Apresentacao de hanseníase

1. ANTILEPROTICANTILEPROTIC
DRUGSDRUGS
Dr S.P. Dhanya
Assistant Professor
Pharmacology

5. Types
Paucibacillary Leprosy - Indeterminate
TT
BT
Multibacillary Leprosy – BB
BL
LL

6. Paucibacillary Leprosy
• <5 Hypoanesthetic skin
lesions
• Normal/partially deficient
CMI
• Bacilli rarely found
• Lepromin test +ve
• Prolonged remissions with
periodic exacerbations

7. Multibacillary Leprosy
• >5 Hypoanesthetic
skin lesions
• mucus membrane
involvement
• CMI deficient
• Bacilli numerous
• Lepromin test -ve

8. ANTILEPROTIC DRUGS
•Sulfones-Dapsone( DDS)
•Phenazine derivative
-Clofazimine
•ATT drugs - Rifampicin,
Ethionamide

9. Newer drugs
• Fluroquinolones-
Pefloxacin,Ofloxacin,Sparfloxacin
• Minocycline
• Roxithromycin,Clarithromycin,
Telithromycin
• Rifapentine
• Bromidoprim
• Deoxyfructose serotonin

10. DAPSONEDAPSONE
• Oldest and cheapest
• Related to Sulfonamide
• 4-4diamino diphenyl sulfone
MOA
 Inhibits incorporation of PABA
 Bacteriostatic
 Dose-100mg/day

11. KINETICSKINETICS
 Complete oral absorption
 Undergoes enterohepatic circulation
 Wide distribution in body
 Poor CNS penetration
 Concentrated in skin,muscle,kidney,liver
 Metabolised by acetylation--
ACEDAPSONE

12. Adverse drug reaction
• Mild hemolytic anemia-dose
related
• G-6PD deficient patients—Severe
hemolytic anemia
• Gastric- intolerance, nausea,
gastritis
• CNS-wooly headedness-Headache,
mental symptoms-psychosis

13. • Peripheral neuropathy
• Methhemoglobinemia,agranulocytosis
-rare
• Hepatotoxicity
• Nephrotoxicity
• Cutaneous-
rash,photosensitivity,SJS,TEN

14. Dapsone syndrome
• Maculopapular skin rash
• Exfoliative dermatitis
• Generalised lymphadenopathy
• Fever
• Jaundice
• Occurs within 6 weeks of starting therapy
• Stop dapsone

15. Uses
1. Leprosy
2. Dermatitis herpetiformis
3. Pneumocystitis carni pneumonia
4. Rhinosporidiosis
5. Pustular psoariasis
6. Nodulocystic acne
7. Brown recluse spider bite

16. Rifampicin
• Source-Str. mediterranei
• Spectrum-bactericidal
• MOA-Inhibit DNA dependent RNA
polymerase
• Rapidly renders non infectious
• MIC-0.3µg/ml
• Component of multi drug treatment
• DOSE -600mg/month

17. Uses
1. TB
2. Leprosy
3. MAIC infection
4. Meningococcal and
H. influenza meningitis
5. MRSA
6. Diphtheria, Legionella
7. Brucellosis
8. Leishmaniasis

18. CLOFAZIMINE
• Phenazine dye
• Antileprotic,
• Antiinflammatory--high dose
• Bacteriostatic
• MOA
Binds preferentially to mycobacterial DNA
interferes with template function
• DOSE-100mg/day orally

19. Repository drug-
–Accumulated in fat and
reticuloenothelial system
– Poor CSF penetration
– T1/2=70 days

20. ADR
• Reversible discolouration (Reddish brown) of
skin ,hair ,conjunctiva ,cornea, secretions
• Dreaded-Enteritis
 Abd pain with loose stools
 Deposition of clofazimine crystals in
intestinal mucosa
• Icthyosis, Acne like lesions
• Photo toxicity
Contraindicated in Pregnancy
Hepatic ,renal impairment

21. Other drugs
 OFLOXACIN
Rifampicin resistance
Dose 400mg/day
 PEFLOXACIN
400mg/day
 SPARFLOXACIN
400mg/day

22. • MINOCYCLINE
100mg/day
 CLARITHROMYCIN
500 mg/day

23. Treatment of Leprosy

24. Treatment of PBL
 Dapsone -- 100mg/day self
Rifampicin – 600mg/month-
supervised
Duration --- 6 months

26. Treatment of MBL
Dapsone - 100mg daily - self administered
Rifampicin – 600mg once a month-supervised
Clofazimine- 50mg daily self
300mg once a month-supervised
Duration of treatment - 12 months

27. Alternative regimens of MBL
Clofazimine 50mg/day+
Ofloxacin 400mg/day+
Minocycline 100mg/day
OR
Dapsone 100mg/day+
Ofloxacin 400mg/day+
Rifampicin 600mg/month

28. PBL with single lesion
• Earlier used
• ROM regimen
R RIFAMPICIN 600mg+
O OFLOXACIN 400mg+
M MINOCYCLINE 100mg

29. LEPRA REACTIONS
• Immunologically mediated
• Episodes of acute /subacute
inflammation
• Occurs during the course of leprosy
• Precipitated by malaise,
anxiety,acute infection

30. Type I Type II
• Erythema Nodosum
Leprosum-Relapse
• In lepromatous
• Type III HSR
• Slow and insiduous
• New crops of nodules
Glomerulonephritis,
Hepatitis,Conjunctivitis
Keratitis,fever
• No tenderness
• Reversal/Upgrading or
Downgrading
• In tuberculoid
• Type IV HSR
• Abrupt and sudden
• Existing lesion-
Edema,erythema
• Tenderness

31. • Ulceration+
• Multiple nerve
• Precipitated by drug
• Main treatment-
steroids
• Ulceration-
• Single nerve
• Due to high bacterial
load
• Main
Steroids
Type I Type II

32. Type 1
Mild analgesics
Moderate to severe-Steroids
60 mg/day-Prednisolone
Taper off in 6-12 months
Clofazimine
Azathioprine
Cyclosporine

33. Type II
• Steroids-1 mg/kg/day-taper off in 12 weeks
• Clofazimine-300mg/day
• Thalidomide-300-400mg/day
• Colchicine
• Pentoxyfylline
• Zinc
• Antimony compound
• Chloroquine

34. Thalidomide
• Immunomodulatory
• MOA----Inhibit TNF α,Modulate
IL,lysosomal membrane
stabilisation
• Controls-Neuritis,
Relieve pain
Improve renal function

35. USES
1. ENL
2. Aphthous stomatitis in HIV patient
3. Behcet’s disease
4. TB,Sarcoidosis
5. GVHD
6. IBD
7. Sjogren’s syndrome,DLE/SLE
8. Multiple myeloma

36. Adverse effects
• Teratogenicity-Phocomelia

37. ADR
• Painful peripheral neuropathy
• Eosinophilia
• Drowsiness
• Allergic drug reactions
• Dose-100 mg---3 to 4 times daily