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Antitubercular Drugs

First line

  1. INH                      
  2. Rifampin                      
  3. Pyrizinamide                        
  4. Ethambutol          
  5. Streptomycin         

Second line drugs

  1. PAS                      
  2. Thiocetazone                        
  3. Etthionamide        
  4. Cycloserine          
  5. Capreomycin                        
  6. Kanamycin           
  7. Amikacin                      
  8. Fluroquinolones (Ciprofloxacin, Levofloxacin , Gatifloxacin, Sparfloxacin)  

Individual drugs

  1. INH
    1. Isonicotinic hydrazide; fastest acting ATT
    2. Acts against, intra & extracullar bacteria
    3. Pro-drug
    4. Goes to bacteria, gets converted into active moiety
    5. Inhibits mycolic acid synthesis
    6. Resistance in INHA or KatG gene leads to development of resistance

p/k: 

  1. Well absorbed
  2. Short acting
  3. Best caseous material penetration
  4. Undergoes acetylation
    1. Slow acetylators
    2. Fast acetylators
    3. Indians slow acetylators: have neuropathy as MC side effect
    4. Westerners: fast acetylators-hepatitis as MC side effect  
  5. Metabolites eliminated by kidneys
  6. Dose in renal failure, not modified

Use

  1. Prophylaxis of TB
  2. DOC: Latent TB
  3. Drug interactions
     
    i. INH is an enzyme inhibitor; increases plasma levels of phenytoin

Side effects

  1. MC-neuropathy-more common in slow acetylators (-Indians slow acetylators)
    1. Rare in children
    2. More common in alcoholics
  2. Optic neuritis (rare)
  3. Hepatitis is-rare in children; common in alcoholics
  4. “Hand shoulder” syndrome
  5. Transient amnesia
  6. Agranulocytosis  

2. Rifampicin

  1. Rifamycin derivaive, obtained from streptomyces
  2. Slowly acting
  3. Acts upon slow growing/intermittent/spurters
  4. Resistance occurs due to mutation in Rifo B gene
  5. MAO:
  6. Blocks, DNA dependent RNA polymerase

p/k:

  1. Well absorbed              
  2. Deacetylated                        
  3. Undergoes elimination by bile
  4. Short acting         
  5. Potent enzyme inducer            
  6. Enters CSF

Uses

  1. Tb                
  2. Leprosy                                        
  3. Legionella    
  4. Meningococci                
  5. Staphylococcal infections (including MRSA)    
  6. Brucella

Side effects

  1. MC-orange red discoloration of body fluids            
  2. Hepatitis
  3. Flu like symptoms                                
  4. Abdominal symptoms
  5. Cutaneous symptoms                            
  6. Reversible renal failure; rare

3. Ethambutol

  1. Weak ATT
  2. Bacteristatic
  3. Inhibits arabinoacyl transferase
  4. Well absorbed
  5. Not metabolized
  6. Eliminated by kidneys; accumulates in renal failure-CI
  7. Side effect-Optic neuritis (red-green* blindness)
  8. Hyperuricemia

*Green colour abnormalities are more common

 

4. Pyrizinamide

  1. Acid drug; acts like INH
  2. Most hepatotoxic ATT
  3. MAO like INH
  4. Slowly acting; formulated in acidic pH
  5. Not active against M. Kansasii
  6. Acts against dormant & semi-dormant bacteria-sterlizes TB cavities
  7. Prodrug; gets converted into active moiety in liver
  8. Hyperuricemia is MC side effect; Rx-aspirin
  9. Avoid if gout occurs
  10. Hepatitis; more common in pregnancy 

5. Streptomycin

  1. Bactericidal; acts only against extracellular bacteria
  2. Most vestibulotoxic
  3. Not absorbed orally
  4. Enters Tb cavities
  5. Does not enter CSF
  6. Avoided in pregnancy 

Second line

  1. PAS
    1. Prodrug; sulfonamide analogue
    2. Slowly acting
    3. Least potent
    4. Poorly absorbed
    5. MC side effect; GI upset
    6. Can interfere with thyroid function
    7. Malabsorption, peptic ulcer, thyroid abnormalities, sulfa allergy
  2. Thiocetazone
    1. Weak ATT
    2. Avoided in HIV infected patients as causes bone marrow depression/allergic reactions
    3. Allergies common in India 
  3. Ethionamide
    1. Drug like INH
    2. Interferes with thyroid function Neuropathy, hepatitis occur
       
      Rx-B6
  4. Linezolid
     
    a. New drug for Tb
  5. Capreomycin
    1. Slowly acting
    2. Bacteristatic
    3. Blocks cell wall synthesis
    4. Eliminated unchanged, CI renal failure
    5. CNS side effects occur-Rx-B6
  6. Kanamycin
  7. Capreomycin
  8. Amikacin
     
    Used in MDR Tb 

TB in special situations

  1. TB in pregnancy
    1. Same regimen as recommended by RNTCP guidelines but streptomycin is purely contraindicated.
    2. Pyrazinamide is also teratogenic but its use during pregnancy is permitted if benefit is more than risk.
    3. If pyrazinamide is not included in TB regimen, treatment is given for 9 months( 2 months HRE and 7 months HR)
  2. TB in renal failure
     
    INH+rifampin
  3. TB in HIV
     
    Same regimen as recommended by RNTCP but given for extened period (9 months)
  4. TB with liver disease
     
    Recommended drugs are: Streptomycin+ethambutol

Categories of tuberculosis

 

Cat-1

  1. New case              
  2. HIV Postive          
  3. Severe case          
  4. Extrapulmonary tuberculosis

Cat-2

  1. Failed          
  2. Defaulter              
  3. Relapse

Cat-3  

  1. There is no category 3 according to RNTCP 2010

Cat-4

  1. MDR tuberculosis





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