This is for educational purpose.

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)