Anti-tubercular drugs

Anti-tubercular drugs


Antitubercular drugs


       Pharmacology of individual drugs

At the end of this lecture, the student will be able to:

       Describe the mechanism of action and pharmacokinetics of First line and second line anti-TB drugs

       Discuss the adverse effects and drug interactions of anti-TB drugs

       Explain the DOTS therapy based on WHO guidelines

Anti-tubercular Agents

       Tuberculosis is a chronic granulomatous disease

       In developing countries it is a major health problem

       30% of world population is infected with M. tuberculosis infection

       In India > 2 million people develop active disease every year & half million die.

       Anti-tubercular drugs used in chemotherapy of tuberculosis, a disease caused by Mycobacterium tuberculosis

       Many drugs were developed to treat tuberculosis and they are often used in combinations to reduce the emergence of resistant strains of the mycobacterium

       Combination chemotherapy is also used in the treatment of leprosy, caused by Mycobacterium leprae


                First-line (High efficacy, low toxicity)






                Second-line (Low efficacy, high toxicity)







      Para amino salicylic Acid

Isoniazid (Isonicotinic Acid Hydrazid)

        Isoniazid is an effective anti-tubercular drug and is essential component of all anti tubercular regimens

       It is more potent among the anti-tubercular drugs, but it is not used alone in treatment of active tuberculosis

       It acts on extracellular as well as on intercellular tubercule bacilli present within macrophages

Mode of Action

       Acts only on mycobacteria

       Interferes with mycolic acid synthesis (unique to mycobacterial cell wall)

       Passes freely to mammalian cell wall

       Effective for intracellular organism

       Bacteriostatic – to resting organism

       Bactericidal – to multiplying organism


       Well absorbed from GIT

       Fatty food & aluminium-containing antacids may reduce absorption

       CSF penetration: 20% of plasma concentration with non-inflamed meninges 

       Penetrate well into caseous material

       Excretion – urine

       Plasma half-life 3 hrs

Adverse Effects


      Elderly, slow acetylators more prone


      Prevented by concurrent pyridoxine

       Rashes, acne

       Heamatological – haemolytic anaemia in G6PD deficiency

Drug Interactions

       Absorption of Isoniazid is impaired if taken with food consisting carbohydrates or with aluminium-containing antacids

       It inhibits the metabolism of phenytoin, carbamazepine, diazepam and warfarin and raised their blood levels

       Para amino salicylic acid inhibits its metabolism and increases its metabolism


       Rifampicin is semisynthetic derivative of refamycin B, obtained from Streptomyces mediterannei

       It is one of the most active anti tubercular drugs

       It is active against many other Gram-positive and Gram-negative bacteria

Mechanism of Action

       Rifampicin acts by inhibiting DNA- dependent RNA polymerase thus inhibiting RNA synthesis by suppressing the initiation step in prokaryotic but not in eukaryotic cells

       It also enters phagocytic cells and kill intercellular microorganism including tubercule bacilli

       It is the only drug which acts on the persisters


       It is well absorbed orally and is widely distributed in the tissues and body fluids

       It gives an orange tinge to saliva, sputum, tears and sweat

       The drug is taken up by liver and undergoes enterohepatic cycling

       The metabolite retains antibacterial activity but less absorbed from the GIT tract

       Mainly Excreted in bile and also in urine

Adverse Effects

       Unwanted effects are infrequent and include skin eruptions, fever and GIT disturbances

       The drug should be used carefully in patients with hepatic failure as it may lead to jaundice

Drug Interactions

       Rifampicin is an inducer of cytochrome P-450 enzymes and decreases the half-life of drugs such as warfarin, glucocorticoids, antidiabetic, oral-contraceptives leading to their failure

Anti-TB Therapy

       Multiple drugs are used to reduce the emergence of resistance

       Given as combination tablets

       Taken 30 min before the breakfast as absorption of rifampicin is influenced by food

       For pulmonary TB – 6 months treatment

       For renal, bone and CNS infection – longer treatment


       Isoniazid – bactericidal to rapidly dividing bacteria

       Rifampicin - kill intracellular bacteria

       Ethambutol – bacteriostatic against multiplying bacteria

       Pyrazinamide - kill dormant mycobacteria

       Adverse effects:

ü  INH- Hepatotoxicity and Polyneuropathy

ü  Rifampicin- inducer of cytochrome P-450 enzymes and decreases the half-life of drugs such as warfarin, glucocorticoids, antidiabetic, oral-contraceptives

ü  Pyrazinamide- GI disturbances, Hepatotoxicity,  gout

ü  Streptomycin- Ototoxicity, vestibular toxicity, nephrotoxicity



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