Treatment of tb with sirturo


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Treatment of tb with sirturo

  1. 1. Under Guidance Of Presented by Mrs.K.Chandana POLUNAVAKISHORE Asst.Professor 12T21S0108CMR COLLEGE OF PHARMACY I- M.Pharmacy, Pharmacology 8/3/2013 CMR COLLEGE OF PHARMACY 1
  2. 2. CONTENTS • Introduction of TB • FDA ok’s new drug • Definitions approval • Pathophysiology • What is sirturo ? • Diagnosis • Structural features of sirturo • Management of TB • Mechanism of action • SIRTURO treatment • ADR effects • Conclusion8/3/2013
  3. 3.  Discoverer of mycobacteriumtuberculosis (Robert Koch) 24th March 1882 TB Day •Discovery of staining technique that identified Tuberculosis bacillus •Definite diagnosis made possible 1890 (Robert Koch) •Tuberculin discovered8/3/2013 3
  4. 4. (Conti..)  Tuberculosis is a chronic Infectious Disease - caused by M.tuberculosis/M.bovis - mainly affecting the lung causing PTB - also affect other parts causing EPTB  Characterized by • Cough lasting > 3 wks and not respond to usual antibiotics. • Production of purulent, sometimes blood- stained sputum . • Evening rise of temp. • Night sweats. • Weight loss .8/3/2013 4
  5. 5. • Tuberculosis (TB) • Multidrug-Resistant Tuberculosis (MDR TB) • Extensively Drug-Resistant Tuberculosis (XDR TB)8/3/2013 5
  6. 6. Multidrug-Resistant Tuberculosis (MDR TB) • Multidrug-resistant TB (MDR TB) is TB that is resistant to at least two of the best anti-TB drugs, isoniazid and rifampicin. • These drugs are considered first-line drugs and are used to treat all persons with TB disease8/3/2013 6
  7. 7. (Conti..)8/3/2013 7
  8. 8. Extensively Drug-Resistant Tuberculosis (XDR TB) • XDR TB is a less common form of multidrug-resistant TB in which TB bacteria have changed enough to circumvent the two best antibiotics, INH and RIF, as well as most of the alternative drugs used against MDR TB. • These second-line drugs include any fluoroquinolone, and at least one of the other three injectable anti-TB drugs: amikacin, kanamycin, or capreomycin.8/3/2013 8
  9. 9. (Conti..)8/3/2013 9
  10. 10. •MTBC( M.tuberculosis complex ) M.bovis,M.africanum,M.microti•Rod shaped, aerobic bacteriummycobacterium tuberculosis.•Acid fast bacilli.• Cell wall is lipid rich with mycolic acidwhich is essential & unique component.8/3/2013 10
  11. 11. (Conti..) Infection - Immunity •Bacterial entry •T Lymphocytes. •Macrophages. •Epitheloid cells. •Proliferation. •Central Necrosis. •Giant cell formation. •Fibrosis.8/3/2013 11
  12. 12. (Conti..) Mode of transmission • Inhalation •Ingestion •Inoculation •Transplacental route8/3/2013 12
  13. 13. DIAGNOSIS • Tuberculin skin test or Quanti- FERON® blood test • CXR • Sputum specimens to identify organisms and their drug sensitivity8/3/2013 13
  14. 14. MANAGEMENT OF TB First line drugs Second line drugs • Isoniazid (INH) • Cycloserine • Rifampin (RIF) • Ethionamide • Pyrazinamide (PZA) • Amikacin/kanamycin • Ethambutol (EMB) • Capreomycin • Streptomycin • P-Amniosalicylic acid (PAS) • Levofloxacin • Moxifloxacin • Gatifloxacin8/3/2013 14
  15. 15. FDA ok’s new drug approval..Sirturo (bedaquiline) has been approved by the FDA as part ofcombination therapy for adults with multi-drug resistant tuberculosis.This is the first TB medication to be approved in four decades, theFDA informed.8/3/2013 15
  16. 16. What is sirturo? • Also known Bidaquiline or TMC207 • Is an diarylquinoline anti-tuberculosis drug. •It was described for the first time in 2004 at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) meeting Late-Breaker Session, after the drug had been in development for over seven years. •Sirturo is the first medicine specifically designed for treating multi-drug-resistant tuberculosis.8/3/2013 16
  17. 17. Structural features of sirturo• Diarylquinoline derivative.• IUPAC: (1R,2S)-1-(6-Bromo- 2-methoxy-3-quinolinyl)-4- (dimethylamino)-2-(1- naphthyl)-1-phenyl-2-butanol.• The high specificity of Bedaquiline for Mycobacteria.8/3/2013 17
  18. 18. MECHANISM OF ACTION8/3/2013 18
  19. 19. (Conti..) • By inhibiting mycobacterial adenosine 5-triphosphate (ATP) synthase. • Inhibiting the proton pump of M. tuberculosis and therefore interfering with the rotation properties of the transmembrane disk, leading to ATP depletion.8/3/2013 19
  20. 20. SIRTURO treatment • SIRTURO was administered as 400 mg once daily for the first two weeks and as 200 mg three times per week for the following 22 weeks.8/3/2013 20
  21. 21. Two Phase 2 Clinical Trials (Conti..) •The FDA looked at two Phase 2 clinical trials to determine Sirturos safety and efficacy. In the first trial, patients were randomly selected to be treated with Sirturo alongside other TB medications. •In the second trial patients received Sirturo plus other TB medications. This study is ongoing. •In both studies, the aim was to determine how long it took for the patients sputum to be free of M. tuberculosis. •In the first trial, the Sirturo-combination therapy patients sputum became M. tuberculosis free in 83 days, versus 125 days for those on placebo. The second trial has so far supported the results of the first trial.8/3/2013 21
  22. 22. ADR EFFECTS  QT Prolongation Hepatic-related Adverse Drug Reactions Drug Interactions HIV-TB Co-Infected Patients8/3/2013 22
  23. 23. CONCLUSION: “A decision to test is a decision to treat.”8/3/2013 23
  24. 24. REFERENCE:• FDA Advisory Committee recommends accelerated approval of bedaquiline for drug-resistant TB ( )• /ucm333695.html• Text book of pathology by Harsh Mohan• Diacon AH et al. Randomized pilot trial of eight weeks of bedaquiline (TMC207) treatment for multidrug-resistant tuberculosis: long-term outcome, tolerability, and effect on emergence of drug resistance. Antimicrobial Agents and Chemotherapy 56, no. 6: 3271-3276, June 2012.8/3/2013 24
  25. 25. • nt.htm• . treatment• .• do/tuberculosis/multidrug-resistant-tb-mdr-tb••• http://www.sarpam.net8/3/2013 25
  26. 26. Any queries ????????????8/3/2013 26
  27. 27. Be United Eliminate Tuberculosis.8/3/2013 27
  28. 28. 8/3/2013 28