Introduction to drugs for tuberculosis and leprosy

1. Drugs for tuberculosis and
leprosy

2. Tuberculosis
• Tuberculosis (TB)is a chronic granulomatous disease
and a major health problem in developing countries.
About 1/3rd of the world’s population is infected with
mycobacterium tuberculosis.
• Anti-TB drugs can be divided into
– First line: These drugs have high antitubercular efficacy as
well as low toxicity; are used routinely.
– Second line: These drugs have either low antitubercular
efficacy or higher toxicity or both; and are used as reserve
drugs.

3. Antitubercular Drugs
• First line: Isoniazid (H), Rifampin (R), Pyrazinamide (Z),
Ethambutol (E), and Streptomycin (S)
• Second line: Thiacetazone (Tzn), Paraaminosalicylic acid
(PAS), Ethionamide (Etm), Cycloserine (Cys), Kanamycin
(Kmc), Amikacin (Am), Capreomycin (Cpr) and others.

4. Biology of tubercular infection
Ref: http://www.oxfordimmunotec.com/international/wp-content/uploads/sites/3/natural_history_TB.jpg

5. Goals of antitubercular chemotherapy
• Kill dividing bacilli: Drugs with early bactericidal action
rapidly reduce bacillary load in the patient and achieve
quick sputum negativity so that transmission of TB is
interrupted. This also affords quick symptom relief.
• Kill persisting bacilli: To effect cure and prevent
relapse. This depends on sterilizing capacity of the drug.
• Prevent emergence of resistance: The relative activity
of the first line drugs in achieving these goals.

6. Short Course Chemotherapy (DOTS)
• DOTS (directly observed treatment, short-course) is the
name given to the tuberculosis control strategy
recommended by the World Health Organization.
• In this patients are divided into 4 categories.
– Category I: New case of sputum smear positive or severe
pulmonary TB.
– Category II: Defaulted, irregularly treated and relapse cases.
– Category III: New sputum smear negative pulmonary TB.
– Category IV: Chronic cases who remained or again became
sputum smear positive after receiving fully supervised
category II treatment.

7. Short Course Chemotherapy (DOTS)
Category wise treatment regimens for tuberculosis

8. Multidrug-resistant (MDR) TB
• MDR-TB is defined as resistance to both H and R, and may be any
number of other (1st line) drug(s).
• The general principles of treatment of MDR-TB are:
– The regimen should have at least 4 drugs certain to be
effective
– Reliance about efficacy may be placed on survey of similar
patients who have been treated
– Avoid combining cross resistance drug
– Include drugs from group I to group IV (alternative
classification) in a hierarchial order

9. Tuberculosis in pregnant women
• The WHO and British Thoracic Society consider H, R, E and Z to
be safe to the foetus and recommend the standard 6 month
(2HRZE + 4HR) regimen for pregnant women with TB. S is
contraindicated because it is ototoxic to the foetus.
Isoniazid (H), Rifampin (R), Pyrazinamide (Z), Ethambutol (E)
Tuberculosis in AIDS patients
• The association of HIV and TB infection is a serious problem. HIV
positive cases have a higher incidence of extrapulmonary, more
severe, more lethal and more infectious TB.
• Initial intensive phase therapy with daily HRZE for 2 months is
started immediately on the diagnosis of TB, and is followed by a
continuation phase of HR for 4–7 months (total 6–9 months).

10. Leprosy
• Leprosy, also known as Hansen's disease
• It is a chronic infection caused by the bacteria
Mycobacterium leprae and Mycobacterium
lepromatosis.
• Antileprotic Drugs
Sulfone Dapsone (DDS)
Phenazine derivative Clofazimine
Antitubercular drugs Rifampin
Ethionamide
Other antibiotics Ofloxacin
Moxifloxacin
Minocycline
Clarithromycin

11. Treatment of leprosy
• Leprosy is a chronic granulomatous infection primarily
affecting skin, mucous membranes and nerves. It is
more prevalent among the lowest socioeconomic strata.
• Conventionally, all forms of leprosy had been treated
with dapsone alone (monotherapy: MT) 100–200 mg
daily, 5 days a week; duration of treatment depending
on the type: TT–4 to 5 years, LL–8 to 12 years or lifelong.

12. Multidrug therapy (MDT) of leprosy
• MDT is used to ‘treat dapsone resistant strains of M.
leprae’ and to ‘shorten the duration of treatment’.