Oxazolidinones

Question 1

What is the mechanism of action for linezolid?

Answer 1

MOSTLY. Bacteriostatic. Bactericidal against Strep species. Time-dependent

Inhibits protein synthesis by:
Binding to 23S ribosomal RNA of the 50S subunit (unique binding site).
Prevents formation of the 70s initiation complex that initiates protein synthesis

Question 2

What is spectrum of activity?

Answer 2

PRSP, MRSA, VRSA,VREF.

Question 3

What are some of the clinical uses?

Answer 3

Skin and soft tissue infections
Efficacy ≈ vancomycin
S aureus
Respiratory Tract Infections
Nosocomial pneumonia (≥ vancomycin)
Community-acquired pneumonia
VREF
Great efficacy against various infections
Drug-Resistant TB
Part of combination therapies

Question 4

When is linezolid used mostly?

Answer 4

RESERVED for treatment of infections caused by multiple-drug-resistant strains or when other agents ineffective

Question 5

What are the pharmacokinetics?

Answer 5

Bioavailability = 100%
Unaffected by food
Vd = 40 – 50L
Penetrates bone, fat + muscles well
t1/2 = 5 – 7 hrs
Dose: 600mg BD
M - oxidative
No liver enzyme inhibition or induction
E - 65% Non-renal mechanisms

Question 6

What are some adverse effects?

Answer 6

GIT Effects
N/V/Diarrhoea
CNS Effects
Headache, dizziness
Reversible Bone Marrow Suppression (Thrombocytopenia)
- Anaemia
Reversible Optic Neuropathy
Irreversible Peripheral Neuropathy
Lactic Acidosis
Serotonin Syndrome (Weak MAOI)

Question 7

What are some drug interactions?

Answer 7

NO CYP450 interactions, Tramadol, SSRIs, MAOIs, TCADs etc, Vasopressor drugs, Sympathomimetics, Dopaminergic Drugs

Question 8

What are some precautions?

Answer 8

Bone Marrow Suppression
Risk of bleeding, thrombocytopenia
Disorders of platelet function
If > 2 weeks, monitor full blood count
Lactation
May be excreted in milk
Exercise caution
Pregnancy
Use only if potential benefits justifies the risk to the fetus