Lactic acidosis drug-related

MANAGING LACTIC ACIDOSIS. When taking metformin, the patient is at risk for lactic acidosis. The nurse monitors die patient for symptoms of lactic acidosis, which include unexplained hyperventilation, myalgia, malaise, gastrointestinal symptoms, or unusual somnolence If the patient experiences these symptoms, the nurse should contact the primary care provider at once. Elevated blood lactate levels of greater than 5 mmol/L are associated with lactic acidosis and should be reported immediately. Once a patient s diabetes is stabilized on metformin therapy, the adverse GI reactions that often occur at the beginning of such therapy are unlikely to be related to the drug therapy. A later occurrence of GI symptoms is more likely to be related to lactic acidosis or other serious disease. 

Neurologic symptoms Motor weakness has been reported rarely. Most of these cases occurred in the setting of lactic acidosis. The evolution of motor weakness may mimic the clinical presentation of Guillain-Barre syndrome (including respiratory failure). Symptoms may continue or worsen following discontinuation of therapy. Stavudine therapy has been associated with peripheral neuropathy, which can be severe and is dose-related. Peripheral neuropathy has occurred more frequently in patients with advanced HIV disease, a history of neuropathy, or concurrent neurotoxic drug therapy, including didanosine (see Adverse Reactions). 

The principal toxicity of linezolid is hematologic—reversible and generally mild. Thrombocytopenia is the most common manifestation (seen in approximately 3% of treatment courses), particularly when the drug is administered for longer than 2 weeks. Anemia and neutropenia may also occur, most commonly in patients with a predisposition to or underlying bone marrow suppression. Cases of optic and peripheral neuropathy and lactic acidosis have been reported with prolonged courses of linezolid. These side effects are thought to be related to linezolid-induced inhibition of mitochondrial protein synthesis. 

Metformin has a half-life of 1.5-3 hours, is not bound to plasma proteins, is not metabolized, and is excreted by the kidneys as the active compound. As a consequence of metformin s blockade of gluconeogenesis, the drug may impair the hepatic metabolism of lactic acid. In patients with renal insufficiency, biguanides accumulate and thereby increase the risk of lactic acidosis, which appears to be a dose-related complication. 

The lactic acidosis seen with these drugs has ranged from mild and chronic to acute, severe, and fatal [95-106]. The acidosis generally develops after several months of therapy. Patients with NRTl-associated lactic acidosis present with symptoms of nausea, vomiting and abdominal pain. Other features often include elevated liver enzymes, hepatic steatosis, pancreatitis and elevated creatinine kinase with evidence of a myopathy, and liver failure. The lactic acidosis may persist for many weeks despite discontinuation of the NRTl [95-106]. NRTl-related mitochondrial toxicity may also present with rhabdomyolysis and acute kidney failure [110]. Mortality related to NRTl-induced acute lactic acidosis is high, in the range of 50% to 100%, despite drug discontinuation. 

NRTI [82-93]. NRTI-related mitochondrial toxicity may also present with rhabdomyolysis and acute renal failure [%]. Mortality related to NRTl-induced acute lactic acidosis is high, in the range of 50% to 100%, despite drug discontinuation. 

As previously published, multiple further retrospective studies have been performed that demonstrate the good side effect profile with no or minimal drug-related adverse events or early study drug discontinuations with ente-cavir in the treatment of chronic hepatitis B [92-94 ]. Furthermore, several studies [95 96 ] have specifically looked for and not detected any cases of lactic acidosis in their patients on entecavir treatment, while one review article has commented on the lactic acidosis being more attributable to the severity of tire xmderlying hepatic pathology as opposed to the entecavir therapy [97 ]. 

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