Assignment:

Pharmacology

ANTIMYCOBACTERIAL DRUGS
PRESENTED BY: NAZRAH IRFAN
DPT 3RD YEAR
ROLL NO. 02
 INTRODUCTION
Mycobacteria:
• Mycobacteria are rod-shaped, aerobic bacteria that do not
form spores.
• These are called “acid-fast” bacilli
• Their cell walls contain mycolic acid, which gives the genus
its name.
Antimycobacterial Drugs:
Antimycobacterial drug is a type of drug used in
chemotherapy to treat mycobacterial infections.
Types:
Types include:
• Tuberculosis Treatment
• Leprosy treatment
 RISK FACTORS
The chemotherapy of infections caused by Mycobacterium
tuberculosis, M leprae and M avium-intracellulare is
complicated by numerous factors including:

1. Limited information about the mechanism of

antimycobacterial drug action.
2. The development of resistance.
3. The slow growth & intracellular location of mycobacteria.
4. Chronic nature of mycobacterial disease, which require
protracted drug treatment and is associated with drug
toxicity.
5. Patient compliance issues.
CLASSIFICATION
 DRUS FOR TUBERCULOSIS
• TB treatment includes four first-line drugs.
• Second-line drugs are typically less effective, more toxic
and less extensively studied.
• These are used for patients who cannot tolerate first-line
drugs or who are infected with resistant TB.
• The first line agents used for the treatment of tuberculosis
are:
1. Isoniazid (INH)
2. Rifampin
3. Ethambutol
4. Pyrazinamide
 ISONIAZID
Isoniazid(INH) is a structural congener of pyridoxine.
Mechanism of action:
Its mechanism of action involves the inhibition of the
synthesis of mycolic acids which are essential components of
mycobacterial cell wall.
• Resistance can emerge rapidly if the drug is used alone.
• High-level resistance is associated with mutation in katG
gene that codes for a catalase peroxidase involved in the
bio activation of INH.
• Low level resistance occur via deletion in the inhA gene.
• INH is bactericidal in action.
 ISONIAZID CONT.
Pharmakokinetics:
• Isoniazid is readily absorbed after oral administration.
• The drug diffuses into all body fluids, cells and caseous
material and penetrate to act on intracellular mycobacteria.
• The metabolism of INH is by acetylation and is under
genetic control. Patient maybe fast acetylator or slow
acetylator.
• INH half-life in fast acetylator is 60-90 min.
• INH half-life in slow acetylator is 3-4 hours
• Fast acetylators may require higher dosage than slow
acetylators for equivalent therapeutic effects.
 ISONIAZID CONT.
Adverse effects:
The adverse effects of Isoniazid are:
• Hepatitis: It can be fetal, increase with age and among
those who drink alcohol daily.
• Peripheral neuropathy: manifesting as parasthesia of hands
and feet appear to be due to a relative pyridoxine
deficiency.
• Central nervous system adverse effects can occur including
convulsions in patients prone to seizures.
• Hypersensitivity reactions with Isoniazid as rashes and
fever.
 ISONIAZID CONT.
Clinical Uses:

• INH is the single most important drug used

in tuberculosis and is a component of most
drug combination regimens.
• INH is given in the treatment of latent
infection (prophylaxis), including skin test
converters and for close contacts of patients
with active disease.
 RIFAMPIN
Rifampin, a derivative of rifamycin, is bactericidal against M
tuberculosis
Mechanism of action:
• The drug inhibits DNA-Dependant RNA polymerase in M
tuberculosis and many other microorganisms
• It is bactericidal for both intracellular and extracellular
mycobacteria
• It is effective against many gram positive and gram
negative organisms.
Other rifamycins:
• Rifabutin
• Rifapentine
 RIFAMPIN CONT.
Pharmacokinetics:
• Absorbtion is adequate after oral administration.
• Distribution of rifampin occur to all body fluids and organs.
• The drug undergoes enterohepatic cycling and is partially
metabolized in liver.
• Both free drug and metabolites are eliminated mainly in the
feces
 RIFAMPIN CONT.
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.
• There is modest increase in the incidence of hepatic
dysfunction when rifampin is coadministered with isoniazid
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.
 RIFAMPIN CONT.
Clinical Uses:
• In the treatment of tuberculosis, Rifampin is
almost always used in combination with
other drugs.
• Rifampin can be used as the sole drug in
treatment of latent tuberculosis in INH-
intolerant patients.
• Rifampin maybe used with vancomycin for
infections due to resistant staphylococci or
 ETHAMBUTOL
Ethambutol is bacteriostatic and specific for mycobacteria.
Mechanism of Action:
It inhibits arabinosyl transferase-an enzyme important for the
synthesis of mycobacterial cell wall.
• Ethambutol is used in combination with pyrazinamide,
isoniazid and rifampin pending culture and susceptibility
data.
Pharmacokinetics:
• Ethambutol is well distributed throughout the body.
• Penetration into CNS is minimal and it is questionably
adequate for tuberculous meningitis
• Both the parent drug and metabolites are primarily excreted
 ETHAMBUTOL CONT.
Adverse effects:
• The most important adverse effect is Optic neuritis, which
results in diminished visual acuity and loss of ability to
discriminate between red and green.
• The risk of optic neuritis increase with higher doses and in
patients with renal impairment.
• Uric acid excretion is decreased by ethambutol, and caution
should be exercised in patients with gout.
 ETHAMBUTOL CONT.

Clinical Uses:

The main use of Ehambutol is in

tuberculosis, and it is always given in
combination with other drugs.
 PYRAZINAMIDE
Pyrazinamide is a synthetic, orally effective short course
agent used in combination with isoniazid, rifampin and
ethambutol

• The precise mechanism of action of pyrazinamide is un clear.

• Pyrazinamide must be enzymatically hydrolyzed by
pyrazinamydase to pyrazinoic acid, which is the active form
of the drug.
• Some resistant strains lack the pyrazinamidase enzyme.
• Pyrazinamide is active against tuberculosis bacilli in acidic
lesions and in macrophages.
 PYRAZINAMIDE CONT.
Pharmacokinetics:
The drug distributes throughout the body,penetrating the CSF.
Adverse effects:
• Pyrazinamide may contribute liver toxicity.
• Uric acid retention is common but rarely precipitates a
gouty attack.

This drug is usually discontinued after 2 month of a 6 month

regimen.
Clinical Uses:
The combined use of Pyrazinamide with other antituberculous
drugs is an important factor in the success of short course