Tuberculosis, also known as TB, is an airbone

infectious disease caused by Mycobacterium

tuberculosis that is preventable and curable. TB
usually affects the lungs, but can also affect other
parts of the body, such as the brain, the kidneys or
the spine. Only people who are sick with TB in their
lungs are infectious.
The general symptoms of TB disease include feelings of
sickness or weakness, weight loss, fever, and night sweats.
The symptoms of TB disease of the lungs also include
coughing, chest pain, and the coughing up of blood.
Diagnosis:

- Acid fast bacilli

- Chest x-ray
- - CT chest.
CHEMOTHERAPY FOR TUBERCULOSIS
M. tuberculosis is slow growing and requires treatment for
months to years. Latent TB infection can be treated for 9
months with isoniazid (INH) monotherapy or with 12 once-
weekly doses of INH (900 mg) and rifapentine
(900 mg).
In contrast, active TB disease must be treated with several
drugs. Treatment for drug-susceptible TB lasts for at least 6
months, while
treatment of multidrug-resistant TB (MDR-TB) typically lasts
for about 2 years.
Isoniazid
Isoniazid , along with rifampin, is one of the two most
important TB drugs.
1.Mechanism of action: Isoniazid is a prodrug Isoniazid
targets the enzymes acyl carrier protein reductase and β-
ketoacyl-ACP synthase (KasA), which are essential for the
synthesis of mycolic acid. Inhibiting mycolic acid leads to a
disruption in the bacterial cell wall.
Antibacterial spectrum: Isoniazid is specific for treatment of
M. tuberculosis. The drug is particularly effective against
rapidly growing bacilli and is also active against intracellular
organisms.
Resistance:
Resistance : mutation or overexpression of target enzyme.
Pharmacokinetics:
Isoniazid is readily absorbed after oral administration.
Absorption is impaired if isoniazid is taken with food,
particularly high-fat meals. The drug diffuses into all body
fluid and cells.
Excretion: is through glomerular filtration and secretion.
Adverse effects:
1.Hepatitis is the most serious adverse effect associated
with isoniazid.
2. Peripheral neuropathy.
3.Hypersensitivity reactions.
Rifampin:
Rifampin has broader antimicrobial activity than isoniazid
and can be used as part of treatment for several different
bacterial infections. Because resistant strains rapidly
emerge during monotherapy, it is never given as a single
agent in the treatment of active tuberculosis.
Mechanism of action:

Rifampin is thought to inhibit bacterial DNA-dependent RNA

polymerase, which appears to occur as a result of drug
binding in the polymerase subunit deep within the
DNA/RNA channel, facilitating direct blocking of the
elongating RNA.
Pharmacokinetics: Absorption is adequate after oral
administration. Distribution of rifampin occurs to all body
fluids and organs. Concentrations attained in the CSF are
variable, often 10% to 20% of blood concentrations.
Adverse effects:
Rifampin is generally well tolerated.
The most common adverse reactions include nausea,
vomiting, and rash. Hepatitis and death due to liver failure
are rare.
Drug interactions: Because rifampin induces a number of
phase I cytochrome P450 enzymes and phase II enzymes it
can decrease the half-lives of coadministered
drugs that are metabolized by these enzymes.
Pyrazinamide
Pyrazinamide is a synthetic, orally effective short course
agent used in combination with isoniazid, rifampin, and
ethambutol. The precise mechanism of action is unclear.
Liver toxicity is the most common side effect.
Ethambutol
Ethambutol is bacteriostatic and specific for
mycobacteria. Ethambutol inhibits arabinosyl transferase
which essential for mycobacterial cell wall synthesis.
Although its acts on cell wall its effect is bacteriostatic.
Ethambutol is used in combination with pyrazinamide,
isoniazid, and rifampin.
Optic neuritis is most famous side effect which can cause
vision loss.
Streptomycin: Streptomycin, an aminoglycoside
antibiotic, was one of the first effective agents for TB. Its
action appears to be greater against extracellular
organisms.
Infections due to streptomycin-resistant organisms may be
treated with kanamycin or amikacin, to which these bacilli
usually remain susceptible.