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Anti tb drugs cbme 2021 satya

This interesting ppt contains Anti TB drugs topic for II MBBS CBME students Illustrated with pictures and flowcharts..

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Anti tb drugs cbme 2021 satya

  1. 1. ANTITUBERCULAR DRUGS DR.V. Sathyanarayanan M.B.B.S., M.D., ACME Professor of Pharmacology, SRM MCH & RC, INDIA
  2. 2. COMPETENCY ACHIEVMENT 1:44 PH 1.44 Describe the first line antitubercular drugs, their mechanism of action, side effects and doses. 1:45 PH 1.45 Describe the drugs used in MDR and XDR tuberculosis
  3. 3. OUTLINE What is tuberculosis ? Symptoms First line drugs Second line drugs Newer drugs Treatment of tuberculosis : Goals & General principles Drug resistant tuberculosis Management ofADR Chemoprophylaxis TB in pregnancy & in AIDS
  4. 4. SPECIFIC LEARNING OBJECTIVES At the end of the session, learners shall be able to • Classify Antitubercular Drugs correctly. • Describe the mechanism of action, adverse effects, drug interactions and therapeutic uses of first line Antitubercular drugs rightly. • Describe the mechanism of action, adverse effects of Antitubercular drugs used in MDR and XDR tuberculosis rightly. • Enumerate the Antitubercular drug regimen with dosage accurately.
  5. 5. TUBERCULOSIS A chronic granulomatous disease caused by mycobacterium tuberculosis Major health problem 1/3 of world population infected Increased incidence because of HIV spread MDR tuberculosis is emerging
  6. 6. SYMPTOMS Persistent cough more than 3 weeks Evening rise of temperature Loss of appetite Loss of weight
  7. 7. ORGANS AFFECTED • Lungs • Lymph nodes • Bone • Brain
  8. 8. AFTER INH (1952) • Tuberculosis became curable
  9. 9. CLASSIFICATION
  10. 10. FIRST LINE DRUGS INH (1952) Rifampicin (1962) Pyrazinamide Ethambutol (1961) Streptomycin (1947) Have high efficacy and low toxicity Used routinely
  11. 11. SECOND LINE DRUGS Thiacetazone Ethionamide PAS Kanamycin Amikacin Capreomycin Have low efficacy or high toxicity or both Used in special circumstances only
  12. 12. NEWER DRUGS Ciprofloxacin , Ofloxacin , sparfloxacin, Moxifloxacin Clarithromycin Azithromycin Rifabutin Linezolid Bedaquiline, Delamanid
  13. 13. FIRST-LINE DRUGS
  14. 14. ISONIAZID
  15. 15. ISONIAZID ( INH ) Rapidly tuberculocidal Inhibit mycolic acid synthesis in the bacterial cell wall highly selective forTB bacilli Given alone produces resistance by mutation Orally absorbed & penetrates tissues Metabolized by acetylation Essential component of antitubercular regimen
  16. 16. ISONIAZID – ADR & D/I Well tolerated by most. peripheral neuritis, hepatitis, convulsions, rash, fever, optic neuritis D/I – increase phenytoin, warfarin, carbamazepine, diazepam levels Aluminium hydroxide inhibits INH absorption
  17. 17. INH – TOXICITY & PREVENTION Hepatotoxicity is seen in older people and alcoholics, reversible on stoppage of drug Pyridoxine given along with INH to prevent neurotoxicity
  18. 18. RIFAMPICIN
  19. 19. RIFAMPICIN Semisynthetic derivative of Rifamycin B Binds with beta subunit of DNA dependent RNA polymerase of bacteria  forms drug-enzyme complex Inhibits mRNA synthesis  bactericidal Orally absorbed, food interferes, has to be taken in empty stomach undergo enterohepatic circulation Attains high concentrations in CSF
  20. 20. RIFAMPICIN - ADVERSE EFFECTS hepatitis – dose related, reversible Flu like syndrome, abdominal syndrome, cutaneous syndrome, respiratory syndrome Urine, secretions become orange- red(harmless )
  21. 21. RIFAMPICIN - Other uses Important 1st line drug in leprosy Atypical mycobacterial infections 2nd choice for MRSA with doxycycline 1st line for brucellosis, prophylaxis of meningococcal meningitis, H.influenza meningitis, legionella pneumonia Alternative drug for anthrax
  22. 22. RIFAMPICIN – DRUG INTERACTIONS it is a microsomal enzyme inducer  failure of OC pills, decreases levels of sulfonylureas, anti HIV drugs, theophylline
  23. 23. RIFAMPICIN - ADVANTAGES Acts best on spurters and persisters Also act on semidormant bacilli Has good sterilizing action Has resistance preventing action Widely distributed
  24. 24. PYRAZINAMIDE
  25. 25. PYRAZINAMIDE Chemically similar to INH Weakly tuberculocidal More active in acidic medium Have good ‘sterilizing’ activity Inhibit mycolic acid synthesis Widely distributed & penetratesCSF well ADR – hepatotoxicity, hyperuricemia, fever, arthralgia, flushing, rashes, loss of diabetes control C/I – liver disease
  26. 26. ETHAMBUTOL
  27. 27. ETHAMBUTOL Tuberculostatic As active as S Inhibit arabinosyl transferases and Interfere with mycolic acid incorporation into cell wall Resistance develop slowly ADR – loss of visual acuity/colour vision due to optic neuritis, rash, fever, hyperuricemia CAUTION – renal disease C/I - < 6 years of age
  28. 28. STREPTOMYCIN
  29. 29. STREPTOMYCIN 1st AntiTubercular drug, supplemental 1st line drug Less effective than INH, Rifampicin Acts only on extracellular bacilli Penetrates tubercular cavities Does not cross CSF Resistance develops rapidly when used alone Has to be given I.M Has lower margin of safety ADR - Ototoxicity, nephrotoxicity Usage has declined ( used for the maximum of 2 months )
  30. 30. SECOND-LINE DRUGS
  31. 31. SECOND LINE DRUGS • Thiacetazone • Ethionamide • PAS • Kanamycin • Amikacin • Capreomycin • Have low efficacy or high toxicity or both • Used in special circumstances only
  32. 32. THIACETAZONE Tuberculostatic, low efficacy drug Hepatotoxic  discarded in the west Low cost Used with INH to prevent DRUG RESISTANCE ADR – hepatitis, bone marrow depression, stevens johnson syndrome, cerebral edema Reserve anti-TB drug Should not be used in HIV patients
  33. 33. PAS Related to sulfonamide Tuberculostatic Delays resistance Cause Hypersensitivity reactions, GI distress Very high dose ( 10 – 12 grams / day )  Poor patient acceptability Rarely used now ( only in resistantTB )
  34. 34. OTHER DRUGS • ETHIONAMIDE – Hepatotoxic, cause allergy, neuritis, gastric intolerance,CNS toxicity  seldom used  used only in case of resistance • CYCLOSERINE – An antibiotic with high CNS toxicity (sleepiness, headache, tremor, psychosis, suicidal tendencies, convulsions ) inhibits cell wall synthesis • KANAMYCIN,AMIKACIN, CAPREOMYCIN – more toxic antibiotics, reserve drugs in rare cases, given I.M
  35. 35. Second-line Anti-TB Drugs Weaker than first-line. Cause adverse reactions. Difficult for patient to tolerate Should be taken for long periods Very expensive. Cure rates are much lower than of patients susceptible to the first-line drugs.
  36. 36. NEWER DRUGS
  37. 37. NEWER DRUGS • CIPROFLOXACIN,OFLOXACIN, LEVOFLOXACIN, SPARFLOXACIN, MOXIFLOXACIN – Combination regimen in MDR tuberculosis, MAC infection in HIV patients, good tolerability, penetrates cells • MACROLIDES – CLARITHROMYCIN,AZITHROMYCIN - MDR tuberculosis, non tubercular mycobacteria • RIFABUTIN – Related to rifampicin, cross resistance seen, More active on MAC in AIDS, weak enzyme inducer • ADR  cause rash, myalgia, uveitis, granulocytopenia
  38. 38. BEDAQUILINE • Recent diarylquinoline drug • Act by novel mechanism • Inhibits mycobacterial ATP synthase  limits energy production within the mycobacterial cell • MICs are very low • No cross resistance • Well absorbed orally • Due to redistribution terminal half life is very long ( 160 days ) • Only for MDR-TB • ADR  NAUSEA, headache, arthralgia, prolongation of QTc interval, hepatotoxic
  39. 39. TREATMENT OF TUBERCULOSIS
  40. 40. THE GOALS OFTREATMENT Kill dividing bacilli – to relieve symptoms and non-contagious Kill persisting bacilli – to prevent relapse & to provide cure Prevent emergence of resistance – to prevent treatment failure • to provide adequate response
  41. 41. Antitubercular Therapy Effectiveness depends upon: Type of infection Adequate dosing Sufficient duration of treatment Drug compliance Selection of an effective drug combination
  42. 42. GENERAL PRINCIPLES Use Combinations of 2 or more drugs Combination of INH and R is synergistic which shortens the duration of therapy Single daily dose of all 1st line drugs is preferred Response is fast in the 1st few weeks Follow DOTS (directly observed treatment short course )
  43. 43. SHORT COURSE CHEMOTHERAPY Initial intensive phase – 2-3 months Continuation phase – 4-6 months
  44. 44. TREATMENT OF TUBERCULOSIS INH, rifampicin,pyrazinamide , ethambutol – for 2 months followed by INH, Rifampicin For 4 months
  45. 45. RESISTANT TUBERCULOSIS
  46. 46. MDRTB (MULTIDRUG -RESISTANT) Some die in 4-16 weeks 1 or more 2nd line drugs for 12-24 months Total of 5-6 drugs are given Intensive phase ( 6-9 months ) Continuation phase ( 18 months ) H resistance – RZE for 12 months H+R resistance – ZE+S/Kmc/Am/Cpr + Cipro/Ofl+- Etm
  47. 47. EXTENSIVELY DRUG RESISTENTTB MDR-TB CASES Resistant to at least 4 cidal drugs Virtually untreatable Mortality high Intensive phase ( 6-12 months ) – 7 DRUGS Continuation phase( 18 months ) – 6 DRUGS
  48. 48. MANAGEMENT OF SIDE EFFECTS
  49. 49. MANAGEMENT OF ADR Z – arthralgia ----- NSAIDs H- peripheral neuritis ------ pyridoxine E-optic neuritis ---- stop E R - hemolysis, thrombocytopenia- stop R H,R,Z – hepatotoxicity ---- stop all drugs till reaction clears , add S+E or C
  50. 50. CHEMOPROPHYLAXIS
  51. 51. CHEMOPROPHYLAXIS H 300mg daily for 6 months or High dose of INH ( 15mg/kg) +ONCE A WEEK Rifapentine (10 mg/kg) for 3 months
  52. 52. ROLE OF CORTICOSTEROIDS
  53. 53. ROLE OF CORTICOSTEROIDS Ordinarily should not be used Used under chemotherapeutic cover in MiliaryTB Hypersensitivity reactions MeningealTB, renalTB, pleural effusion Severe forms in AIDS patients CONTRAINDICATED IN INTESTINAL TB
  54. 54. TB IN PREGNANCY
  55. 55. TB IN PREGNANCY H,R, Z, E  SAFE 2HRZE +4 HRE S is contraindicated ( Ototoxic ) To Avoid Z 2HRE +7HR During lactation baby should be watched, infant has to be given BCG vaccine + INH prophylaxis,+ Pyridoxine
  56. 56. TUBERCULOSIS IN AIDS More severe ADR and drug interactions more common ATT duration longer HRZE for 2 months +HRE for 4- 7 months Pyridoxine to be added Also receive co-trimoxazole Rifabutin for Rifampicin
  57. 57. MAC INFECTION IN AIDS • Clari/azithro + E + Rifabutin + one FQ for 2-6 months followed by clari /azithro + E/ one FQ for 12 months
  58. 58. THEME :“STOPTB IN MY LIFETIME.”
  59. 59. THANKYOU

This interesting ppt contains Anti TB drugs topic for II MBBS CBME students Illustrated with pictures and flowcharts..

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