Monday, 27 July 2020

ANTI -TUBERCULAR DRUGS



Tuberculosis is a chronic granulomatous disease and a major health problem in developing countries. About 1/3 of world's population is infected with mycobacterium tuberculosis.
A total of 1.5 million people died from TB in 2018 (including 251 000 people with HIV). Worldwide, TB is one of the top 10 causes of death and the leading cause from a single infectious agent (above HIV/AIDS).
An estimated 58 million lives were saved through TB diagnosis and treatment between 2000 and 2018.
                                        




   Classification of anti-tubercular drugs
                            

Rifampin, Isoniazid, Pyrazinamide, Ethambutol (RIPE) drugs are the first line drugs used for the treatment of TB.

                                  


ISONIAZID(H)

  • It acts on extracellular and intracellular tb (bacilli within macrophages).
  • It is active in acidic and alkaline medium

     MOA
 
                                                        INH(prodrug)
                                                                ↓
                                                 enters                                                                           mycobacteria
                                                                
                         catalase-peroxidase enzyme                              converts it into active form(Kat-G)
                                                               
                                                          active INH
                                                      ↙            ↘                                                
                   forms adduct with NAD     forms an                                                                         adduct                                                                            with                                                                                NADP                                           ↓                                                      ↓
   Inhibition of DHFRase             Inhibits InhA,                                                                 KasA genes 

                                 ↓                                     ↓                                      
                Inhibition  of  
DNA synthesis                                          Mycolic                                                                   acid                                                                 synthesis inhibited                                                     which are unique                                                           components of                                                           mycobacterial                                                                 cellwall                      
                                    


Adverse Effects
 
  • Peripheral neuritis, paresthesias, numbness, convulsions, mental disturbance.These effects are due to interference with production of active coenzyme pyridoxal phosphate from pyridoxine and its increased excretion through urine.
        Therefore pyridoxine is given 10mg/day prophylactically to prevent neurotoxicity.
         INH neurotoxicity is treated by pyridoxine 100mg/day.
  •  Another side effect is hepatotoxicity and INH must be stopped at the first sign of   hepatotoxicity.
  •  It may cause drug-induced lupus and anion gap metabolic acidosis.

      This drug penetrates the CNS freely and is a key chemotherapeutic agent in Tubercular Meningitis with proven potent bactericidal activity.


RIFAMPIN (R)

  1. It is a bactericidal drug. 
  2. Active against M.Leprae and  MAC(Mycobacterium Avium Complex).
  3. It affects extracellular and intracellular bacilli.

MOA
                                                           Rifampin
                                                                       ↓
                                binds to 𝛃-sub unit of DNA                                     dependant RNA polymerase
                                                                       ↓
                                            blockage of                                                            polymerization function
                                                                
                                                inhibition of DNA                                                            synthesis

Adverse Effects
  • Hepatitis:If jaundice develops then rifampin should be discontinued
  • cutaneous:flushing, pruritus, rash, redness
  • flu-like symptoms: chills, fever, headache, malaise, bone pain
  • nausea ,vomiting ,diarrhoea
 
Uses
  • Used in treatment of TB
  • Used in treatment of leprosy
  • Prophylaxis for meningococcal and H. influenzae meningitis
  • 2nd /3rd choice drug for MRSA

  ETHAMBUTOL (E)

  1.  Ethambutol blocks arabinosyl transferase, inhibiting carbohydrate formation at the cell wall.
  2. It is bacteriostatic. 
Adverse Effects
  •  optic neuritis (loss of visual acuity, red green color blindness).
  • hepatotoxicity is seen.

  PYRAZINAMIDE (Z)
 
  1. Pyrazinamide may cause hyperuricemia and needle shaped uric acid crystal formation. 
  2. It precipitate gout attacks. 
  3. can be hepatotoxic. 


                                                     
                                   
                        
                                                




Snippet from pathology:

2 comments:

  1. You are really getting polished day by day😁... Reallybwell written article... keep it up shishya!😛

    ReplyDelete

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