Anti Tuberculosis Drugs
Indications of Antituberculosis Drugs
Tuberculosis is managed by the following drugs usually in combination to prevent mycobacterium resistance and toxicity.
Rifampicin symbolized by R .
Isoniazid symbolized by H.
Pyrazinamide symbolized by Z.
Ethambutol symbolized by E.
Streptomycin symbolized by S .
Tuberculosis is usually managed in two phases, initial phases and continuous phase.
The initial phase; during this phase combination drugs are continued for 2 months. Drugs used in initial phase are rifampicin, isoniazid, pyrazinamide and ethambutol. These drugs should be continued until full susceptibility is confirmed, even if this is for longer than 2 months .
Continuation phase; after the initial phase, treatment is continued for a further 4 months with isoniazid and rifampicin (preferably given as a combination preparation). Longer treatment is necessary for meningitis, direct spinal cord involvement, and for resistant organisms which may also require modification of the regimen .
Other drugs indicated for management of tuberculosis as second line include cycloserine, ethionamide and streptomycin.
STEP 3: Contraindications of Antituberculosis Drugs:
Rifampicin is contraindicated to patient with jaundice.
Isoniazid is contraindicated to patient with drug induced liver disease .
Pyrazinamide is contraindicated to patient with Hepatic disorders .Patients or their careers should be told how to recognize signs of liver disorder, and advised to discontinue treatment and seek immediate medical attention if symptoms such as persistent nausea, vomiting, malaise or jaundice develope.
Ethambutol is contraindicated in optic neuritis and poor vision.
Streptomycin is contraindicated to patient with mythenia gravis.
Cycloserine is contraindicated to patient with epilepsy, depression, severe anxiety, psychotic states, alcohol dependence and acute porphyria.
STEP 4: Dose, Dosage and Course of Antituberculosis Drugs:
Rifampicin Is usually given 600 mg/daily (10 mg/kg/d) orally, must be administered with isoniazid or other antituberculosis drugs to patients with active tuberculosis to prevent emergence of drug-resistant mycobacteria.
Rifampin 600 mg daily or twice weekly for 6 months also is effective in combination with other agents in some atypical mycobacterial infections and in leprosy.
Isoniazid Usual dosage is 5 mg/kg/d; a typical adult dose is 300 mg given once daily. Up to 10 mg/kg/d may be used for serious infections or if malabsorption is a problem A 15 mg/kg dose, or 900 mg, may be used in a twice-weekly dosing regimen in combination with a second antituberculosis agent (e.g., rifampin 600 mg).
Pyridoxine, 25-50 mg/d, is recommended for those with conditions predisposing to neuropathy, an adverse effect of isoniazid.
Isoniazid is usually given by mouth but can be given parenterally in the same dosage.
Pyrazinamide Should be used at a dose of 40-50 mg/kg is used for thrice-weekly or twice-weekly treatment regimens. Pyrazinamide is an important front-line drug used in conjunction with isoniazid and rifampin in short-course (ie, 6-month) regimens as a "sterilizing" agent active against residual intracellular organisms that may cause relapse.
Ethambutol As hydrochloride salt is given at 15-25 mg/kg, is usually given as a single daily dose in combination with isoniazid or rifampin. The higher dose is recommended for treatment of tuberculous meningitis. The dose of ethambutol is 50 mg/kg when a twice-weekly dosing schedule is used. Streptomycin The usual dosage is 15 mg/kg/d intramuscularly or intravenously daily for adults (20-40 mg/kg/d, not to exceed 1-1.5 g for children) for several weeks, followed by 1-1.5 g two or three times weekly for several months.
STEP 5: Side Effects and Adverse Effects of Antituberculosis:
Side effects and adverse effects of antituberculosis drugs include:
Rifampicin Occasional adverse effects include rashes, thrombocytopenia, and nephritis. It may cause cholestatic jaundice and occasionally hepatitis.Rifampin commonly causes light-chain proteinuria.
Isoniazid side effects are dose related They occur in high dose and may include nausea, vomiting, constipation, dry mouth; peripheral neuritis with high doses (pyridoxine prophylaxis, see notes above), optic neuritis, convulsions, psychotic episodes and vertigo.
Pyrazinamide, Major adverse effects of pyrazinamide include; hepatotoxicity, nausea, vomiting, drug fever, and hyperuricemia Hyperuricemia may provoke acute gouty arthritis
Ethambutol; the most common serious adverse event is retro bulbar neuritis, resulting in loss of visual acuity and red-green color blindness.
Streptomycin is ototoxic and nephrotoxic Vertigo and hearing loss are the most common side effects and may be permanent. Toxicity is dose-related, and the risk is increased in the elderly Toxicity can be reduced by limiting therapy to no more than 6 months whenever possible.
STEP 6: Interactions and Precautions of Antituberculosis
Interactions: There is no serious interaction between ant tuberculosis drugs and other drugs except that rifampicin reduces plasma concentration of digoxin.
Absorption of isoniazid is reduced by antacids, Hepatotoxic of isoniazid is potentiated by general anaesthesia and its CNS toxicity is increased by cycloserine
Pyrazinamide antagonizes effect of probenecid Precautions:
Rifampicin should be given with care in hepatic impairment, renal impairment pregnancy and breast-feeding.
Isoniazid should be given with care in hepatic impairment, renal impairment, slow acetylator status, epilepsy and history of psychosis.
Pyrazinamide should be given with care in pregnancy, hepatic impairment, diabetes and gout.
Ethambutol should be given with care in renal impairment, elderly and pregnancy.
Streptomycin should be given with care in pregnancy, renal impairment,neonates, infants and elderly.
STEP 7: Key points:
Ant tuberculosis drugs should be given in combination to prevent microbial resistance and minimize side effects.
Management of TB is done in two phases, initial phase and continuous phase.
Ant tuberculosis drugs should be given on DOT especially during first phase STEP 7:References:
Robert L. Talbert, Gary C. Yee, Gary R. Matzke, Barbara G. Wells, L. Michael. 2014. Pharmacotherapy: a pathophysiologic approach (9th ed.).
New York, McGraw-Hill Education Ministry Of Health and Social Welfare. 2013.
Standard Treatment Guidelines & National Essential Medicines List Tanzania Mainland (4th ed.). Dar es Sally salaam, Tanzania government printers . S.R, Jeanne C.S. 2000.
Introductory Clinical Pharmacology (6th ed) New York, Lippincott Williams and Wilkins School of Pharmaceutical sciences. 2011.
Tanzania Pharmaceutical Handbook (2nd ed.). Dar es Salaam, ARDHI University press.
The Royal Pharmaceutical Society of Great Britain. 2007.
Martindale, the Extra Pharmacopoeia (5TH ed). London, pharmaceutical press.
The Royal Pharmaceutical Society of Great Britain. 2009.
British National Formulary (59th ed). London, BMJ Group and RPS Publishing.
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