A second line drug for tuberculosis is either less effective than the first line drug or has an associated toxicity that makes second choice for use in tuberculosis patients.
Second class drugs are used when the patient either does not respond to first line or does not tolerate them and substantiating the treatment is necessary.
Following are second-line drugs used for the treatment of tuberculosis.
- Thioacetazone (T)
- P-aminosalicylic acid (PAS or P).
- Thioamides – Ethionamide, prothionamide
- Cycloserine
- Polypeptides- capreomycin, viomycin, enviomycin
- Aminoglycosides: e.g., amikacin (AMK), kanamycin (KM)
- Fluoroquinolones-Ciprofloxacin (CIP), levofloxacin, moxifloxacin (MXF), Ofloxacilin
Commonly used drugs are discussed below-
Thiacetazone
Thioacetazone is a bacteriostatic drug [Inhibits the growth of bacteria but does not kill existing]. It has poor cerebrospinal fluid penetration. Its mechanism of action is not clear. The dose of the drug is 150 mg per oral. It may cause gastrointenstinal disturbances, skin reactions including exfoliative dermatitis,hepatotoxicity, myelosuppression [suppression of bone marrow].
It is not used in AIDS patients. Due to its toxic profile the use of Thioacetazone is reducing and it is used in cases where other choices have exhausted.
PAS
P-aminosalicylic acid is again a bacteriostatic drug with poor CSF penetration. It acts by inhibiting folate synthesis and interferes with incorporation of p-amino benzoic acid. The dose is 150 mg/kg per oral in divided doses with meals. Maximum allowed dose is 12 gm.
Side effects like gastrointenstinal disturbances, hypersensitivity like rash, feve malaise, arthralgia, and changes in blood count like leucopenia, agranulocytosis, eosinophilia, lymphocytosis, atypical mononucleosis, thrombocytopenia, hemolytic anemia. This drug is active against mycobacterium tuberculosis only.
Ethionamide
It is a bacteriostatic drug and has a good CSF penetration. It acts as nicotinamide analog and possibly inhibits incorporation of cysteine and methionine proteins. It is recommended in doses of 15-20 mg/kg orally in divided doses with meals. The maximum dose should not increase more than one gram.
The known side effects are gastrointenstinal disturbances, neurotoxicity, visual disturbances, olfactiry distubances, peripheral neuropathy, convulsions, hepatotoxicity, hypersensitivity reactions, alopecia and gynecomastia.
Pyridoxine supplements can reduce the toxicity. Liver functions must be monitored during therapy.
If used alone, resistance develops very soon. It also shows cross resistance with thioacetazone
Cycloserine
A bacteriostatic drug with very good CSF penetration. It inhibits cell wall synthesis. Dose is 10-20 mg/kg per oral in 2 divided doses. Maximum dose is 500 mg twice daily. Headcahe, dizziness, vertigo, drowsiness, tremors, convulsions, depresion, psychosis, abnormal liver function, megaloblastic anemia, rashes are known side effects.
Hematological, renal and hepatic functions should be monitored.
Capreomycin
The drug is given in intramuscular injection form. It is a bacteriocidal drug with poor CSF penetration. The dose is 15-30mg/kg . Maximum dose is 1 gram. Induration at the site of injection, Ear and kidney toxicity, fever, rashes, eosinophilia are known side effects. High doses may cause neuromuscular blockade. Resistance to this drug develops after short use. It also shows cross resistance with aminoglycosides.
Amikacin, Kanamicin
These are bacteriocidal drugs that belong to aminoglycocide class and have poor CSF penetration. Dose is 15mg/kg intramuscular injection form.
Ootoxicity, nephrotoxicity, pesudomembranous colitis and neuromucular blockade are common side effects.
Fluoroquinolones should not be used in children.
Newer drugs like macrolides (e.g. Azithromycin; Clarithromycin), rifamycins, (e.g. Rifabutin and the long-acting Rifapentine) and nitroimidazoles (e.g. PA-824) are being evaluated fro their efficacy.
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