Chemotherapy of Tuberculosis and Leprosy

TUBERCULOSIS

Tuberculosis is a chronic granulomatous disease caused by Mycobacterium tuberculosis, in

developing countries, it is major public health, problem;

Drugs used in tuberculosis

1 first line drugs

•Isoniazid, rifampicin. Pyrazinamide, ethambutol, Streptomycin

2.Second line drugs

•Ethionamide, thiacetazone para-amino salicylic acid (PAC), amikacin, ciprofloxacin,

capreomycin,cycloserine, rifabugin, kanamycin,

Based in anti tubercular activity, drugs may be grouped as :

1. Tuberculocidal agents
• Isoniazid, ritrampicin, streptomycin, pyrazinamide, capriomycin, kanamycin, cyprofloxacin
2. Tuberculostatic agentss
•ethambutol, ethionamide, thiacetazone, cycloserine, PAS
I. First line drugs
1) Isoniazide
Isoniazid is the most effective and cheapest primary anti tubercular drug.

It destroys:

 Intracellilar bacilli as it penetrates into the cells , that is tubercle bacilli in macrophages.
 Bacilli multiply in the walls of the cavities.
  Thus it is effective against both intra and extra cellilar organisms.if used alone , mycobacteri
develop resistence to it. Hence it should be used combination with kther drugs.
 Mechanism of action: it inhibits the synthesis of mycolic acids which are important componrnts
of the mycobacterium cell wall.
 Pharmacockynetics: it is completely absorbed orally, penetrates all tissues , tubercular activities,
necrotic tissues and CSE.
 Adverse effect

Isoniazid can cause peripheral neurits because it interferes with utilization and increases the
excretion of pyridoxine.this can be avoided by giving prophylactic pyridoxin with
isoniazide.Hepatitis is another major adverse effect ,more common in alcoholistic.It can affect
CNS toxicity including psychosis and sezures but are common.

2) Rifampicin
Rifampicin is a semisynthetic derivative of rifamycin , an antibiotic obtained from streptomyces
mediteraneil. The other rifamycin are rifabutun and rifapentine. Rifampicin is bactericidal to M.
tuberculosis, M. leprose and atypical mycobacteria. It also inhibits most gram-positive and gram
negative bacteria like Steph aureus N meningitidis. E coli,proteus and Legranella

 Antitubercular action : Rifampicin is highly effective, tuberculocidal and is the only drug
that acts on persisters; acts on both intra and extracellular organisms and is effective
against tubercle bacilli resistant to other drugs.
 Mechanism of action : Rifampicin binds to DNA dependent RNA polymerase and
inhibits RNA synthesis in the bacteria.
 Pharmacokinetics : Rifampicin is well- absorbed and has good tissue penetrability-
reaches caseous material, cavities and CSF appears in saliva, tears and sweat.
 Adverse Effects:
Rifampicin is well tolerated. Skin rashes, diarrhea, nephritis and hepatotoxicity .It can
occur in intermittent dosing regiment ,a flu like syndrome can occur. The secretions including
tears, sale and sweat become orange,red and the patient should be informed about this.

 Uses
▪︎Tuberculosis and atypical mycobacterial infections.
▪︎Leprosy
▪︎Prophylaxis of H.influensae and meningococcal meningitis in close contacts particularly
in children 20mg/kg/day for 4 days
▪︎Resistant staphylococcal infections.
▪︎To irradicate carrier state
 3) Rifabutin
Rifabutin is similar to rifampicin except that it causes milder enzyme induction and is more
active against atypial mobacteria. Rifabutin may be used In place of rifampicin in tuberculosis
patients with AIDS who are receiving anti retro viral drugs. These antii viral drugs are also
metabolised by microsomal enzyme and rifampicin being a powerful enzyme induce can result
in many drug interactions.

4) Rifapentine
Rifapentine is an analog of rifampicin and is similar to rifampicin.

5) Pyrazinamide
Pyrazinamide is tuberculocidal and is more active in acidic pH. Mechanism of action is not
known. It is effective against intracellular bacilli.It used alone resistance develops. It is well
absorbed. Hepatotoxicity is the most common adverse effect

6) Streptomycin
It is tuberculocidal, acts only against extracellular organisms due to poor penetrating power. It
has to be given IM. When used alone resistance develops. Because of these disadvantages and
its toxicity, streptomycin is the least preferred of the first line drugs.

7) Ethambutol
Ethambutol is tuberculostatic and acts on test multiplying bacilli in the cavities. It is also
effective against atypical mycobacteria. It inhibits the incorporation of mycolic acids into the
mycobacterial cell wall.

II . Second line Drugs

1) Thiacetazone
Thiacetazone is tuberculostatic with low efficiency. It delays the development of resistance to
other drugs and its low cost makes it a suitable drug in combination regiments. Hepatotoxicity
dermatitis ,allergic reactions and GI side effects may occur.
 2) Ethionamide
This tuberculostatic drug is effective against both intra and extracellular organisms.It is also
effective in atypical mycobacteria.
Anorexia, nausea, vomiting and metallic tests in the mouth are the most common adverse
effects .It can also cause hepatitis, skin rashes and peripheral neuritis.

3) Para-aminosalicylic acid (PAS)

It is related to sulfonamides in tuberculostatic. Gastrointestinal effects like nausea, anorexia,
epigastric pain and diarrhea make it a poorly tolerated drug. Allergic reactions and hepatitis are
also seen. It is rarely used.
Other Second Line Drugs:

● Amikacin, kanamycin and capromycin

These are second line drugs that need parenteral administration. They are ototoxic and nephro
toxic and are used only in resistant cases. Amikacin is also effective against atypical
micobacteria.

● Cyclosenine

It is an antibiotic that inhibits cell wall synthesis is tuberculostatic and is also effective against
some gram-positive organisms. It causes CNS toxicity including headache, tremors,psychosis
and sometimes setures. It is only in resistant tuberculosis.

● Fluoroquinolones

Ciprofloxacin, ofloxacin and sparfloxacin inhibit tubercle bacilli and atypical mycobacteria. They
are useful in multi-drug resistant tuberculosis in combination with other drugs.

Treatment of Tuberculosis

Tuberculosis is one of the most difficult infections to cure. The properties of the mycobacteria
like slow division, development of resistance, ability