1. CHEMOTHERAPY OF LEPROSY

2. EPIDEMIOLOGY OF LEPROSY
• Leprosy is a chronic granulomatous infection
• Agent
– Mycobacterium Leprae -1873-Armauer
• Large number of person may be infected but
only few suffer chemically
• Source of Infection
– Nasal secretion
– Discharged from superficial ulcers

3. Clinical Manifestation
Cardinal features…
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–
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Hypo pigmented patches (T)
Loss of coetaneous sensation in affected areas.
Thickened nerves
M. Leprae in skin or nasal passage.
Signs of advanced disease…
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–
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Nodules / lumps in skin of face & ears.
Planter ulcers
Loss of fingers / toes
Nasal depression
Foot drop
Claw hand and toes.

4. BACTERIOLOGICAL CLASSIFICATION
PAUCIBACILLARY
MULTIBACILLARY
• NON INFECTIOUS
• INFECTIOUS
• TUBERCULOID
• LEPROMATOUS
• Incubation period 2-5yr
• Incubation period 8-12y
• < 5 LESIONS
• NORMAL CMI/ partially deficient
• +ve LEPROMIN
• FEW BACILLI
• > 5 LESIONS
• DEFICIENT CMI
• -ve LEPROMIN
• NUMEROUS BACILLI

5. Classification of Leprosy
– Indeterminate Type/Borderline Type
– Which ultimately progresses to either
tuberculoid or lepromatous

6. ANTILEPROTIC DRUGS
– SULFONE
:
DAPSONE, SULFOXONE, ACEDAPSONE
– PHENAZINE
:
CLOFAZIMINE
– ANTITUBERCULAR
:
RIFAMPIN
– ANTIBIOTICS
:
FQ: OFLOXACIN
Tetra: MINOCYCLIN
Macrolids: CLARITHROMYCIN

7. DAPSONE
– Diamino Diphenyl Sulfone (DDS) -1940
– Oldest, cheapest, most active, most commonly used
MOA :
Inhibition of PABA
Inhibit Bacterial Folic Acid Synthesis
Leprostatic
RESISTANCE : 1964
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More in lepromatous leprosy patients if used monotherapy
Primary- harbouring from resistant bacilli
Secondary- during treatment
Combined with Rifampicin

8. Pharmacokinetics of DAPSONE
– p. o. absorbed
– Distributed to all body compartment
– Retains in skin & organs upto 3 wks.
– Metabolised by
– acetylation
– glucuronid conjugation
– half life > 24 hrs.
– Dose is cumulative
– excretion through kidney (1-2 wks)

9. ADVERSE EFFECTS OF DAPSONE
– HAEMOLYTIC ANAEMIA
– METHAEMOGLOBINEMIA
– GASTRIC INTOLERANCE –decrease later
– CUTANEOUS REACTIONS
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ALLERGIC RASHES
FIXED DRUG ERUPTION
HYPERMELANOSIS
PHOTOTOXICITY
– LEPRA REACTIONS
– SULFONE SYNDROME

10. ADVERSE EFFECTS OF DAPSONE
Type 2
Type 1
• Delayed hypersensitivity
• Erythema nodosum leprosum
• IV
• Humoral antibody response
• Reversal reaction
•
Reactions to M. Leprae antigens
• Characterized by cutanoeus
ulceration, multiple nerve
involvement
• Prevented by corticosteroids
•
III
•
Response to dead bacteria
• Characterized lesions enlarge,
become red, inflamed, painful
• Treated by
clofazamine/corticosteriods

11. SULFONE SYNDROME
• If lepra reactions develops after 1-2months c/s sulfone syndrome
• Characterized by
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Fever
Lymphnode enlargement
general malaise
Jaundice
anaemia

12. INDICATIONS OF DAPSONE
– WELL TOLERATED
– CHEAP
– TABLET : 100 mg OD
– I.M. DEPOT : Acedapsone
– BOTH TYPE OF LEPROSY
– CI in Hb% below 7g
– OTHER –
– PNEUMOCYSTIS CARINII PNEUMONIA(100mg)
– DERMATITIS HERPETIFORMIS (first 50mg, slow 300mg)

13. CLOFAZIMINE
• MOA :
– BINDS TO DNA 
 INTERFERES TEMPLATE FUNCTION of DNA
 INHIBITS GROWTH
– LEPROSTATIC
– ANTI-INFLAMMATORY

14. KINETICS OF CLOFAZIMINE
– P. O. INCOMPLETE ABSORPTION
– WIDELY DISTRIBUTED IN TISSUES : PHAGOCYTES
– HALF LIFE : 60 – 70 hrs.
– Elimination through FAECES

15. ADVERSE EFFECTS OF CLOFAZIMINE
– REDDISH-BROWN DISCOLORATION
• SKIN ; HAIR ; SECRETIONS
– CONJUNCTIVAL PIGMENTATION
– ACNEFORM ERRUPTIONS
– PHOTOTOXICITY
– GASTRIC INTOLERANCE
• ABDOMINAL PAIN
• LOOSE STOOL
PRECAUTION
:
PREGNANCY/Liver/Kidney damage

16. INDICATIONS OF CLOFAZIMINE
– DAPSONE RESISTANT LEPROSY
– PREFERED IN MDT OF LEPROSY
– LEPRA REACTION
– ULCERATIVE LESIONS : M. ulcerans

17. RIFAMPIN
– INHIBIT DNA DEPENDENT RNA SYNTHESIS
– BACTERIOCIDAL
– KILLS 99.9 % M. leprae : NONCONTAGIOUS
– RESISTANCE : MONOTHERAPY
– USE IN MDT :
DURATION OF T/t
– DOSE 600 mg MONTHLY

18. OFLOXACIN
– KILLS 99.9 % BACILLI
: 22 Day MONOTHERAPY
– HASTEN BACTERIOLOGICAL & CLINICAL RESPONSE
– SHORTEN DURATION OF THERAPY
– ALTERNATIVE DRUG
– RIFAMPIN INTOLERANCE / RESISTANCE
– DOSE : 400 mg/day

19. CLARITHROMYCIN
– MACROLIDE ANTIBIOTIC
– BACTERICIDAL < RIFAMPIN
– KILLS 99.9 % BACILLI IN 8 wks
– DOSE : 500 mg/day
– ALTERNATIVE DRUG

20. MINOCYCLINE
– TETRACYCLIN
– RIFAMPIN > MINOCYCLINE >
CLARITHROMYCIN
– ALTERNATIVE TO CLOFAZIMINE
– DOSE : 100 mg/day

21. WHO REGIMEN
• PAUCIBACILLARY LEPROSY
DAPSONE
RIFAMPIN
100 mg OD
600 mg MONTHLY
DURATION
6 MONTHS
• MULTIBACILLARY LEPROSY
DAPSONE
100 mg OD
RIFAMPIN
600 mg MONTHLY
CLOFAZIMINE 300 mg MONTHLY
50 mg DAILY
DURATION
2 YEARS