ion of the blood. methemoglobin levels may continue to rise; therefore, immediate treatment is required to avert more serious central nervous system and cardiovascular adverse effects, including seizures, coma, arrhythmias, and death. discontinue [the use of this product] and any other oxidizing agents. depending on the severity of the symptoms, patients may respond to supportive care, i.e., oxygen therapy, hydration. more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.

ed during pregnancy only if the potential benefit justifies the potential risk to the fetus. drugs of this class should not be used extensively on pregnant patients, in large amounts, or for prolonged periods of time.

dly after intratracheal administration. lidocaine is also well-absorbed from the gastrointestinal tract, but little intact drug appears in the circulation because of biotransformation in the liver. lidocaine is metabolized rapidly by the liver, and metabolites and unchanged drug are excreted by the kidneys. biotransformation includes oxidative n-dealkylation, ring hydroxylation, cleavage of the amide linkage, and conjugation. n-dealkylation, a major pathway of biotransformation, yields the metabolites monoethylglycinexylidide and glycinexylidide. the pharmacological/toxicological actions of these metabolites are, similar to but less potent than, those of lidocaine. approximately 90% of lidocaine administered is excreted in the form of various metabolites, and less than 10% is excreted unchanged. the primary metabolite in urine is a conjugate of 4-hydroxy-2, 6-dimethylaniline. the plasma binding of lidocaine is dependent on drug concentration, and the fraction bound decreases with increasing concentration. at concentrations of 1 to 4 g of free base per ml, 60 to 80 percent of lidocaine is protein bound. binding is also dependent on the plasma concentration of the alpha-1-acid glycoprotein. lidocaine crosses the blood-brain and placental barriers, presumably by passive diffusion. studies of lidocaine metabolism following intravenous bolus injections have shown that the elimination half-life of this agent is typically 1.5 to 2 hours. because of the rapid rate at which lidocaine is metabolized, any condition that affects liver function may alter lidocaine kinetics. the half-life may be prolonged two-fold or more in patients with liver dysfunction. renal dysfunction does not affect lidocaine kinetics but may increase the accumulation of metabolites. factors such as acidosis and the use of cns stimulants and depressants affect the cns levels of lidocaine required to produce overt systemic effects. objective adverse manifestations become increasingly apparent with increasing venous plasma levels above 6 g free base per ml. in the rhesus monkey arterial blood levels of 18-21 g/ml have been shown to be threshold for convulsive activity. the extent of percutaneous absorption of topical corticosteroids is determined by many factors including the vehicle, the integrity of the epidermal barrier, and the use of occlusive dressings. topical corticosteroids can be absorbed from normal intact skin. inflammation and/or other disease processes in the skin increase percutaneous absorption. occlusive dressings substantially increase the percutaneous absorption of topical corticosteroids. thus, occlusive dressings may be a valuable therapeutic adjunct for treatment of resistant dermatoses. once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. corticosteroids are bound to plasma protein in varying degrees. corticosteroids are metabolized primarily in the liver and are then excreted by the kidneys. some of the topical corticosteroids and their metabolites are also excreted into the bile.

ose of lidocaine. approximately 90% of lidocaine administered is excreted in the form of various metabolites, and less than 10% is excreted unchanged. the primary metabolite in urine is a conjugate of 4-hydroxy-2, 6-dimethylaniline. the plasma binding of lidocaine is dependent on drug concentration, and the fraction bound decreases with increasing concentration. at concentrations of 1 to 4 g of free base per ml, 60 to 80 percent of lidocaine is protein bound. binding is also dependent on the plasma concentration of the alpha-1-acid glycoprotein. lidocaine crosses the blood-brain and placental barriers, presumably by passive diffusion. studies of lidocaine metabolism following intravenous bolus injections have shown that the elimination half-life of this agent is typically 1.5 to 2 hours. because of the rapid rate at which lidocaine is metabolized, any condition that affects liver function may alter lidocaine kinetics. the half-life may be prolonged two-fold or more in patients with liver dysfunction. renal dysfunction does not affect lidocaine kinetics but may increase the accumulation of metabolites. factors such as acidosis and the use of cns stimulants and depressants affect the cns levels of lidocaine required to produce overt systemic effects. objective adverse manifestations become increasingly apparent with increasing venous plasma levels above 6 g free base per ml. in the rhesus monkey arterial blood levels of 18-21 g/ml have been shown to be threshold for convulsive activity. the extent of percutaneous absorption of topical corticosteroids is determined by many factors including the vehicle, the integrity of the epidermal barrier, and the use of occlusive dressings. topical corticosteroids can be absorbed from normal intact skin. inflammation and/or other disease processes in the skin increase percutaneous absorption. occlusive dressings substantially increase the percutaneous absorption of topical corticosteroids. thus, occlusive dressings may be a valuable therapeutic adjunct for treatment of resistant dermatoses. once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. corticosteroids are bound to plasma protein in varying degrees. corticosteroids are metabolized primarily in the liver and are then excreted by the kidneys. some of the topical corticosteroids and their metabolites are also excreted into the bile.