This document discusses drugs used to treat leprosy, also known as Hansen's disease. It is caused by Mycobacterium leprae bacteria. The main drugs discussed are: 1. Dapsone, the oldest and most commonly used drug. It works by inhibiting folic acid synthesis. It is effective but can cause anaemia or sulfone syndrome side effects. 2. Clofazimine, which has anti-inflammatory and antibacterial properties through various mechanisms of action. It accumulates in tissues and has a long half-life allowing intermittent dosing. Side effects include skin discoloration. 3. Other drugs mentioned are rifampin, ofloxacin, min

1. Unit III: Chemotherapy
b. Antileprotic agents
Presented by: Mirza Anwar Baig
M.Pharm (Pharmacology)
Anjuman I Islam's Kalsekar Technical Campus,
School of Pharmacy.
New Panvel,Navi Mumbai

2. What is Leprosy?
• Leprosy, caused by Mycobacterium leprae, has been considered incurable since
ages and bears a social stigma.
• Now, it is entirely curable, but deformities/defects already incurred may not
reverse.
CLASSIFICATION:
1. Sulfone
Dapsone (DDS)
2. Phenazine derivative
Clofazimine
3. Antitubercular drugs
Rifampin,
Ethionamide
4. Other antibiotics
Ofloxacin,
Moxifloxacin,
Minocycline,
Clarithromycin

3. Dapsone (DDS):
• It is diamino diphenyl sulfone (DDS)
• Simplest, oldest, cheapest, most active and most commonly used member of its
class.
Activity and mechanism
• Dapsone is chemically related to sulfonamides and has the same MoA
(inhibition of PABA incorporation into folic acid by folate synthase).
• The antibacterial action of dapsone is antagonized by PABA.
• It is leprostatic.
• Specificity for M. leprae may be due to difference in the affinity of its
folate synthase.
• Dapsone resistant M. leprae have mutated folate synthase which has lower
affinity for dapsone.

4. Compiled by: Prof.Anwar Baig (AIKTC,SOP) 4

5. Pharmacokinetics:
• Completely orally absorbed, widely distributed in the body, CSF penetration
is poor.
• 70% plasma protein bound, concentrated in skin, muscle, liver and kidney.
• Acetylated as well as glucuronide and sulfate conjugated in liver.
• Excretion occurs mostly in urine.
• Plasma t½ often > 24 hrs.
• Elimination takes 1–2 weeks or longer.

6. Adverse effects:
• Mild haemolytic anaemia
• Gastric intolerance
• Sulfone syndrome
It is the reaction which develops 4–6 weeks after starting dapsone
treatment: consists of fever, malaise, lymph node enlargement,
desquamation of skin, jaundice and anaemia.
Contraindications:
Dapsone should not be used in patients with severe anaemia (Hb < 7 g/dl),
G-6-PD deficiency and in those showing hypersensitivity reactions.

7. Clofazimine (Clo):
• It is a dye with leprostatic and antiinflammatory properties.
Mechanisms of action are:
• Interference with template function of DNA in M.leprae.
• Alteration of membrane structure and its transport function.
• Disruption of mitochondrial electron transport chain.
• Clinical response to clofazimine is slower than that to dapsone, and
resistance develops in 1–3 years.
• Orally active (40–70% absorbed).
• Accumulates in macrophages and gets deposited in many tissues including
subcutaneous fat, as needle-shaped crystals.
• Entry in CSF is poor.
• t½ is 70 days so that intermittent therapy is possible.

8. Adverse effects:
Skin :
• Reddish-black discolouration of skin
• Discolouration of hair and body secretions
• Dryness of skin
• Phototoxicity.
• Conjunctival pigmentation may create cosmetic problem.
GI symptoms:
• Nausea, anorexia, abdominal pain, weight loss and enteritis with
intermittent loose stools can occur
• Deposition of clofazimine crystals in the intestinal submucosa.
• Avoided during early pregnancy and in patients with liver or kidney
damage.

9. Other drugs:
• Rifampin (R)
• Ofloxacin (fluoroquinolones)
• Minocycline (tetracycline)
• Clarithromycin (macrolide antibiotic)