Anti tuberculosis drug

Management and treatment of tuberculosis presentation

1. Antimycobacterial drugs

2. Pres ented to: Dr. Jamshed Akbar Presented by: Maria Aslam Nimra Jahangir Zoha Javed Aqsa Rabbani

3. Contents: Tuberculosis Drugs 1 st and 2 nd line Isoniazid Rifampin Ethambutol Pyrazinamide

4. Tuberculosis

5. TUBERCLOSIS Tuberculosis is an infectious disease caused by the mycobacterium tuberculosis. It primarily involves; Lungs But my attack most of the organs of the body.

6. The clinical features are as follow; Fever Anorexia Anemia Sputum Weight loss Sweating at night time Enlarge lymph nodes. Tubercle formation Necrosis and fibrosis of lungs. CLINICAL FEATURES

7. ANTI-MYCOBACTERIAL DRUGS First line or standard drugs: Isoniazid(INZ). Rifampicin. Ethambutol . Streptomycin. Pyrazinamide

8. Second line or reserve drugs: Second line or reserve drugs: They are used when the first line drugs are failed to produce response or the micro-organisms are resistant to those drugs. Ciprofloxacin O- floxacin Amikacin Cycloserine Ethionamide Para- aminosalicylic acid

9. Note : The anti-tuberculosis drugs are given in combination to prevent the bacterial resistance to the drugs.

10. A ISONIAZID

11. ISONIAZID(INH) It is a most potent anti tuberculosis drug which absorb rapidly after oral administration in the GIT widely distributed and penitrat efficiently. It is active against intracellular and extracellular tuberculli bacilli. It can be given orally, I/M and intrathecal injection. The main disadvantage of INH is resistance developed within few weeks if taken alone.

12. PHARMACOKINETICS It is well absorbed in GIT , widely distributed in the body and excreted in the urine within 24 hours. Dose is 300mg orally in divided dosage form. Pyridoxin or vitamin B6 should be given to prevent neuritis.

13. MECHANISM OF ACTION Inhibition of biosynthesis of mycolic acid which are important constituent of mycobacterial cell wall. INH interfere with pyridoxin metabolism and induces pyridoxin deficiency.

14. ADVERSE EFFECTS Neurotoxicity Peripheral neuritis Hepatotoxicity Jaundice Hemolysis Allergic reactions Skin rashes and fever

15. DRUG INTERECTIONS Rifampicin should not be given with isoniazid because it increases the hepatotoxicity. It is contraindicated in epileptic and psychotic patients.

16. A B Group of structurally similar macrocytic antibiotics, which are first line oral agents for tuberculosis. Rifampin Rifabutin Rifapentine Rifamycins

17. A B C A B Semisynthetic derivative of rifamycin Has broader antimicrobial activity than isoniazid Rifampin

18. B A B C A B Rifampin Never given as a single agent in treatment of active tuberculosis Must be use in combination No cross resistance to other classes of antimicrobial drugs Rifampin

19. B B A B C A B Binds with β subunit of mycobacterial DNA Mechanism of action : Rifampin Blocks RNA synthesis

20. B B A B C A B Bactericidal for both intracellular and extracellular mycobacteria Effective against many gram positive and gram negative organisms Prophylactically used for individuals exposed to meningitis Antimicrobial spectrum :

21. B B A B C A B Resistance is caused by mutations in the affinity of the bacterial DNA—dependent RNA polymerase gene for the drug Resistance :

22. B B A B C A B Pharmacokinetics: Well absorbed after oral administration Distribution occurs to all body fluids and organs Drug is taken up by the liver and excreted through kidney

23. B B A B C A B Adverse effects: Harmless orange color to urine, sweat and tears Occasional adverse effects include: Rashes, thrombocytopenia and nephritis Hepatitis and death due to liver failure are rare. extending to acute renal failure, hemolytic anemia and shock flu like syndrome can occur with fever , chills and myalgia. Should be used judiciously in older patients, alcoholics, or chronic liver diseases

24. B B A B C A B Rifampin induces a number of phase I cytochrome P450 enzymes and phase II enzymes It can decrease the half lives of coadministered drugs that are metabolized by enzymes May necessitate higher dosages for coadministered drugs, a switch to drugs less affected by rifampin or replacement Drug interactions:

25. B B A B C A B Mycobacterial infections: Clinical uses Usually 600mg/d orally , must be administered with isoniazid or other anti-TB drugs. In short course therapies, 600mg daily or twice weekly for 6 months also in combo with other agents in some atypical mycobacterial infections and in leprosy 600 mg daily for 4 months as a single drug, is an alternative to isoniazid prophylaxis for patients with latent tb only

26. B B A B C A B Clinical uses Other indications : Oral dosage of 600mg twice daily for 2 days can eliminate meningococcal carriage 20mg/kg/day for 4 days used as prophylaxis in children with Haemophilus influenza type b disease. combined with a second agent is used to eradicate staphylococcal carriage Combination therapy is also indicated for treatment of serious staphylococcal infections such as osteomyelitis and prosthetic valve endocarditis

27. Brands

28. A B C A B C Ethambutol Effective only against mycobacteria Is Tuberclostatic drug Less effective than INH and Rifampin

29. Mechanism of action Not completely known. Have bacteriostatic activity Arabinosyl transferase Polymerization of: Arabinose   Arabinan

30. Clinical uses Clinical uses Used with other medications to treat T-B. Works by stopping growth of bacteria. Only treat bacterial infection not viral.

31. ADR’s Visual disturbances such as: Decreased visual activity Red-green color blindness Optic neuritis and possible retinal damage. Gastrointestinal symptoms such as vomiting, nausea. Skin rash Fever

32. Containdications and precautions Optic neuritis Pregnancy without combination Decrease renal excreation Vision must be checked regularly

33. Pharmacokinetics Well absorbed orally 75-80% absorbed in GIT Distributed to most tissues including CNS Large fraction(50%) is eliminated in unchange form in urine within 24 hrs T1/2 is 3-4 hrs

34. Adult 15-25 mg/kg Paedriatic 15 mg/kg( maintainance as required) 25 mg/kg(initially for 60 days) Dose It is used in pregnancy  (category B).

35. Brands

36. Myrin P Conposition: Ethambutol :300mg INH :75 mg Rifampicin :150mg

37. Myrin P dose: 15mg/kg recommended after and before 1-2 hrs meal. Age: 30-39=2 tablets 40-54=3 tablets 55 and above=4 tablets

38. A B PYRAZINAMIDE

39. PYRAZINAMIDE Close analog of isoniazid Pro-drug ( Pyrazinoic acid) Bacteriostatic It is on the World Health Organization's List of Essential Medicines

40. MECHANISM OF ACTION

41. ADR’s Hepatotoxicity Hyperuricemia Allergic reactions

42. Side Effects

43. Pharmacokinetics well absorbed from the gastrointestinal tract widely distributed in body tissues, including inflamed meninges Metabolized by the liver Metabolites are renally no cross-resistance

44. Drug Interactions Pyrazinamide + BCG Pyrazinamide + Cholera vaccine Pyrazinamide + Leflunomide Pyrazinamide + Typhoid vaccine

45. Recommended dose for adults : Drug Dose mg /kg Dose range mg/kg Rifampin 10 8-12 INH 5 4-6 Pyrazinamide 25 20-30 Ethambutol 15 15-25 Streptomycin 15 12-18

46. Recommended dose for children : Drug Dose mg /kg Dose range mg/kg Rifampin 15 10-20 INH 10 7-15 Pyrazinamide 35 30-40 Ethambutol 20 15-25 Streptomycin is contraindicated.

47. Recommended dose according to weight: Weight more than 55 kg is: INH:300 mg Rifampin:600 mg Ethambutol:750 mg Pyrazinamide:1500mg

48. Brands

49. Multi-drug resistance: MDR T-B caused by bacteria which are resistant to treatment with at least two of the most powerful 1 st line anti-TB medication(rifampin &INH).

50. Drug interaction: INH: warfarin food antacid Rifampin: Decrease half life of co-administered drugs Contraceptives Warfarin Ethambutol : antacid containing aluminium -hydroxide. Pyrazinamide: Leflunomide Typhoid Vaccine