The document outlines the classification, mechanisms of action, pharmacokinetics, adverse effects, and treatment strategies for anti-leprosy drugs, including dapsone, clofazimine, rifampicin, fluoroquinolones, and macrolides. It details the treatment for different types of leprosy and lepra reactions, emphasizing multidrug therapy (MDT) and alternative regimens. The document also discusses the management of adverse effects and the implications of drug resistance.

1. Dr Naser Ashraf Tadvi

2. Objectives
• Classify anti-leprosy drugs
• Discuss the Mechanism of action, relevant
pharmacokinetics, adverse effects and
contraindications of antileprosy drugs
• Describe the treatment of Paucibacillary and
multibacillary leprosy
• Describe the treatment of type 1 and 2 lepra
reaction

3. Leprosy

4. • Dapsone
SULFONES
• Clofazimine
PHENAZINE DERIVATIVES
• Rifampicin
ANTITUBERCULAR DRUGS
• FLUOROQUINOLONES : Ofloxacin, Moxifloxacin
• MACROLIDES : Clarithromycin
• TETRACYCLINES : Minocycline
OTHER ANTIBIOTICS :

5. • Chemically related to sulfonamides & shares a
common mechanism of action
• Leprostatic at very low concentration
• Not used for other pyogenic infections
• Not used alone always used with rifampicin and/or
clofazimine in MDT for leprosy
Dapsone's chemical name is 4,4'-diamino diphenyl sulfone

6. • Slowly and completely absorbed from GIT
• 70% plasma protein bound
• Produces ten times more concentration
in diseased skin than in normal skin
• t ½ - 24 hrs
• 70-80% excreted in urine
• Drug is excreted in milk
PharmacokineticsDAPSONE

7. • Act as competitive inhibitor of the enzyme DIHYDROPTEROATE SYNTHETASE
(DHPS).
Mechanism of ActionDAPSONE

8. Mechanism of Action
• Folate is necessary for the cell to synthesize nucleic acids and
in its absence cells will be unable to divide.
• Hence the sulfonamide antibacterial exhibit a bacteriostatic
effect
• Folate is not synthesized in mammalian cells, but is instead a
dietary requirement. This explains the selective toxicity to
bacterial cells of these drugs.
DAPSONE

9. Resistance
❑ Secondary resistance usually is seen in lepromatous (multibacillary)
patients treated with a single drug.
RESISTANCE
PRIMARY
Untreated
Patients
SECONDARY
Patients on
treatment
❑ mutation in folP1 of M. leprae
DAPSONE

10. • Mild hemolytic anemia in G6PD deficiency
• Methemoglobinemia
Adverse effectDAPSONE
Dapsone to be avoided if Hb is < 7 gm/dl

11. • Gastric intolerance: nausea , vomiting
anorexia.
• Cutaneous reactions:
• Hepatitis & agranulocytosis
• CNS : headache parasthesia, tinnitus
• Fever
• Sulfone (Dapsone) syndrome
Adverse EffectsDAPSONE

12. • Severe anemia
• G6PD deficiency
• Hypersensitivity reactions
ContraindicationsDAPSONE

13. • Leprosy
• With pyrimethamine
– Resistant Falciparum malaria
– P Jirovecii Infection
– Toxoplasmosis
IndicationsDAPSONE

14. • Phenazine dye
• Leprostatic
• Anti-inflammatory action:
– Major advantage used in ENL
• BIOLOGICAL LAG 6-7 weeks
• Clinical improvement visible by 6th month
CLOFAZIMINE

15. Mechanism of ActionCLOFAZIMINE
• Preferentialy binds to mycobacterial DNA
• Interferes with template function of the DNA
• Alteration of membrane structure and
transport function

16. PharmacokineticsCLOFAZIMINE
▪ Absorption : 40-70%
▪ Lipophilic taken up by macrophages
▪ t 1/2 – 70 days

17. Adverse EffectsCLOFAZIMINE
• Reddish black discoloration of nonexposed
skin
• Discoloration of hair and body secretions
• Dryness of skin, itching & scaling
• Abdominal pain
SMALL BOWEL
SYNDROME
Persistent diarrhea
Abdominal pain Weight loss

18. 1. Pregnancy
2. Liver and kidney disease
3. GI symptoms
ContraindicationsCLOFAZIMINE

19. • Most potent cidal drug for M Leprae
• Rifampicin kills 99.99 % of organisms in 3-7 days
• Free from cross resistance from other organisms.
• The drug has a particular effect in relieving nasal
symptoms and healing of foot ulcers
• Dose – 600 mg once a month

20. FLUOROQUINOLONES
• Ofloxacin, Pefloxacin, Sparfloxacin, Moxifloxacin
• BACTERICIDAL & highly effective
• 22 doses of Ofloxacin ( 400mg/day) - killed 99.99%
• Used as an alternate drug

21. • Only macrolide having significant activity against M.
Leprae
• Clarithromycin is less BACTERICIDAL than Rifampicin.
• 500mg /day in Lepromatous Leprosy patients killed
99.9% bacteria in 8 WEEKS
• Included in alternative regimens
CLARITHROMYCINCLARITHROMYCIN

22. • Semisynthetic derivative of tetracycline
• High lipophilicity
• Bactericidal
MINOCYCLINE
BACTERICIDAL ACTION
Rifampicin > Minocycline > Clarithromycin

23. Classification of Leprosy
Tuberculoid leprosy
• Anaesthetic patch
• CMI is normal
• Lepromin test positive
• Bacilli rarely found in
biopsies
• Prolonged remissions with
periodic exacerbation
Lepromatous leprosy
• Diffuse skin & mucus
membrane infiltration &
nodules
• Deficient
• Negative
• Skin & mucus membrane
lesions bacilli +
• Progresses to anesthesia of
distal parts, atrophy,
ulceration, absorption of
digits

24. Classification of Leprosy
Paucibacillary leprosy
• 1-5 skin lesions
• No nerve or only 1 nerve
involvement
• Skin smear is negative at all
sites
• TT & BT
Multibacillary leprosy
• 6 or more skin lesions
• > 1 nerve involvement
• Negative
• Skin smear positive at any
one site
• LL, BL, BB

25. Multidrug therapy for leprosy
Multibacillary Paucibacillary
Rifampicin 600 mg once
monthly supervised
600 mg once
monthly supervised
Dapsone 100 mg daily
supervised
100 mg daily
supervised
Clofazimine 300 mg/ month
supervised + 50 mg
daily supervised
-
Duration 12 months 6 months

26. Alternative regimens for leprosy
• Intermittent ROM
• Intermittent RMMx
• Ofloxacin or minocycline can be used in place
of clofazimine (if pt refuses Clofazimine)
• 4 drug therapy
– Rifampicin 600 mg + sparfloxacin 200 mg +
clarithromycin 500 mg + Minocycline 100 mg daily
for 12 weeks

27. Treatment : Corticosteroids
Cutaneous ulcerations,multiple
nerve involvement
Type IV Hypersensitivity
(Delayed hypersensitivity response)
TYPE 1 /
REVERSAL REACTIONS
Treatment :
Clofazamine,corticosteroids,
Thalidomide
Existing lesions enlarge ,
become red, inflamed and
painful
Type III Hypersensitivity
(Humoral antibody response)
TYPE2 / ERYTHEMA
NODOSUM LEPROSUM
LEPRA REACTIONS
Lepra ReactionsDAPSONE

28. REACTION PREDNISOLONE CLOFAZAMINE THALIDOMIDE
Reversal
reaction
(Type 1)
up to 1 mg/kg/d
then gradually
reduced
Erythema
Nodosum
Leprosum
(Type 2)
up to 1 mg/kg/d
then gradually
reduced
up to 300 mg up to 400 mg
• Maximum daily dose is shown when single use
• Combination therapy is recommended in ENL
Treatment of Lepra ReactionsDAPSONE

29. Drugs used for the Management of Reactions
• Thalidomide
• Corticosteroids
• Chloroquine
• Clofazamine
• NSAIDS

30. Summary
• Drugs for leprosy
• MDT for leprosy
• Type 1 lepra reaction
• Type 2 lepra reaction