Although some participants of early trials did experience thrombocytopenia, it was found to be reversible and did not occur significantly more frequently than in controls (participants not taking linezolid). There have also been postmarketing reports of seizures, and, as of 2009, a single case each of Bells palsy (paralysis of the facial nerve) and kidney toxicity. Evidence of protein synthesis inhibition in mammalian cells by linezolid has been published. Interactions
Linezolid is a weak, non-selective, reversible monoamine oxidase inhibitor (MAOI), and should not be used concomitantly with other MAOIs, large amounts of tyramine-rich foods (such as pork, aged cheeses, alcoholic beverages, or smoked and pickled foods), or serotonergic drugs. There have been postmarketing reports of serotonin syndrome when linezolid was given with or soon after the discontinuation of serotonergic drugs, particularly selective serotonin reuptake inhibitors (SSRIs) such as paroxetine and sertraline. It may also enhance the blood pressure-increasing effects of sympathomimetic drugs such as pseudoephedrine or phenylpropanolamine. It should also not be given in combination with pethidine (meperidine) under any circumstance due to the risk of serotonin syndrome. Linezolid does not inhibit or induce the cytochrome P450 (CYP) system, which is responsible for the metabolism of many commonly used drugs, and therefore does not have any CYP-related interactions. Pharmacology
Pharmacodynamics
Linezolid, like other oxazolidinones, is a bacterial protein synthesis inhibitor and a weak, non-selective, reversible monoamine oxidase inhibitor. As a protein synthesis inhibitor, linezolid stops the growth and reproduction of bacteria by disrupting translation of messenger RNA (mRNA) into proteins in bacterial ribosomes.
The lactate is carried by the bloodstream to other tissues where it is converted at the expense of ATP back to pyruvate by the "B" isoform of LDH (LDHB). Firstly there is gluconeogenesis in the liver (as well as the kidney and some other tissues), where pyruvate is converted into glucose; this is known as the Cori cycle. In addition, lactate moved to other tissues enters the citric acid cycle and eventually oxidative phosphorylation, a process that yields ATP.Elevations in lactate are either a consequence of increased production or of decreased metabolism. With regards to metabolism, this predominantly takes place in the liver (70%), which explains that lactate levels may be elevated in the setting of liver disease.In "type A" lactic acidosis, the production of lactate is attributable to insufficient oxygen for aerobic metabolism. If there is no oxygen available for the parts of the glucose metabolism that require oxygen (citric acid cycle and oxidative phosphorylation), excess pyruvate will be converted in excess lactate. In "type B" lactic acidosis the lactate accumulates because there is a mismatch between glycolysis activity and the remainder of glucose metabolism. Examples are situations where the sympathetic nervous system is highly active (e.g. severe asthma). There is controversy as to whether elevated lactate in acute illness can be attributed to tissue hypoxia; there is limited empirical support for this theoretical notion. Diagnosis
Acid-base disturbances such as lactic acidosis are typically first assessed using arterial blood gas tests. Testing of venous blood is also available as an alternative as they are effectively interchangeable.