10. antileprotic

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  • It does not growth in culture media so sensitivity test not possible It present in macrophages and remain dormant but alive
  • Clow hand – hyperextension of proximal phalanges, clow toes – dorsal flexion of 1st phalanx and planttar extension of 2nd & 3rd
  • Lepromein test used to determine tissue resistance to leprosy
  • Haemolyticanaemia, methaemoglobinemia- in person having G6PD defiency
  • Haemolyticanaemia, methaemoglobinemia- in person having G6PD defiency
  • Dermatitis - chronic blistering skin- (bubbles on skin filled with watery fluid caused by heat -
  • 10. antileprotic

    1. 1. CHEMOTHERAPY OF LEPROSY
    2. 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. 3. Clinical Manifestation Cardinal features… – – – – Hypo pigmented patches (T) Loss of coetaneous sensation in affected areas. Thickened nerves M. Leprae in skin or nasal passage. Signs of advanced disease… – – – – – – Nodules / lumps in skin of face & ears. Planter ulcers Loss of fingers / toes Nasal depression Foot drop Claw hand and toes.
    4. 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. 5. Classification of Leprosy – Indeterminate Type/Borderline Type – Which ultimately progresses to either tuberculoid or lepromatous
    6. 6. ANTILEPROTIC DRUGS – SULFONE : DAPSONE, SULFOXONE, ACEDAPSONE – PHENAZINE : CLOFAZIMINE – ANTITUBERCULAR : RIFAMPIN – ANTIBIOTICS : FQ: OFLOXACIN Tetra: MINOCYCLIN Macrolids: CLARITHROMYCIN
    7. 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 – – – – More in lepromatous leprosy patients if used monotherapy Primary- harbouring from resistant bacilli Secondary- during treatment Combined with Rifampicin
    8. 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. 9. ADVERSE EFFECTS OF DAPSONE – HAEMOLYTIC ANAEMIA – METHAEMOGLOBINEMIA – GASTRIC INTOLERANCE –decrease later – CUTANEOUS REACTIONS – – – – ALLERGIC RASHES FIXED DRUG ERUPTION HYPERMELANOSIS PHOTOTOXICITY – LEPRA REACTIONS – SULFONE SYNDROME
    10. 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. 11. SULFONE SYNDROME • If lepra reactions develops after 1-2months c/s sulfone syndrome • Characterized by – – – – – Fever Lymphnode enlargement general malaise Jaundice anaemia
    12. 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. 13. CLOFAZIMINE • MOA : – BINDS TO DNA   INTERFERES TEMPLATE FUNCTION of DNA  INHIBITS GROWTH – LEPROSTATIC – ANTI-INFLAMMATORY
    14. 14. KINETICS OF CLOFAZIMINE – P. O. INCOMPLETE ABSORPTION – WIDELY DISTRIBUTED IN TISSUES : PHAGOCYTES – HALF LIFE : 60 – 70 hrs. – Elimination through FAECES
    15. 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. 16. INDICATIONS OF CLOFAZIMINE – DAPSONE RESISTANT LEPROSY – PREFERED IN MDT OF LEPROSY – LEPRA REACTION – ULCERATIVE LESIONS : M. ulcerans
    17. 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. 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. 19. CLARITHROMYCIN – MACROLIDE ANTIBIOTIC – BACTERICIDAL < RIFAMPIN – KILLS 99.9 % BACILLI IN 8 wks – DOSE : 500 mg/day – ALTERNATIVE DRUG
    20. 20. MINOCYCLINE – TETRACYCLIN – RIFAMPIN > MINOCYCLINE > CLARITHROMYCIN – ALTERNATIVE TO CLOFAZIMINE – DOSE : 100 mg/day
    21. 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

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