1. Under Guidance Of Presented by
Mrs.K.Chandana POLUNAVAKISHORE
Asst.Professor 12T21S0108
CMR COLLEGE OF PHARMACY I- M.Pharmacy, Pharmacology
8/3/2013 CMR COLLEGE OF PHARMACY 1

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
• Conclusion
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3.  Discoverer of mycobacterium
tuberculosis (Robert Koch)
 24th March 1882 TB Day
•Discovery of staining
technique that identified
Tuberculosis bacillus
•Definite diagnosis made
possible 1890 (Robert Koch)
•Tuberculin discovered
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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 .
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5. • Tuberculosis (TB)
• Multidrug-Resistant Tuberculosis (MDR TB)
• Extensively Drug-Resistant Tuberculosis (XDR TB)
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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 disease
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7. (Conti..)
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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.
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9. (Conti..)
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10. •MTBC( M.tuberculosis complex )
M.bovis,M.africanum,M.microti
•Rod shaped, aerobic bacterium
mycobacterium tuberculosis.
•Acid fast bacilli.
• Cell wall is lipid rich with mycolic acid
which is essential & unique component.
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11. (Conti..)
Infection - Immunity
•Bacterial entry
•T Lymphocytes.
•Macrophages.
•Epitheloid cells.
•Proliferation.
•Central Necrosis.
•Giant cell formation.
•Fibrosis.
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12. (Conti..)
Mode of transmission
• Inhalation
•Ingestion
•Inoculation
•Transplacental route
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13. DIAGNOSIS
• Tuberculin skin test or Quanti-
FERON® blood test
• CXR
• Sputum specimens to identify
organisms and their drug sensitivity
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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
• Gatifloxacin
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15. FDA ok’s new drug approval..
Sirturo (bedaquiline) has been approved by the FDA as part of
combination therapy for adults with multi-drug resistant tuberculosis.
This is the first TB medication to be approved in four decades, the
FDA informed.
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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.
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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.
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18. MECHANISM OF ACTION
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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.
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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.
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21. Two Phase 2 Clinical Trials
(Conti..)
•The FDA looked at two Phase 2 clinical trials to determine
Sirturo's 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
patient's 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.
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22. ADR EFFECTS
 QT Prolongation
Hepatic-related Adverse Drug Reactions
Drug Interactions
HIV-TB Co-Infected Patients
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23. CONCLUSION:
“A decision to test is a decision to treat.”
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24. REFERENCE:
• FDA Advisory Committee recommends accelerated approval of
bedaquiline for drug-resistant TB (http://www.sarpam.net )
• http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements
/ucm333695.html
• Text book of pathology by Harsh Mohan p.no.149-156
• 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.
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25. • http://www.medindia.net/patients/patientinfo/tuberculosis_treatme
nt.htm
• . http://www.webmd.com/lung/understanding-tuberculosis-
treatment
• .http://www.ncbi.nlm.nih.gov
• http://www.theunion.org/index.php/en/what-we-
do/tuberculosis/multidrug-resistant-tb-mdr-tb
• http://www.cdc.gov/tb/
• http://www.who.int/topics/tuberculosis/en/
• http://www.sarpam.net
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26. Any queries ????????????
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27. Be United Eliminate Tuberculosis.
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