Antitubercular

Drugs
 Tuberculosis (TB)
• Tuberculosis (TB) is an infectious disease usually caused by Mycobacterium
tuberculosis (MTB) bacteria. Tuberculosis generally affects the lungs, but
can also affect other parts of the body.
•  Most infections show no symptoms, in which case it is known as latent
tuberculosis. About 10% of latent infections progress to active disease
which, if left untreated, kills about half of those affected. The classic
symptoms of active TB are a chronic cough with blood-
containing mucus, fever, night sweats, and weight loss. It was historically
called "consumption" due to the weight loss. Infection of other organs can
cause a wide range of symptoms.
Tuberculosis is spread through the air when people who have
active TB in their lungs cough, spit, speak, or sneeze.
 People with latent TB do not spread the disease.
 Active infection occurs more often in
people with HIV/AIDS and in those who smoke.
 Diagnosis of active TB is based
on chest X-rays, as well as microscopic
 examination and culture of body fluids. 
Diagnosis of latent TB relies on the tuberculin
skin test (TST) or blood tests.
• Prevention of TB involves screening those at high risk, early detection
and treatment of cases, and vaccination with the bacillus Calmette-
Guérin (BCG) vaccine.
• Signs and symptoms
• Tuberculosis may infect any part of the body, but most commonly
occurs in the lungs (known as pulmonary
tuberculosis). Extrapulmonary TB occurs when tuberculosis develops
outside of the lungs, although extrapulmonary TB may coexist with
pulmonary TB.
• General signs and symptoms include fever, chills, night sweats, loss of
appetite, weight loss, and fatigue.
•  Significant nail clubbing may also occur.
 Causes
• The main cause of TB is Mycobacterium tuberculosis (MTB), a small, aerobic, nonmotile  bacillus
.
The high lipid content of this pathogen accounts
for many of its unique clinical characteristics.
•  It divides every 16 to 20 hours, which is an extremely
slow rate compared with other bacteria, which usually divide in less than
an hour Mycobacteria have an outer membranelipid bilayer.
If a Gram stain is performed, MTB either stains
very weakly "Gram-positive" or does not retain dye
as a result of the high lipid and mycolic acid content
of its cell wall.MTB can withstand weak disinfectants and survive in a dry state for weeks.
In nature, the bacterium can grow only within the cells of a
 host organism, but M. tuberculosis can be cultured in the laboratory.
 Drug regimes for TB:
• The First line;
• Of the approved drugs, the first-line anti-TB agents that form the core
of treatment regimens are:
1. Streptomycin
2. isoniazid (INH)
3. rifampin (RIF)
4. ethambutol (EMB)
5. pyrazinamide (PZA)
 Streptomycin
• It was the first antibiotic discovered that was effective against TB.
• Today it is no longer considered as a first line drug because of high
rates of resistance.
 Isoniazid (INH)
• Isoniazid is often used to treat latent and active tuberculosis infections.
In persons with isoniazid-sensitive Mycobacterium
tuberculosis infection, drug regimens based on isoniazid are usually
effective when persons adhere to the prescribed treatment.
• However, in persons with isoniazid-resistant Mycobacterium
tuberculosis infection, drug regimens based on isoniazid have a high
rate of failure.
MOA:
• Isoniazid is a prodrug that inhibits the formation
of the mycobacterial cell wall.
Pharmacokinetics
• It is well absorbed from the GI tract
• Well distributed in body tissue and cross BBB
• Largely excreted in urin ,metabolized in liver
• Dose:300mg /day
S/E:
Common side effects include poor coordination, poor appetite, nausea,
numbness, and feeling tired. More severe side effects include 
liver problems. Use is generally not recommended in children. It is
unclear if use is safe in pregnancy.
 Ethambutol (EMB)
• Ethambutol is a medication primarily used to treat tuberculosis. It is usually
given in combination with other tuberculosis medications, such as isoniazid,
rifampicin and pyrazinamide. It may also be used to treat Mycobacterium
avium complex, and Mycobacterium kansasii. It is taken by mouth.
MOA:
Ethambutol is bacteriostatic against actively growing TB bacilli.
It works by obstructing the formation of cell wall
Pharmacokinetics:
It is well absorbed from the gastrointestinal tract and well distributed in body
tissues and fluids.
50% is excreted unchanged in urine.
Adverse effect
The most serious adverse effect is retrobulbar neuritis, which appears to be dose
related and manifests with blurred vision, central scotoma, and red-green
color blindness. At the standard daily dose of 20 mg/kg.
Other side effects include liver problems and allergic reactions .
It is not recommended in people with optic neuritis
significant kidney problems, or under the age of sex.
 pyrazinamide (PZA)
• Pyrazinamide is a medication used to treat tuberculosis. For active
tuberculosis, it is often used with rifampicin, isoniazid, and
either streptomycin or ethambutol. 
• It is not generally recommended for the treatment of latent tuberculosis .
• It is taken by mouth.
Pharmacokinetics:
Pyrazinamide is well absorbed orally. It crosses inflamed meninges and is an
essential part of the treatment of tuberculous meningitis.
It is metabolised by the liver and the metabolic
products are excreted by the kidneys.
MOA
• Pyrazinamide is a prodrug that stops the growth of M. tuberculosis.

Side Effect
• common side effects include nausea, loss of appetite, muscle and joint pains,
and rash.
• More serious side effects include gout, liver toxicity, and sensitivity to
sunlight.
• It is not recommended in those with significant
liver disease or porphyria.
• Elimination half-life: 9 to 10 hours
 Rifampin (RIF)
• Rifampicin, also known as rifampin, is an antibiotic used to treat several types
of bacterial infections, including tuberculosis
Mycobacteriumtuberculosis It is almost always used together with other
antibiotics such as pyrazinamide, isoniazid, and ethambutol.
 For the treatment of tuberculosis, it is administered daily for at least 6 months.
MOA:
Rifampicin inhibits bacterial DNA-dependent RNA synthesis by inhibiting bacterial
DNA-dependent RNA polymerase.

Binding of rifampicin in the active site

of RNA polymerase. Mutation of amino acids shown in red
are involved in resistance to the antibiotic.
 Pharmacokinetics:
• Orally administered rifampicin results in peak plasma concentrations in about 2–4 hours.

Adverse effect:
The most serious adverse effect is hepatotoxicity.
and people receiving it often undergo baseline and frequent 
liver function tests to detect early liver damage
The more common side effects include fever,
gastrointestinal disturbances, rashes, and immunological
reactions.
Taking rifampicin usually causes certain bodily fluids, such as urine,
sweat, and tears, to become orange-red in color.
• The Second Line;
• The second line drugs (WHO groups 2, 3 and 4) are only used to treat disease that is resistant to first
line therapy (i.e., for extensively drug-resistant tuberculosis (XDR-TB) or multidrug-resistant
tuberculosis (MDR-TB)).A drug may be classed as second-line instead of first-line for one of three
possible reasons: it may be less effective than the first-line drugs (e.g., p- aminosalicylic acid); or, it
may have toxic side-effects (e.g., cycloserine); or it may be effective, but unavailable in many
developing countries (e.g., fluoroquinolones):
• aminoglycosides (WHO group 2): e.g., amikacin (AMK), kanamycin (KM);
• polypeptides(WHO group 2): e.g., capreomycin, viomycin, enviomycin;
• fluoroquinolones (WHO group 3): e.g., ciprofloxacin (CIP), levofloxacin, moxifloxacin (MXF);
• thioamides (WHO group 4): e.g. ethionamide, prothionamide
• cycloserine (WHO group 4)
• terizidone (WHO group 5)
 Rifabutin(RFb)

• Rifabutin (Rfb) is an antibiotic used to treat tuberculosis and prevent

and treat Mycobacterium avium complex.
•  It is typically only used in those who cannot tolerate rifampin such as
people with HIV/AIDS on antiretrovirals.
• For active tuberculosis it is used with other antimycobacterial
medications. For latent tuberculosis it may be used by itself when the
exposure was with drug-resistant TB.
• Metabolism :liver
• Elimination half-life:28 to 62 hours
• Excretion:kidney and fecal
 Ethionamide
• Ethionamide is an antibiotic used to treat tuberculosis.
•  Specifically it is used, along with other antituberculosis medications,
to treat active multidrug-resistant tuberculosis.
• The mechanism of action is thought to be
through disruption of mycolic acid.
• It crosses the blood brain barrier.
• Common side effects include nausea, diarrhea, abdominal pain, and
loss of appetite.
• Serious side effects may include liver inflammation and depression
 Capreomycin

• Capreomycin is an antibiotic which is given in combination with

other antibiotics for the treatment of tuberculosis.
•  Specifically it is a second line treatment used for active 
drug resistant tuberculosis.
•  It is given by injection into a vein or muscle.
• Side effects : hypokalemia, renal toxicity
and ototoxicity.
 Cycloserine
• Cycloserine works as an antibiotic by inhibiting cell-wall biosynthesis in
bacteria.
• Common side effects include allergic reactions, seizures, sleepiness,
unsteadiness, and numbness.
• Most serious toxic effect peripheral neuritis,CNS effect
• Metabolism:liver
• Elimination half-life:10 hrs (normal kidney function)
• Excretion:kidney
 Amikacin

• Amikacin is not absorbed orally and thus must be administered

parenterally.
• Side-effects of amikacin are similar to those of other
aminoglycosides. Kidney damage and ototoxicity.
• Metabolism : Mostly unmetabolized
• Elimination half-life: 2–3 hour
• Excretion: kidney