ANTI - TUBERCULOSIS DRUG - PHARMACOLOGY

Here Describe the anti - tuberculosis drug with the classification, dose , route , MOA , side effects , adverse effects

1. ANTI- TUBERCULAR DRUGS Present By – Kunj Mesariya

2. Anti-tubercular drugs, also known as anti-tuberculosis drugs or TB drugs, are medications used to treat tuberculosis (TB), a bacterial infection caused by Mycobacterium tuberculosis. current treatment of tb is based on drugs that are more than 40 years old the discovery of streptomycin , the first effective antituberculosis agent INTRODUCTION

3. Ethionamide Thiacetazone Amikacin Para – aminosalicylic acid Capreomycin Cycloserine Ciprofloxacin Rifabutin Kanamycin Rifapentine Classification of anti – TUBERCULOSIS DRUG First – line drugs Second – line drugs Isoniazid Rifampicin Pyrazinamide Ethambutol Streptomycin

4. FIRST-LINE DRUGS

5. Drug Mechanisms of action Dose / Route 150 mg or 2.5 mg/kg Oral 1) Isoniazid (INH/H) Bactericidal; its mechanism of action is not fully known, but isoniazid may inhibit the synthesis of mycolic acid, which are important componentof mycobacterial cell wall resulting in cell wall disruption

6. Contraindication Previous INH hepatic injury or reaction Acute liver disease Hypersensitivity Adverse effect Peripheral neuritis, central nervous system (CNS) toxicity: Seizures, psychosis Hepatitis Minor effects like anorexia, gastrointestinal (GI) discomfort, fever and allergic reactions Hemolysis: In patients with G6PD Pyridoxine deficiency Hypersensitivity

7. Remark Peripheral neuritis due to interferencewith utilization and increased excretion of pyridoxine can be avoided by giving prophylactic pyridoxine (10-50 mg) with INH

8. Drug Mechanisms of action Dose / Route 2) Rifampicin(R) Bactericidal ; it inhibits DNA-dependent RNA polymerase activity in bacterial cells but not inmammalian cells 450-600 mg / oral Contraindication Hypersensitivity to rifamycins Concomitant Administration of live bacterial vaccines Contraindicated inpatients receiving ritonavir-boosted saquinavir ,because of increase drisk of severe hepatocellular toxicity

9. Adverse effect Hepatitis and hepatotoxicity . Serious hypersensitivity Thrombocytopenia , hemolytic anemia Renal failure , nephritis . CV : Hypotension and shock Respiratory : Shortness of breath CNS : Rare cases of organic brain syndrome ( i.e. confusion , lethargy , ataxia , dizziness and blurring of vision ) ; peripheral neuropathy . Gl : Nausea , vomiting , diarrhea . Orange - red staining of all body fluids Remark Acts on intra - and extra - cellular organisms , persisters and drug - resistant organisms

10. Drug Mechanisms of action Dose / Route Contraindication Pyrazinamide ( Z or PZA ) Bactericidal mechanism, (Z or PZA) of action is unknown pyrazinoicacid (POA), the active moiety of PZA, has beenshown to inhibit various functions at acid pH in M. tuberculosis 300 – 400 mg / Oral Severe Liver damage Acute gout Hypersensitivity

11. Adverse effect Remark Hypersensitivity reactions Bleeding tendencies , sideroblastic anemia . Hepatotoxicity , anorexia , nausea and vomiting , dysuria , malaise and fever Arthralgia Hyperuricemia Kills intracellular organisms ; more active in acidic pH Not be resumed If signs of hepatocellular damage hyperuricemia

12. Drug Mechanisms of action Dose / Route Contraindication 4 ) Ethambutol Bacteriostatic ; it inhibits the incorporation of mycolic acids into the mycobacterial cell wall by inhibiting certain enzymes ( arabinosyl transferases ) involved in it 800 – 1000 mg Or 25 mg/kg. / oral Hypersensitivity Optic neuritis

13. Adverse effect Remark Optic neuritis with decreased visual acuity and red - green color blindness Acute gout or hyperuricemia Abdominal pain Anaphylaxis Peripheral neuritis Inhibit tubercle bacilli in the walls of cavities

14. Drug Mechanisms of action Dose / Route Contraindication Streptomycin Bactericidal 750 – 1000 mg IM Hypersensitivity to streptomycin or other aminoglycosides Severe hypersensitivity to sulfites Concomitant live bacterial vaccines

15. Adverse effect Remark Ototoxicity , nephrotoxicity neurotoxicity Nausea and Vomiting Drug fever Hypotension Acts on extracellular organisms Streptomycin therapy is not commonly used for the full duration of therapy , because of toxicity concerns

16. SECOND -LINE DRUG

17. Drug Thiacetazone Mechanisms of action Bacteriostatic; low efficacy; delays development of resistance to other drugs Dose / Route 150 mg or 2.5 mg/kg Oral Contraindication Hypersensitivity to thiacetazone semicarbazoneor other Human immunodeficiency virus (HIV)infection Hepatic failure

18. Adverse effect Remark Ototoxicity , nephrotoxicity neurotoxicity Nausea and Vomiting Drug fever Hypotension Acts on extracellular organisms Streptomycin therapy is not commonly used for the full duration of therapy , because of toxicity concerns

19. Drug Mechanisms of action Dose / Route Contraindication Ethionamide Inhibits mycolic acid synthesis, an essentialcomponent ofthebacterial cell wall 10-20 mg/kg/day oral Hypersensitivity to ethionamide Severe hepatic or renal dysfunction

20. Adverse effect Postural hypotension Depression Dizziness , drowsiness , headache Peripheral neuropathy Psychosis Photosensitivity Allergic reaction Gynecomastia , impotence Hypoglycemia Anorexia , dyspepsia , diarrhea nausea , metallic taste , vomiting Thrombocytopenia Elevated liver transaminases Hepatitis Optic neuritis , visual changes

21. Drug Mechanisms of action Dose / Route Para-aminosalicylic acid (PAS) There are two mechanisms responsible for PAS bacteriostatic action against M.tuberculosis Firstly , PAS inhibits bacterial folic acid synthesis . Secondly , PAS may inhibit the synthesis of the cell wall component , mycobactin , thus reducing iron uptake by M. tuberculosis . 200 – 300 mg/kg/day per os

22. Adverse effect Contraindication Gl intolerance – nausea , vomiting diarrhea , and abdominal pain Hypersensitivity reactions : Fever , exfoliative dermatitis Infectious mononucleosis – like or lymphoma – like syndrome Leukopenia , agranulocytosis , thrombocytopenia , Coombs ‘ positive hemolytic anemia Jaundice , hepatitis . Pericarditis Hypoglycemia Optic neuritis Encephalopathy Loeffler’s syndrome . Hypersensitivity End – stage renal disease

23. Drug Mechanisms of action Dose / Route Cycloserine Inhibits alanine racemase and D – alanine : d – alanine ligase ; both enzymes are essential in the synthesis of peptidoglycan and subsequently in cell wall biosynthesis and maintenance 500 – 750 mg oral in 2-3 divided doses or 10-20 mg/kg day

24. Adverse effect Contraindication Hypersensitivity Alcohol use Severe renal dysfunction History of seizure disorder , depression , severe anxiety or psychosis CNS related : Convulsions , seizures , slurred speech , paralysis , somnolence and unconsciousness Hypersensitivity and allergic reaction

25. Drug Mechanisms of action Dose / Route Rifabutin Bactericidal ; it inhibits DNA – dependent RNA polymerase activity in bacterial cells but not in mammalian cells 300 mg daily Oral Contraindication Hypersensitivity to rifamycin Concomitant live bacterial vaccines

26. Adverse effect Myositis and uveitis Diarrhea , fever , heartburn , indigestion , loss of appetite , nausea , skin itching and / or rash ‘ Flu – like ‘ symptoms Thrombocytopenia Hepatitis Other adverse effects similar to Rifampicin

27. Drug Mechanisms of action Dose / Route Rifapentine Bactericidal ; it inhibits DNA – dependent RNA polymerase activity in bacterial cells but not in mammalian cells Weekly once 10-14 kg : 300 mg 14-25 kg 450 mg > 25-32 kg 600 mg > 32-49.9 kg : 750 mg 50 kg or more : 900 mg maximum

28. Adverse effect Contraindication Hepatitis Other adverse effect similar to rifampicin Hypersensitivity to rifamycins Monotherapy Porphyria

29. Drug Mechanisms of action Dose / Route Clofazimine The mode of action of clofazimine is not defined ; Studies have implicated membrane perturbations in Staphylococcus aureus , inhibition of phospholipase A2 and effects on potassium transporters . 50-100 mg oral Bd/od

30. Adverse effect Contraindication Hypersensitivity Gl toxicity : Abdominal and epigastric gastric pain , diarrhea nausea , vomiting , Gl intolerance Reddish black reversible skin discoloration Eye / conjunctival pigmentation Discoloration of urine , feces , sputum , sweat Elevated blood sugar Elevated erythrocyte sedimentation rate test ( ESR ) . CNS : Headache , dizziness , drowsiness , fatigue and taste disorder Ichthyosis and dryness ; rash and pruritus , acne form eruptions , phototoxicity

31. Drug Mechanisms of action Dose / Route Bedequiline Inhibits mycobacterial adenosine 5 ' - triphosphate ( ATP ) synthase , an enzyme essential for the generation of energy in Mycobacterium tuberculosis Week 1-2 400 mg /day per ps (PO) for 2 week Week 3-24 200 mg 3 time/week

32. Adverse effect Nausea ( 38 % ) Arthralgia ( 32.996 ) Headache ( 27.8 % ) Transaminases increased ( 8.9 % ) Blood amylase increased ( 2.596 ) QT prolongation

33. Drug Fluoroquinolones Ciprofloxacin , ofloxacin , moxifloxacin , gatifloxacin , levofloxacin and sparfloxacin are used as second - line tuberculosis ( TB ) drugs ; for further information on individual drugs refer to fluoroquinolones . Drug Linezolid Refer to Oxazolidinone Drug Amikacin , kanamycin and capreomycin Refer to Aminoglycoside

34. NURSING RESPONSIBILITY Assess Signs of anemia ( Hb ) , fatigue , liver function test , renal function Allergy to any of the drugs in the regimen Isolation of patients and barrier nursing Administer Isoniazid ( INH ) and Rifampicin 1 hour before food Other agents 2 hour after food Antiemetics as prescribed if vomiting

35. PATIENT EDUCATION Importance of compliance with dosage schedule , duration is necessary . Rifampicin may color the body fluids red – orange . That scheduled follow up with prescriber should be kept since relapse can occur . To avoid alcohol while taking the drug . To report flu – like symptoms : Excessive fatigue , anorexia , vomiting , sore throat , unusual bleeding , and yellowish discoloration of skin / eyes . To dispose of sputum carefully and to wear mask to prevent transmission . Advises the patient to take foods rich in vitamin B6 otherwise neuropathies can develop