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Anti Leprotic Drugs

This slides are prepared for undergraduate medical (MBBS) class for teaching pharmacology. Materials for slides are taken from Essentials of Pharmacology, KD Tripathi 7th ed, Medical Pharmacology, SK Shrivastav and Sharma & Sharma. Pictures are obtained from google.

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Anti Leprotic Drugs

  1. 1. ANTILEPROTIC DRUGS Dr. MayurA. Chaudhari Assistant Professor Department of Pharmacology Government Medical College, Surat
  2. 2. Objectives Introduction Dapsone Clofazimine Rifampicin Treatment strategies 2
  3. 3. History Image Source: Google images 3
  4. 4. Introduction Chronic granulomatous infection caused by mycobacterium leprae Skin, mucus membrane and peripheral nervous system Prevalent in lower socio economic strata 4
  5. 5. Classification: Drugs Sulfone: Dapsone Phenazine Derivative: Clofazimine Antitubercular : Rifampicin, Ethionamide Other antibiotics: Minocycline, Ofloxacin, Clarithromycin 5
  6. 6. Dapsone Oldest, Cheapest and Most Effective Diamino diphenyl Sulfone (DDS) Inhibit conversion of PABA to folic acid – Leprostatic Spectrum same as sulfonamides but Effective against M.leprae at lower doses Resistance may develop if used as monotherapy 6
  7. 7. Dapsone: Pharmacokinetics Complete and Rapid absorption Peak Conc. In 5 hours and t1/2 24 hours Wide Distribution, Concentrated in Skin, Muscle, Liver and Kidney Metabolized by Acetylation 7
  8. 8. Adverse Effects  GIT Side effects – Anorexia, Nausea,Vomiting  Hemolytic Anaemia  Methaemoglobinaemia Sulfone Syndrome – Fever, Malaise, Exfoliative dermatitis, Jaundice, Anaemia, Methaemoglobinaemia, Lymphadenopathy Lepra Reaction CNS – headache, Nervousness, Insomnia, Paresthesia, Blurring ofVision, Peripheral Neuropathy 8
  9. 9. Therapeutic Uses Leprosy P. Falciparum Malaria Pneumocystis Jiroveci Pneumonia Toxoplasmosis Dermatological Disorders – Acne, Dermatitis herpatiformis, Bullous SLE, Pemphigus 9
  10. 10. Rifampicin Antitubercular, Potent Cidal drug for M.leprae Rapidly renders leprosy patient non contagious 99.99% bacilli killed with in 3-7 days, Lesions start regressing in 2 months Used in Multidrug therapy Shortens duration of treatment 600mg monthly dose given 10
  11. 11. Clofazimine Dye with Leprostatic and anti-inflammatory property Acts by interference with template function of DNA Alteration of membrane structure and transport function Disrupts mitochondrial electron transport chain M.leprae resistant to Dapsone respond to Clofazimine 11
  12. 12. Clofazimine Orally active Accumulates in macrophages and deposited in many tissues T1/2 – 70 hours Used in MDT of leprosy Leprae Reaction MAC infection 12
  13. 13. Adverse Effects • Reddish Black Discoloration of skin, Hair and body secretions • Dryness of skin and itching, Acneform eruptions, Photo toxicity • Conjunctival pigmentation • Nausea, anorexia, abdominal pain, weight loss. • Avoid in pregnancy and renal and liver disease 13
  14. 14. Ofloxacin FQ are highly active against M.leprae Hasten Bacteriological and clinical response Used in alternate regimens instead of rifampicin Reduces duration of treatment Reduces chances of development of resistance 14
  15. 15. Minocycline High lipophilicity helps to penetrate M.leprae Efficacy in-between clarithromycin and rifampicin Rapid relief from lepromatous symptoms Vertigo on long term use Used in alternate regimes 15
  16. 16. Clarithromycin Only macrolide effective in Leprosy Rapid clinical improvement Synergistic action with minocycline Used in alternate regimes 16
  17. 17. Classification: Leprosy Ridley Jopling Tuberculoid (TT) BorderlineTuberculoid (BT) Borderline (BB) Borderline Lepromatous (BL) Lepromatous (LL) Who Multibacillary (MB) Paucibacillary (PB) Single Lesion Paucibacillary 17
  18. 18. 18
  19. 19. NLEP Classification Paucibacillary 1-5 skin lesions No/one nerve involvement Skin smear negative TT and BT Multibacillary 6 or more lesions >1 nerve involvement Skin smear positive LL, BL and BB 19
  20. 20. MultidrugTherapy of Leprosy (MDT) Effective in cases with primary Dapsone resistance Prevent emergence of resistance Quick symptomatic relief, Make patient noncontagious Reduces total duration of therapy Highly effective with reduced relapse and good patient compliance 20
  21. 21. Multibacillary Leprosy Rifampicin – 600mg once a month Supervised Dapsone – 100 mg daily self administered Clofazimine – 300 mg once a month supervised 50 mg daily self administered Duration – 12 months 21
  22. 22. Paucibacillary Leprosy Rifampicin – 600mg once a month supervised Dapsone – 100 mg daily self administered Duration – 6 months 22
  23. 23. Alternative regimen Intermittent ROM : Rifampicin 600 mg + Ofloxacin 400 mg+ Minocycline 100 mg once a month. PBL – 3-6 months, MBL- 12- 24 months. Clofazimine 50mg+ 2 of O/M/Clar for 6 months f/b Clo+ O.M for 18 months If Clofazimine is not tolerated than substitute with O or M in standard MDT Intermittent RMMx – Moxi 400mg+ Mino 200 mg+ Rifampicin 600 mg once a month. PBL – 6 months . MBL – 12 months 23
  24. 24. Reactions in Leprosy Reversal reaction Seen inTT and BL due to delayed hypersensitivity to antigen of M.leprae Cutaneous ulceration, Multiple nerve involvement with Swollen, painful and tender nerves. Prednisolone – 4-60mg daily till reaction subside and tapered gradually Clofazimine is effective 24
  25. 25. Lepra reaction type 2 ( Erythema nodosum leprosum) Occur in LL Arthus type of reaction (JH reaction) Mild , severe or life threatening Existing lesions enlarges, become red, swollen and painful. Malaise, fever and other constitutional symptoms Appearance of newer lesions 25
  26. 26. Lepra reaction Temporary discontinuation of Dapsone in severe cases Clofazimine 200 mg Prednisolone 40-60 mg/day Thalidomide – 100-300 mg OD alternate to prednisolone Chloroquine Analgesics, antipyretics and antibiotics 26
  27. 27. Summary Leprosy Dapsone Rifampicin Clofazimine Alternative drugs Treatment strategies Lepra reaction 27
  28. 28. THAT’S ALL
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This slides are prepared for undergraduate medical (MBBS) class for teaching pharmacology. Materials for slides are taken from Essentials of Pharmacology, KD Tripathi 7th ed, Medical Pharmacology, SK Shrivastav and Sharma & Sharma. Pictures are obtained from google.

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