MBBS/BDS/ALLIIED SCIENCES AS PER MCI/DCI Curriculum

1. ANTILEPROTIC
DRUGS
Dr. Divya Krishnan MBBS, MD
Associate Professor, Pharmacology
KMCT Medical College

2. LEARNING OBJECTIVES
• Classification
• Dapsone – MOA, PK, ADR
• Clofazimine – MOA, PK, ADR
• Treatment regimens
• Lepra reactions – types & drugs for it

3. Leprosy or HANSEN’S
DISEASE
Named after the scientist
who discovered the
causative organism of
leprosy.
Gerhard Armauer Hansen

4. LEPROSY AS WE KNEW IT
Considered a social
stigma for long

5. LEPROSY AS WE KNOW IT TODAY
National leprosy eradication program (NLEP) launched in
1982. India achieved elimination of leprosy (prevalence rate
<1 per 10,000 population)
TIMELY DIAGNOSIS AND RIGHT TREATMENT CAN CURE
LEPROSY !!

6. INTRODUCTION
❖Chronic granulomatous disease affecting skin,
mucus membranes & nerves.
❖Causative organism : Mycobacterium leprae

7. LEPROSY TYPES
(Clinical classification)
RIDLEY JOPLING CLASSIFICATION
Lepromatous (LL)
Borderline lepromatous (BL)
Borderline (BB)
Borderline tuberculoid (BT)
Tuberculoid (TT)

8. CMI-Cell mediated immunity

9. Lepromatous leprosy

10. LEPROSY TYPES
(Therapeutic classification)
Paucibacillary (PBL)
- Patient has few bacilli
- Non –infectious
- Includes TT,BT types
Multibacillary (MBL)
- Patient has large bacillary load
- Infectious
- Includes LL, BL, BB

11. ANTILEPROSY DRUGS
Classification
• Sulfones - Dapsone
• Phenazine derivative - Clofazimine
• Anti-tubercular drugs - Rifampin, Ethionamide
• Other antibiotics - Ofloxacin, Minocycline,
Clarithromycin

12. DAPSONE (DDS)
Diamino diphenyl sulfone (DDS)
Simplest
Oldest
Cheapest,
Most active
Most common

13. MOA-Inhibits incorporation of PABA into Folic acid.
DAPSONE

14. Pharmacodynamics
• Leprostatic
• Inhibits other bacteria (at higher conc)/BUT NOT
USED DUE TO TOXICITY OF HIGH DOSE
• Resistance-Primary /secondary

15. Pharmacokinetics
• Good oral absorption
• Concentrated In skin, muscle, liver, kidney
• Metabolised in liver by conjugation (acetate
/glucuronide/sulfate conjugations)
• Excretion through bile, reabsorbed from intestine and
finally excreted in urine
• T1/2 = >24hr
• Cumulative drug : retension in tissues

16. ADR (Well tolerated at 100m/day or less)
• GI symptoms -Nausea, anorexia, vomiting (at the start of
therapy only)
• Haemolytic anemia -Dose related,G6PD deficiency
• Allergic reactions -Rashes, phototoxicity, Exfoliative
dermatitis, fixed drug eruption
• Others - Methaemoglobinemia, hepatitis, agranulocytosis
• Sulfone syndrome : Reaction occurs 4-6 wks after start of
dapsone treatment/ fever, malaise, lymph node
enlargement, desquamation of skin, jaundice, anemia.
Stop Dapsone temporarily. Treat with steroids & supportive
measures.

17. Contraindications
• Severe anemia (Hb<7g)
• G6PD deficiency
• Hypersensitive patients

18. Uses
• Leprosy
• CLQ resistant malaria (in combination with
pyrimethamine)
• Toxoplasmosis
• Dermatitis herpetiformis
• Pneumocystis jirovecii pneumonia in AIDS patients

19. CLOFAZIMINE
• Dye
• Leprostatic drug
• Has additional anti-inflammatory actions

20. MOA
- Interferes with template function of DNA in
Mycobacterium leprae bacteria.
- Alteration of bacterial membrane structure & transport.
- Disruption of mitochondrial electron transport chain.

21. Pharmacokinetics
• Orally active
• High accumulation in fat
• Poor CSF entry
• T ½ -70 days (intermittent therapy is possible)

22. ADR (well tolerated)
Skin
• Reddish black discoloration of skin, conjunctiva, hair,
body secretions
• Dryness, itching, scaling
• Acneiform eruptions, phototoxicity
G.I
Nausea, anorexia ,abdominal pain, loose stools, weight
loss (irritant effect of drug/deposition of crystals in
intestinal submucosa).
(Take the drug with meals to lessen these effects)

23. Uses
• Component of multidrug therapy for leprosy
• Lepra reactions (Anti-inflammatory actions)
CI
• Pregnancy
• Liver disease
• Kidney disease

24. RIFAMPIN
• Most potent CIDAL drug for M. leprae
• Rapidly renders patient non-contagious- kills 99.9%
bacteria in 1 week
• Rapid clinical improvement
- nasal symptoms (2-3wks)
- skin lesions (2mths)
(NERVE DAMAGE NOT BENEFITTED)

25. Use (as a component of Multidrug therapy for
leprosy)
• Shortens duration of treatment
• Prevents development of resistence
• Once a month dose is effective
(Other uses of rifampicin already covered )
Dose :600mg/month
CI : liver & kidney disease

26. ETHIONAMIDE
• Significant anti- leprotic activity
• Expensive
• Hepatotoxic
• 250 mg/day
• Used only if absolutely necessary

27. OTHER ANTIBIOTICS
✓ Ofloxacin,Pefloxacin,Moxifloxacin (FQs)
✓ Minocycline (Tetracycline)
✓ Clarithromycin (Macrolide)
- Bactericidal action against M. Leprae
- Used in Alternative MDT regimens where Rifampicin
cannot be used (not in standard MDT regimen wherein
Rifampicin used)

28. TREATMENT
OF LEPROSY

29. CONVENTIONAL THERAPY
Monotherapy with Dapsone
Long duration of treatment
Only symptomatic relief.
No bacterial cure in some
Resistance emerged
Not used now

30. MULTIDRUG THERAPY (MDT)
• Effective in primary Dapsone resistance
• Prevents emergence of resistance.
• Quick symptom relief
• Renders MBL cases non-contagious fast
• Prevents progression/complications of disease.
• Decreases total duration of therapy
• Less chances of relapse
• Relapse cases can be re-treated with same MDT

31. MULTI DRUG THERAPY (MDT)
STANDARD REGIMEN
For PBL
• Dapsone 100mg daily,
Self administered.
• Rifampin 600mg once a
month supervised
6 months
For MBL
• Dapsone 100mg daily
self-administered.
• Rifampin 600mg once a
month supervised
• Clofazimine 300mg once a
month supervised+50mg
daily self administered
12 months
Child dose : Rifampin – 10mg/kg Dapsone : 2mg/kg
Chlofazimine : 1mg/kg daily dose +6mgkg once monthly

32. How it is practically done-
A sample for a PBL case.

33. Alternative regimens(for additional reading only)
ROM regimen
Rifampicin 600 + ofloxacin
400mg + Minocycline
100mg
All once a month for 3-
6months
Used for solitary lesion
Other regimens including
FQs/Macrolide/tetracycli
ne antibiotics
Used in case of patients
who cannot be
administered Rifampicin

34. REACTIONS
IN
LEPROSY

35. Reactions in Leprosy
• Type 1 reaction (Reversal reaction)
• Type 2 reaction/Lepra reactions /Erythema Nodosum
Leprosum

36. Type 1 reaction(reversal reaction)
• Type IV Delayed hypersensitivity reaction to M.leprae antigens.
• Seen in TT, BT cases.
• Cutaneous ulceration, multiple nerve involvement with pain &
tenderness occur suddenly even after treatment completion
• Treatment - Glucocorticoids/Clofazimine

37. Type 2 reaction(Erythema nodosum leprosum)
• Type III hypersensitivity reaction
• Seen in LL cases
• Abrupt onset, existing lesions enlarge, become red, swollen,
painful, new lesions; malaise, fever, constitutional
symptoms(mild to severe forms)
• Treatment-Antipyretics/analgesics/antibiotics (symptomatic)
Clofazimine 200mg/day (Antiinfammatory)
Prednisolone 40-60 mg/day till reaction controlled,
then tapered over 8-12 weeks( given for severe
cases)
Temporary discontinuation of Dapsone (severe
cases)
Chloroquine (alternatives)
Thalidomide (alternatives)

38. IMPORTANT QUESTIONS
• Classify drugs for leprosy
• Dapsone – SN
• Clofazimine – SN
• MDT – leprosy
• Drugs for reactions in leprosy

39. THANK YOU