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32.tuberculosis and leprosy

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32.tuberculosis and leprosy

  1. 1. ANTITUBERCULAR DRUGS
  2. 2. • Tuberculosis is a chronic granulomatous disease caused by Mycobacterium tuberculosis • A major health problem in developing countries
  3. 3. Aims of treatment • To kill the dividing bacilli & to destroy the persisters in order to prevent relapse and ensure complete cure  To prevent development of drug resistance.  To decrease transmission to others.
  4. 4. Drugs are combined to: • Delay the development of resistance • Reduce toxicity • Shorten the course of treatment Duration of therapy: Depends on 1.Site of disease, 2.Bacillary load, 3.Severity of disease, 4.History of treatment and resistance.
  5. 5. Classification 1. First line antitubercular drugs (standard drugs) • Isoniazid (H) • Rifampicin (R) • Pyrazinamide (Z) • Ethambutol (E) • Streptomycin (S)
  6. 6. 2. Second line antitubercular drugs (Reserve drugs) • Amikacin • Para - aminosalicylic acid • Kanamycin • Cycloserine • Ethionamide • Thiacetazone • Ciprofloxacin, moxifloxacin, gatifloxacin • Clarithromycin, azithromycin • Rifabutin, rifapentine Newer agents
  7. 7. First line antitubercular drugs (standard drugs)
  8. 8. ISONIAZID (Isonicotinic acid hydrazide, INH) • Mechanism: inhibits the biosynthesis of mycolic acids, which are essential constituents of the mycobacterial cell wall Adverse Reactions: • Hepatitis - loss of appetite, nausea, vomiting, jaundice, and right upper quadrant pain • Peripheral neuropathy (deficiency of pyridoxine ) • Fever, skin rashes , arthralgia, GI disturbances • Psychosis, optic neuritis and rarely convulsions
  9. 9. RIFAMPIN • Mechanism: inhibits bacterial DNA-dependent RNA polymerase inhibits RNA synthesis
  10. 10. Adverse effects • Hepatitis • Flu-like syndrome – fever, chills, headache, muscle & joint pain • GI disturbances • Skin rashes, itching, & flushing • Orange-red discoloration of body fluid secretions such as urine, tears, saliva, sweat, sputum etc - patient to be informed
  11. 11. ETHAMBUTOL Mechanism: • Inhibits arabinosyl transferases that are involved in mycobacterial cell wall synthesis Adverse effects: • Optic neuritis: red -green color blindness • Hyperuricaemia • Skin rashes & joint pain
  12. 12. PYRAZINAMIDE Mechanism: •Like INH, pyrazinamide inhibits mycolic acid biosynthesis but by a different mechanism. Adverse effects : •Dose-dependent hepatotoxicity •Hyperuricaemia •Anorexia, nausea, vomiting, fever and skin rashes
  13. 13. Streptomycin • It was the first effective drug developed for the treatment of tuberculosis. • Is an aminoglycoside antibiotic • Adverse effects: ototoxicity, nephrotoxicity and neuromuscular blockade
  14. 14. SECOND-LINE DRUGS In case of resistance to first-line agents In case of failure of clinical response to conventional therapy In case of serious treatment limiting adverse drug reactions
  15. 15. Treatment of Tuberculosis: • WHO recommends the use of multidrug therapy (MDT) for all cases of tuberculosis. The objectives of MDT are: – To make the patient non-infectious as early as possible by rapidly killing the dividing bacilli by using 3-4 bactericidal drugs. – To prevent the development of drug resistant bacilli. – To prevent relapse by killing the persisters or dormant bacilli. – To reduce the total duration of effective therapy.
  16. 16. Short Course Chemotherapy (SCC) Intensive phase: • Tuberculocidal drugs used • The main objective is to render the patient non-contagious. 2HRZE: INH Rifampin Pyrazinamide Ethambutol
  17. 17. Continuation phase: • This phase helps to eliminate persisters and prevents relapse 4HR: INH Rifampin
  18. 18. Antileprotic drugs
  19. 19. Classification:  Sulfone – Dapsone  Phenazine derivative – Clofazimine  Antitubercular drugs – Rifampicin Ethionamide  Other antibiotics – Ofloxacin Minocycline Clarithromycin
  20. 20. Dapsone Use : antileprotic agent Adverse effects:  Haemolytic anemia & methaemoglobinaemia – G6PD deficiency cases  Sulfone syndrome – fever, dermatitis, pruritus, anemia lymphadenopathy & hepatitis  GI disturbances, headache, itching  Peripheral neuropathy 2. Rifampicin – used in multidrug regimens – kills most of the bacilli
  21. 21. 3. Clofazimine: MOA – binds to mycobacterial DNA - inhibits its template function – anti-inflammatory effect Use : antileprotic agent Adverse effects:  Accumulates in tissues : red-to-brown discoloration of the skin  Pigmentation of the conjunctiva & cornea  GI disturbances
  22. 22. Treatment of Leprosy Paucibacillary :- Dapsone:100mg daily Rifampin:600mg once a month-Supervised. Duration:- 6 months. Multibacillary Leprosy:- Dapsone:- 100mg daily Rifampin:- 600mg once a month supervised Clofazimine:- 300mg once a month supervised,50 mg daily. Duration:- 24 Months.

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