Anti Tuberculosis Drugs

TUBERCULOSIS ?

Chronic granulomatous disease caused by Mycobacterium tuberculosis.

Tuberculosis typically attacks the lungs, but can also affect other parts of the body.

It is spread through the air when people who have an active TB infection cough, sneeze, or otherwise transmit respiratory fluids through the air.

Symptoms

Sites of extra-pulmonary tuberculosis

Chemotherapy of

tuberculosis

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Isoniazid Rifampicin Pyrazinamide Ethambutol Streptomycin

Ethionamide Thiacetazone Para Aminosalicylic acid (PAS) Amikacin Capreomycin Cycloserine Ciprofloxacin Kanamycin Rifabutin Rifapentine

Based

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Isoniazid Streptomycin Capromycin Ciprofloxacin Rifampicin Pyrazinamide Kanamycin

Ethambutol Thiacetazone PAS Ethionamide Cycloserine

Isoniazid (INH)

Most effective and cheapest primary anti tubercular drug.

Effective in both acidic and alkaline medium

Tuberculocidal for rapidly multiplying bacilli Tuberculostatic for resting bacilli

Mechanism of action Mycolic acids

synthesizes

Isoniazid inhibits

this synthesis

Adverse effects

Peripheral neuritis Hepatitis Psychosis Seizures Anorexia GIT discomfort Fever Allergic reactions

Less common

Rifampicin

Semisynthetic derivative of rifamycin , am anitibiotic obtained from streptomyces mediterranei.

Highly effective tuberculocidal Acts on both intra and extracellular organisms. It is called a sterilizing agent.

Mechanism of action

Rifampicin binds to beta subunit of DNA dependant RNA polymerase and inhibits RNA synthesis in bacteria.

It cannot bind to human RNA polymerase, thus selectively destroying the bacteria.

Adverse effects

Hepatotoxicity GIT disturbances Flu-like syndrome CNS symptoms – drowsiness, ataxia,

confusion, peripheral neuropathy etc Hypersensitivity reactions Staining of secretions

Uses

TB & atypical mycobacterial infections

Leprosy Prophylaxis

in H. influenza

Resistant staph

infections

Brucellosis

Pneumococcal meningitis

To eradicate carrier state

Pyrazinamide

Analog of nicotinamide Tuberculocidal Requires acidic pH for its activity Mechanism of action not clearly known. HEPATOTOXICITY is theMost common adverse effect

May inhibit

synthesis of mycolic

acids

Streptomycin

Tuberculocidal Acts only against extracellular

organisms Has to be given IM When used alone resistance develops. Least preferred first line drug.

Ethambutol

Tuberculostatic Also effective against atypical mycobacteria. Well absorbed on oral administration Dose should be reduced in renal failure Optic neuritis is an important adverse

effect which needs withdrawal of the drug. It decreases the renal excretion of uric

acid and enhances plasma urate levels.

Relative activity of first line drugs

INH: potent bactericidal Rifampicin: potent bactericidal

Pyrazinamide: weak bactericidal Ethambutol: bacteriostatic Streptomycin: bactericidal

Synergistic effect

NEVER USE A SINGLE DRUG FOR CHEMOTHERAPY IN TUBERCULOSIS, A

COMBINATION OF 2 OR MORE IS ALWAYS BETTER

Second line drugs in TB

Less effective More toxic Used only if organism is resistant to

first line drugs Ethionamide , PAS, cycloserine :

bacteriostatic Amikacin, capromycin,

fluoroquinolones are used in Multi Drug Resistant TB

Phases of chemotherapy

Phase I

• 1-3 months• Rapidly kills

bacilli• Symptomatic

relief

Phase II

• 4-6 months• Eliminates

remaining bacilli• Prevents relapse

Conventional drug regimen

1. INH+S+T daily for 2 months2. INH+T daily for 10 months

INH – isoniazidS – StreptomycinT - Thiacetazone

Short term regimans

1. INH+R+Z+E/S daily or thrice a week for 2 months followed by:

2. INH+R daily or thrice a week for 4 months

3. INH+R+Z trice a week for 2 months followed by

4. INH+R daily for 7 months.

TH

AN

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