question 5

To reduce the development of drug-resistant bacteria and maintain the effectiveness of linezolid, it should be used …

Answer 5

only to treat or prevent infections that are proven or strongly suspected to be caused by multiply drug-resistant Gram-(+) bacteria

Question 6

Resistance to linezolid

Answer 6

Target site modification is virtually the only mechanism thus far

Resistance mutations identified in various species are associated with G to U substitution in the peptidyl transferase center of 23S rRNA at position 2576 and result in reduced affinity of linezolid to the 50S subunit

Question 7

Side effects of linezolid

Answer 7

N/V/D

headache, tongue discoloration and oral Monilia infection

More serious side effects included thrombocytopenia, GI bleeding and anemia

Question 8

Monilia

Answer 8

Old term for Candida albicans

e.g. oral monilia infection is thrush

Question 9

Long-term treatment resulted in…

Answer 9

Fully reversible myelosuppression

Neuropathy (detected in some cases)

Question 10

Pharmacokinetics of linezolid

Answer 10

Linezolid is 100% bioavailable after oral administration and has a half-life to 4-6 hours. It is administered either orally or intravenously.

Question 11

Linezolid is neither an inducer nor an inhibitor of …

Answer 11

cytochrome P450

Therefore, no CYP450- mediated drug interactions are expected

Question 12

Linezolid Drug Interactions

• Linezolid is a reversible, nonselective inhibitor of …
• What response has been observed when linezolid is administered to normotensive subjects?
• patients taking linezolid should not consume …

Answer 12

monoamine oxidase
— therefore, it has the potential for interaction with adrenergic and serotonergic agents

a reversible potentiation of pressor response to pseudoephedrine or phenylpropanolamine

large quantities of foods or beverages that are rich in tyramine in order to avoid a significant pressor response