Anusha Shaji discusses several drugs used to treat leprosy, including dapsone, clofazimine, rifampin, and ethionamide. Dapsone inhibits folic acid synthesis in Mycobacterium leprae. Clofazimine binds to DNA and generates toxic oxygen radicals. Rifampin is bactericidal and renders patients noncontagious within a week. However, resistance can develop with rifampin alone. Ethionamide has antileprotic activity but causes hepatotoxicity in 10% of patients. Ofloxacin is also highly active against M. leprae.

1. ANTILEPROTIC
DRUGS
Anusha Shaji, B.Pharm, M.Pharm
Assistant Professor
Department of Pharmacology
Nirmala College of Pharmacy,
Muvattupuzha, Ernakulam

2. ANTILEPROTIC DRUGS
Leprosy, caused by Mycobacterium
leprae
Strongly acid-fast rod-shaped
Also known as Hansen's disease,
after the scientist who discovered M.
leprae in 1873
Long incubation period (3 – 5 years)
Primarily affect superficial tissues,
especially the skin and peripheral
nerves.

3. A leprosy patient is someone
who: has a skin patch or patches
with a definite loss of sensation
Leprosy patches
Can be pale or reddish or
copper-coloured;
Can be flat or raised
Do not itch
Usually do not hurt
Lack sensation to heat, touch or
pain
Can appear anywhere.

4. Leprosy manifests in several clinical forms
The most widely used classification of leprosy is that of Ridley
and Jopling (1996) who divided leprosy into two polar types;

5. CLASSIFICATION

6. Dapsone
Dapsone is structurally related to the sulfonamides and has the
same mechanism of action, i.e. inhibition of PABA incorporation into
folic acid
Its antibacterial action is antagonized by PABA.
It is leprostatic at low concentrations, and at relatively higher
concentrations arrests the growth of many other bacteria sensitive to
sulfonamides.
Specificity for M. leprae may be due to difference in the affinity of its
folate synthase.
Dapsone is also employed in the treatment of pneumonia caused
by Pneumocystis jiroveci in patients infected with HIV.

7. Pharmacokinetics
The drug is well absorbed from the gastrointestinal tract
Distributed throughout the body
The parent drug enters the enterohepatic circulation and
undergoes hepatic acetylation.
Both parent drug and metabolites are eliminated through the
urine.
Adverse reactions
Hemolysis, especially in patients with glucose 6-phosphate
dehydrogenase defi ciency, as well as methemoglobinemia, Peripheral
neuropathy, and the possibility of developing erythema nodosum
leprosum (a serious and severe skin complication of leprosy).

8. Clofazimine
Clofazimine is a phenazine dye that binds to DNA and prevents it
from serving as a template for future DNA replication.
Its redox properties may lead to the generation of cytotoxic oxygen
radicals that are also toxic to the bacteria.
Clofazimine is bactericidal to M. leprae and has some activity
against M. avium-intracellulare complex.
Following oral absorption, the drug accumulates in tissues,
allowing intermittent therapy, but it does not enter the CNS.
Patients may develop a red-brown discoloration of the skin.
Eosinophilic enteritis has been reported as an adverse effect.
The drug also has some anti-inflammatory activity; thus, erythema
nodosum leprosum does not develop.

9. Rifampin (R)
It is an important antitubercular drug
Also bactericidal to M. leprae; rapidly renders leprosy patients
noncontagious.
Up to 99.99% M. leprae are killed in 3–7 days.
However, it is not satisfactory if used alone
Some bacilli persist even after prolonged treatment-resistance
develops.
It has been included in the multidrug therapy of leprosy: shortens
duration of treatment.
The 600 mg monthly dose used in leprosy is relatively nontoxic and
does not induce metabolism of other drugs.

10. It should not be given to patients with hepatic or renal
dysfunction.
The rifampin congener rifabutin is also cidal against M. leprae,
but not superior to rifampin.
Ethionamide
This antitubercular drug has significant antileprotic activity
But causes hepatotoxicity in ~ 10% patients.
It has been used as an alternative to clofazimine, but other
substitutes are preferred.
It should be used (250 mg/day) only when absolutely necessary

11. Other Antibiotics
Ciprofloxacin is not active against M. leprae, but ofloxacin,
pefloxacin, gatifloxacin and sparfloxacin are highly active.
Ofloxacin
Many trials have evaluated ofloxacin as a component of MDT and
found it to hasten the bacteriological and clinical response.
Over 99.9% bacilli were found to be killed by 22 daily doses of
ofloxacin monotherapy.
However, it is not included in the standard treatment protocols, but
can be used in alternative regimens in case rifampin cannot be used, or
to shorten the duration of treatment.
Dose: 400 mg/day.