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Tb seminar by rs
- 1. TUBERCULOSIS Submitted To : Dr.KANCHAN VOHRA Assistant Professor Submitted By : Mohd. Rafi Bhat Department of pharmaceutical science & Drug Research
- 2. Introduction Tuberculosis (TB) isa disease caused by bacteria called Mycobacterium tuberculosis. The bacteria usually attack the lungs, but they can also damage other parts of the body.
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- 4. Aetiology TB is causedby tubercle bacilli, which belong to the genus Mycobacterium. These form a large group but only three relatives (Mycobacterium tuberculosis complex) are obligate parasites that can cause TB disease. M. tuberculosis complex: M. tuberculosis, M. bovis, M. africanum Discovered in 1882 by Robert Koch.
- 5. Examples of factorsthat increase risk of developing TB HIV positive Injecting drug users Solid organ transplantation, jejunoileal bypass or gastrectomy Haematological malignancy, for example leukaemia and lymphomas Chronic renal failure or receiving haemodialysis
- 6. Symptoms The symptoms andsigns of TB include: Cough for 3 weeks or more/productive cough Sputum usually mucopurulent or purulent Haemoptysis not always a feature Fever may be associated with night sweats Tiredness Weight loss variable Anorexia variable Severe Symptoms Persistent cough Chest pain Coughing with bloody sputum Shortness of breath Urine discoloration Cloudy & reddish urine Fever with chills. Fatigue
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- 10. Clinical diagnosis The clinicaldiagnosis of TB disease is based on the symptoms and signs in the patient together with chest radiography, microscopy of sputum followed by culture and tuberculin skin testing. Blood-based immunological tests, introduced in the last few years, will play an increasingly important role in TB diagnosis. These tests can distinguish between TB infection and previous BCG vaccination.
- 11. Microbiological Microbiological investigations areundertaken to assess the infectious state (mycobacteria causing TB and other mycobacteria). Determine the drug-susceptibility patterns of the infecting organisms, to ensure that the drugs . Investigations comprise microscopy, culture, drug-susceptibility testing and strain typing. Direct microscopy of sputum is the simplest and quickest method of detecting the infectious patient, by looking for acid-fast bacilli. A minimum of three sputum samples, one of which should be early morning, should be collected from patients with suspected respiratoryTB.
- 12. Cultures Direct microscopy isnot as useful in non-pulmonary disease, any specimens taken should be sent for culture. Lowenstein–Jensen medium, growth may take up to 6 weeks. Polymerase chain reaction (PCR)-based tests can also detect M. tuberculosis complex in clinical specimens. A rapid test is available for assessing rifampicin resistance in individuals thought tohave drug-resistant TB. A positive result indicates the need to assess susceptibility to other first line anti-TBdrugs. DNA fingerprinting, or strain typing, is useful in the public health management ofTB. New method, mycobacterial (MIRU/VNTR) 24-loci strain typing, became available in UK
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- 15. Chest radiography The chestradiograph is a non-specific diagnostic tool, as TB may present as virtually any abnormality on chest radiography. This is why microbiological evidence of confirmation should be sought. Pulmonary TB may appear as bronchopneumonia with confluent shadowing, without cavitation. Cavitation may be seen, the incidence can vary between 10% and 30%. Uncharacteristic radiological patterns may occur in the presence of HIV infection.
- 16. Diagnosis in peoplewith HIV TB can occur early in the course of HIV infection and may therefore be diagnosed before the patient is known to be HIV positive. The possibility of HIV infection in people with TB should therefore be considered, and testing for the virus is appropriate in those with risk factors for HIV. Early in the course of HIV infection, before serious immunodeficiency occurs, TB is more likely to present with typical clinical features, and a positive tuberculin skin test, with cavitation and/or pleural disease on chest radiography. In the late stages of HIV infection show chest findings and extra pulmonary disease.
- 17. Treatment In treating TB,a number of factors are important: • Choice of drugs • Length of treatment • Co-morbidity especially HIV infection, liver and renal diseases • Adherence to treatment by the patient. It is important to tailor the management of the patient according to his or her situation, rather than just focus on the drug treatment of TB, as other factors in the patient's life may affect adherence. Bacille Calmette Guerin (BCG). First used in 1921. Only vaccine available today for protection against tuberculosis. It is most effective in protecting children from the disease.
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- 19. Drug treatment Treatmentwith anti-TB drugs has two main purposes: • to cure people with TB, provided the bacilli are drug sensitive • to control TB, by either preventing the development of infectious forms With the advent of effective anti-TB chemotherapy, patients no longer needed treatment in a sanatorium. Results with regimens containing isoniazid together with p-aminosalicylate (PAS) or ethambutol, and sometimes streptomycin, gave excellent results. Treatment was required for 18–24 months if relapse was to be prevented. The availability of pyrazinamide and, more importantly, rifampicin made shorter courses of treatment a possibility. Most regimens in the developed world now contain isoniazid and rifampicin, which are the two most important drugs together with pyrazinamide and possibly with another agent, such as ethambutol.
- 20. Treatment The recommended standardtreatment regimen for respiratory and most other forms of TB •rifampicin, isoniazid, pyrazinamide and ethambutol for the initial 2 months (initial phase) • a further 4 months of rifampicin and isoniazid (continuation phase). A longer period of treatment than the standard 6 months is needed for meningealTB and where there is direct spinal cord involvement. Patients should be started on the standard treatment Regimen on clinical diagnosis.
- 21. The purpose ofthe concurrent use of four drugs in the initial phase is to reduce the bacterial population as rapidly as possible and prevent the emergence of drug-resistant bacteria. It is important, however, to ensure the combination product contains the required dose of the constituent drugs. Patients with suspected drug reactions or drug-resistant TB should always be referred back to the specialist physician and the healthcare team supervisingtheir treatment.
- 22. DOTS DOTS - Directlyobserved treatment, short-course DOT means that a trained health care worker or other designated individual provides the prescribed TB drugs and watches the patient swallow every dose.
- 24. Drugs MOA Diagram IsoniazidInhibits mycolic acid synthesis. RIFAMPICIN Blocks RNAsynthesis by blocking DNA dependent RNApolymerase PYRAZINAMIDE •Bactericidal-slowly metabolizing organism within acidic environment of Phagocyte or caseous granuloma.
- 25. Drugs MOA Diagram ETHAMBUTOL•Bacteriostatic •Inhibition of Arabinosyl Transferase STREPTOMYCIN •Inhibition of Protein synthesis by disruption of ribosomal function
- 26. ADRs and itsManagement
- 27. Drug-resistant TB MDR-TB iscaused by bacteria that are resistant to at least isoniazid and rifampicin,the most effective anti-TB drugs. MDR-TB results from either primary infection with resistant bacteria. XDR-TB is a form of TB caused by bacteria that are resistant to isoniazid and rifampicin, fluoroquinolone and any of the second-line anti-TB injectable drugs including amikacin, kanamycin or capreomycin
- 28. Drugs used inMDR-TB Bedaquiline ----- trade name – sirturo Works by blocking an enzyme inside the M. tuberculosis bacteria called ATP synthase.This enzyme is used by the bacteria to generate energy. Without the ability to generate energy , the TB bacteria die and the patient’s condition can start to improve. Used in combination with other TB drugs. If resistant to main TB drugs – isoniazid and rifampicin. DOSE- 400mg a day for four weeks and then 200 mg taken three times a week.
- 29. delamanid Trade name–Deltyba Class- Nitroimidazoles. Dose- 50 mg tab. Two tabs. Twice a day with food.for six months. Inhibiting the synthesis of mycobacterial cell wall components , methoxy mycolic acid and ketomycolic acid.
- 30. Pretomanid Another nitroimidazole-oxazole currentlybeing developed by the TB Alliance. It also can potentially be used for the treatment of both drug sensitive and drug resistant TB, and it has also shown activity against both latent and active TB.