Capreomycin is nephrotoxic and ototoxic.Tinnitus,deafness,and vestibular disturbances occur. The injection causes significant local pain,and sterile abscesses may occur. Dosing of capreomycin is the same as that of streptomycin.Toxicity is reduced if 1 g is given two or three times weekly after an initial response has been achieved with a daily dosing schedule Cycloserine Cycloserine is an inhibitor of cell wall synthesis and is discussed in Chapter 43.Concentrations of 15-20 mcg/mL inhibit many strains of M tuberculosis.The dosage of cycloserine in tuberculosis is 0.5-1 g/d in two divided doses.Cycloserine is cleared renally,and the dose should be reduced by half if creatinine clearance is less than 50 mL/min. The most serious toxic effects are peripheral neuropathy and central nervous system dysfunction, including depression and psychotic reactions.Pyridoxine 150 mg/d should be given with cycloserine because this ameliorates neurologic toxicity.Adverse effects,which are most common during the first 2 weeks of therapy,occur in 25%or more of patients,especially at higher doses. Side effects can be minimized by monitoring peak serum concentrations.The peak concentration is reached 2-4 hours after dosing.The recommended range of peak concentrations is 20-40 mcg/mL Aminosalicylic Acid (PAS) Aminosalicylic acid is a folate synthesis antagonist that is active almost exclusively against M tuberculosis.It is structurally similar to p-aminobenzoic aid (PABA)and to the sulfonamides (see Chapter 46) Tubercle bacilli are usually inhibited in vitro by aminosalicylic acid,1-5 mcg/mL.Aminosalicylic acid is readily absorbed from the gastrointestinal tract.Serum levels are 50 mcg/mL or more after a 4-g oral dose.The dosage is 8-12 g/d orally for adults and 300 mg/kg/d for children.The drug is widely distributed in tissues and body fluids except the cerebrospinal fluid.Aminosalicylic acid is rapidly excreted in the urine,in part as active aminosalicylic acid and in part as the acetylated compound and other metabolic products.Very high concentrations of aminosalicylic acid are reached in the urine,which can result in crystalluria. Aminosalicylic acid is used infrequently now because other oral drugs are better tolerated. Gastrointestinal symptoms are common and may be diminished by giving the drug with meals and with antacids.Peptic ulceration and hemorrhage may occur.Hypersensitivity reactions manifested by fever,joint pains,skin rashes,hepatosplenomegaly,hepatitis,adenopathy,and granulocytopenia often occur after 3-8 weeks of aminosalicylic acid therapy,making it necessary to stop aminosalicylic acid administration temporarily or permanently Kanamycin AmikacinCapreomycin is nephrotoxic and ototoxic. Tinnitus, deafness, and vestibular disturbances occur. The injection causes significant local pain, and sterile abscesses may occur. Dosing of capreomycin is the same as that of streptomycin. Toxicity is reduced if 1 g is given two or three times weekly after an initial response has been achieved with a daily dosing schedule. Cycloserine Cycloserine is an inhibitor of cell wall synthesis and is discussed in Chapter 43. Concentrations of 15-20 mcg/mL inhibit many strains of M tuberculosis. The dosage of cycloserine in tuberculosis is 0.5-1 g/d in two divided doses. Cycloserine is cleared renally, and the dose should be reduced by half if creatinine clearance is less than 50 mL/min. The most serious toxic effects are peripheral neuropathy and central nervous system dysfunction, including depression and psychotic reactions. Pyridoxine 150 mg/d should be given with cycloserine because this ameliorates neurologic toxicity. Adverse effects, which are most common during the first 2 weeks of therapy, occur in 25% or more of patients, especially at higher doses. Side effects can be minimized by monitoring peak serum concentrations. The peak concentration is reached 2-4 hours after dosing. The recommended range of peak concentrations is 20-40 mcg/mL. Aminosalicylic Acid (PAS) Aminosalicylic acid is a folate synthesis antagonist that is active almost exclusively against M tuberculosis. It is structurally similar to p-aminobenzoic aid (PABA) and to the sulfonamides (see Chapter 46). Tubercle bacilli are usually inhibited in vitro by aminosalicylic acid, 1-5 mcg/mL. Aminosalicylic acid is readily absorbed from the gastrointestinal tract. Serum levels are 50 mcg/mL or more after a 4-g oral dose. The dosage is 8-12 g/d orally for adults and 300 mg/kg/d for children. The drug is widely distributed in tissues and body fluids except the cerebrospinal fluid. Aminosalicylic acid is rapidly excreted in the urine, in part as active aminosalicylic acid and in part as the acetylated compound and other metabolic products. Very high concentrations of aminosalicylic acid are reached in the urine, which can result in crystalluria. Aminosalicylic acid is used infrequently now because other oral drugs are better tolerated. Gastrointestinal symptoms are common and may be diminished by giving the drug with meals and with antacids. Peptic ulceration and hemorrhage may occur. Hypersensitivity reactions manifested by fever, joint pains, skin rashes, hepatosplenomegaly, hepatitis, adenopathy, and granulocytopenia often occur after 3-8 weeks of aminosalicylic acid therapy, making it necessary to stop aminosalicylic acid administration temporarily or permanently. Kanamycin  Amikacin