Anti TB Cology

Prepared By:-
Meraj Khan
Assistant Professor
Sop, ITMBU
ANTIMYCOBACTERIUM DRUGS
The drugs used to treat pathogenesis or disease due to the mycobacteria
that is tuberculosis (TB), Mycobacterium avium-intracellulare infections, and
leprosy is known as Antimycobacterium drugs.
Disease Causative agent Therapy

Tuberculosis Mycobacterium Anti-tuberculosis drug
tuberculosis
Leprosy or Mycobacterium leprae Anti-Leprotic drugs
Hansen’s disease
Structure Mycobacteria
Classification of Anti-tuberculosis drugs:-
2. Macrolides:-
1. First line drugs:- Clarithromycin
Isoniazid Azithromycin
Ethambutol
Rifampin 3. Injectable(Aminoglycosides):-
Streptomycin Kanamycin
Pyrazinamide Amikacin
Capreomycin
2. Second line drugs:-
4. Other Oral drugs:-
1. Fluoroquinolones:- Thiacetazone
Ciprofloxacin Paraaminosalicylic acid
Ofloxacin Ethionamide
Levofloxacin Cycloserine
Moxifloxacin Rifabutin
MOA:-
Macrolides
Aminoglycosides
Protein Synthesis
Inhibitorss
All first line therapy are

bactericydal except Ethambutol
The goals of TB therapy:-
The goals of TB therapy are to kill tubercle bacilli rapidly, to eliminate persistent
bacilli and prevent relapse, and to prevent disease transmission.
Multidrug therapy for at least 6 months is required to eradicate the pathogen.

Because of the long duration of treatment and difficulties with patient adherence,
directly observed therapy (DOT), in which a health care provider observes each drug
administration to ensure adherence to the treatment regimen, is the Gold standard
treatment protocol.
Since the 1980s, the prevalence of multidrug-resistant TB (MDR-TB) and extensively

drug-resistant TB (XDRTB) has been increasing at an alarming rate.
MDR-TB is defined as resistance to at least isoniazid and rifampin
XDR-TB is defined as MDR-TB plus resistance to fluoroquinolones and at least one of

the injectable second-line drugs (amikacin, capreomycin, or kanamycin).
Isoniazid (H):-
It is a prodrug activated by catalase-peroxidase (coded by KatG). Active
metabolite inhibits the enzyme ketoenoylreductase (coded by inh A),
required for mycolic acid synthesis, an essential component of
mycobacterial cell wall. It acts by O2 dependent pathway such as catalase
peroxidase reaction.
Mycobacterial strains are assumed to be susceptible to isoniazid, if the
resistance is less than 4%.
It is bacteriostatic against resting and bactericidal against rapidly
multiplying organisms.
It is effective against intra- as well as extra-cellular mycobacteria.
Action is most marked against rapidly multiplying bacilli (less effective

against slow multipliers).
It is effective orally and metabolized by ACETYLATION which is genetically
controlled. Fast acetylators require high dose and slow acetylators are
predisposed to toxicity (particularly peripheral neuritis).
It is an essential component of multi-drug therapy of tuberculosis and is

drug of choice (used solely) for prophylaxis of tuberculosis and for
treatment of latent tuberculosis infection.
Resistance occurs due to mutation in Kat G (gene for catalse-peroxidase)

or inhA. Mutation in kat G is responsible for high level resistance whereas
mutation in inhA confers cross resistance to ethionamide.
ASVERSE EFFECT:-
It causes peripheral neuritis that can be prevented and treated by

pyridoxine.
It is also hepatotoxic and can cause hemolysis in G-6 PD deficient patients.
Isoniazid also inhibits MAO-A; thus can result in cheese reaction.
Rash, fever, anemia, optic atrophy, seizures, lupus like syndrome, psychosis
and gynaecomastia has also been reported with this drug.
Rifampicin (R)
It is a derivative of rifamycin (other derivatives are rifabutin and rifapentine). It is
bactericidal against both dividing and non-dividing mycobacterium and acts by
inhibiting DNA dependent RNA polymerase.
It undergoes enterohepatic circulation and is partly metabolized in the liver.
Metabolites are coloured and can cause orange discolouration of the urine.
Food interferes with absorption, therefore it must be given empty stomach.
It penetrates all membranes including blood brain and placental barrier.
It is equally effective against intra- and extra-cellular bacilli.
It is the only bactericidal drug active against dormant bacteria in solid caseous
lesions.
Apart from tuberculosis, it is also used in leprosy (to delay resistance to
dapsone). It is the most effective and fastest acting drug in leprosy.
It can also be used as a prophylactic drug for meningococcal and
staphylococcal carrier states.
Rifabutin has little chances of drug interactions and is equally effective, so it is used
in the treatment of tuberculosis in AIDS patients (getting antiretroviral drugs).
PAS delays absorption, therefore concomitant administration should be avoided.
Patient on warfarin therapy should be shifted to unfractionated heparin or

low molecular weight heparin, if rifampicin is being used for the treatment of
tuberculosis.
Adverse effect:-
It can cause light chain proteinuria and may impair antibody responses.
It is also hepatotoxic in nature and may cause skin rash, flu like syndrome
(more prominent with intermittent regimen) and anemia.
Rifampicin is an inducer of drug metabolizing enzymes and enhances the

metabolism of many drugs like anticonvulsants, oral contraceptives, oral
anticoagulants, antiretroviral drugs etc.
The female on oral contraceptives should either increase the dose of the pill
or use an alternative method of contraception, when using rifampicin as a
component of antitubercular treatment.
Fluoroquinolones:-
Antileprotic drugs
The drugs used for treatment of leprosy is called as Antileprotic drugs.
Classification of Antileprotic drugs:-

1. Sulfone:- Dapsone (DDS)
2. Phenazine derivative:- Clofazimine
3. Antitubercular drugs:- Rifampin, Ethionamide
4. Other antibiotics:- Ofloxacin, Minocycline, Clarithromycin
MECHANISM OF ACTION:-
sulfamethoxazole
Dapsone
It is a leprostatic drug related to sulfonamides with similar mechanism of
action.
It is metabolized by ACETYLATION and undergoes enterohepatic circulation.
It can cause gastrointestinal irritation, fever, skin rash, methemoglobinemia
and hemolysis in G-6-PD deficient patients.
Hemolytic anemia is the most common adverse effect of dapsone.
It can also cause sulfone (DDS) syndrome that is also called infectious
mononucleosis like syndrome.
ACEDAPSONE is a repository form of dapsone whose single intramuscular
injection maintains inhibitory levels of dapsone in tissues for up to 3 months.
Dapsone is also an alternative drug for the treatment of Pneumocystis
jiroveci infection in AIDS patients.
It is the drug of choice for treatment of dermatitis herpetiformis.
Clofazimine:-
It is a dye with leprostatic and anti-inflammatory activity.

It interferes with the template function of DNA.
It can cause gastrointestinal irritation, icthyosis of skin and discolouration of
skin and secretions.
Due to its anti-inflammatory action it can be used for lepra reaction.
Treatment of Leprosy:-
I. Pauci-bacillary leprosy:- It is the form of leprosy in which five or less

skin lesions are present and includes TT, BT and indeterminate leprosy.
The treatment is 600mg once monthly supervised dose of
rifampicin and 100mg daily dose of dapsone for 6 months.
II. Multi-bacillary leprosy:- It includes leprosy with more than five skin
lesions or smear positive cases even if the lesions are less than five. BB, BL
and LL leprosy are multi bacillary.
 The treatment is 600mg rifampicin + 300mg clofazimine (once monthly
supervised dose) and 100mg dapsone and 50mg clofazimine once daily
for one year.
 Another regimen called single lesion single dose therapy utilizes 600mg
rifampicin + 400mg ofloxacin + 100mg minocycline (ROM therapy) as a
single dose.

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Prepared By:-

Disease Causative agent Therapy

All first line therapy are

Multidrug therapy for at least 6 months is required to eradicate the pathogen.

Since the 1980s, the prevalence of multidrug-resistant TB (MDR-TB) and extensively

MDR-TB is defined as resistance to at least isoniazid and rifampin

XDR-TB is defined as MDR-TB plus resistance to fluoroquinolones and at least one of

Action is most marked against rapidly multiplying bacilli (less effective

It is an essential component of multi-drug therapy of tuberculosis and is

Resistance occurs due to mutation in Kat G (gene for catalse-peroxidase)

It causes peripheral neuritis that can be prevented and treated by

Isoniazid also inhibits MAO-A; thus can result in cheese reaction.

PAS delays absorption, therefore concomitant administration should be avoided.

Patient on warfarin therapy should be shifted to unfractionated heparin or

Rifampicin is an inducer of drug metabolizing enzymes and enhances the

The drugs used for treatment of leprosy is called as Antileprotic drugs.

Classification of Antileprotic drugs:-

It is a dye with leprostatic and anti-inflammatory activity.

I. Pauci-bacillary leprosy:- It is the form of leprosy in which five or less

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