1. LEPROSY Caused by bacterium Patients are classified into infectious or noninfectious on the basis of the type and duration of disease and effects of therapy.

2. Clinical types of leprosy 1-Tuberculoid leprosy 1-Tuberculoid leprosy Skin macules, with clear centers and well defined margins. Skin macules, with clear centers and well defined margins. 2- Mycobacterium leprae appear during activity 2- Mycobacterium leprae appear during activity 3- Noncaseating foci 3- Noncaseating foci 4- Widely disseminated lepromatous form 4- Widely disseminated lepromatous form

3. Patients with tuberculoid leprosy may develop reversal reactions which are manifestations of delayed hypersensitivity to antigen of M.leprae. Therapy with corticosteroids or clofazimine is effective. Patients with tuberculoid leprosy may develop reversal reactions which are manifestations of delayed hypersensitivity to antigen of M.leprae. Therapy with corticosteroids or clofazimine is effective.

4. Sulfones All clinically useful sulfones are derivatives of dapsone e.g. sulfoxone All clinically useful sulfones are derivatives of dapsone e.g. sulfoxone Dapsone remains the agent most usefully clinically Dapsone remains the agent most usefully clinically

5. Dapsone Is bacteriostatic for M.leprae Is bacteriostatic for M.leprae Competitive inhibitor of dihydropteroate synthase and prevent the normal bacterial utilization of PABA. Competitive inhibitor of dihydropteroate synthase and prevent the normal bacterial utilization of PABA. Drug resistance usually emerge in patients treated with a single drug. Drug resistance usually emerge in patients treated with a single drug.

6. Pharmacokinetics Dapsone are absorbed rapidly and completely from GIT, while sulfoxone are absorbed incompletely. Dapsone are absorbed rapidly and completely from GIT, while sulfoxone are absorbed incompletely. Dapsone half-life is 1-2 days Dapsone half-life is 1-2 days The sulfones are distributed throughout total body water and all tissues. The sulfones are distributed throughout total body water and all tissues. Dapsone is retained mainly in skin, muscle, liver & kidney.Traces of the drug are present in these organs up to 3 weeks after the therapy is stopped. Dapsone is retained mainly in skin, muscle, liver & kidney.Traces of the drug are present in these organs up to 3 weeks after the therapy is stopped.

7. Pharmacokinetics All sulfones are excreted into bile ( large amount are excreted in feces), part of the drugs are reabsorbed in the intestine ( prolong half-life). All sulfones are excreted into bile ( large amount are excreted in feces), part of the drugs are reabsorbed in the intestine ( prolong half-life). Excretion into urine is variable, in renal failure, the dose may have to be adjusted. Excretion into urine is variable, in renal failure, the dose may have to be adjusted. Dapsone is acetylated in liver and the rate is genetically determined Dapsone is acetylated in liver and the rate is genetically determined

8. Therapeutic uses Tuberculoid leprosy together with rifampicin. Tuberculoid leprosy together with rifampicin. Lepromatous leprosy in combination with rifampicin and clofazimine Lepromatous leprosy in combination with rifampicin and clofazimine Treatment should continue for 2-3 years and sometimes for life in some patients. Treatment should continue for 2-3 years and sometimes for life in some patients.

9. Adverse effects 1-Hemolysis( mainly in patients with glucose 6- phosphate dehydrogenase deficiency). 1-Hemolysis( mainly in patients with glucose 6- phosphate dehydrogenase deficiency). 2- Methemoglobinemia ( mainly in genetic deficiency in NADH- dependent reductase). 2- Methemoglobinemia ( mainly in genetic deficiency in NADH- dependent reductase). Anorexia,nausea, vomiting Anorexia,nausea, vomiting 3-Headache, nervousness, insomnia, blurred vision, reversal peripheral neuropathy, psychosis. 3-Headache, nervousness, insomnia, blurred vision, reversal peripheral neuropathy, psychosis. 4-Drug fever, skin rash. 4-Drug fever, skin rash.

10. Adverse effects 5- Erythema nodosum leprosum may be suppressed by corticosteroides or by thalidomide. 5- Erythema nodosum leprosum may be suppressed by corticosteroides or by thalidomide. 6- Sulfone syndrome, exacerbation of lepromatous leprosy. 6- Sulfone syndrome, exacerbation of lepromatous leprosy.

11. Rifampin Bactericidal for M.leprae Bactericidal for M.leprae Effective in combination therapy in lepromatous leprosy Effective in combination therapy in lepromatous leprosy

12. Clofazimine Phenazine dye Phenazine dye Bactericidal against M.intracellulare. Bactericidal against M.intracellulare. May acts through inhibiting DNA binding May acts through inhibiting DNA binding It has an antiinflammatory effect and prevents the development of erythema nodosum leprosum. It has an antiinflammatory effect and prevents the development of erythema nodosum leprosum.

13. Clofazimine Is absorbed by the oral route. Is absorbed by the oral route. Stored in reticuloendothelial tissues, skin. Stored in reticuloendothelial tissues, skin. Slowly released,its half-life may be 2 months. Slowly released,its half-life may be 2 months. Excreted in feces. Excreted in feces.

14. Clinical uses 1- Dapsone- resistant bacilli 1- Dapsone- resistant bacilli 2-Patients intolerant to sulfone compounds 2-Patients intolerant to sulfone compounds 3- Lepromatous leprosy 3- Lepromatous leprosy 4- Chronic skin ulcers ( caused by Mycobacterium ulcerans). 4- Chronic skin ulcers ( caused by Mycobacterium ulcerans).

15. Adverse effects 1- Discoloration of skin( redbrown-black) 1- Discoloration of skin( redbrown-black) 2-Gastrointestinal intolerance 2-Gastrointestinal intolerance 3- Eosinophilic enteritis 3- Eosinophilic enteritis

16. Miscellaneous Agents Thalidomide Thalidomide Effective in treatment of erythema nodosum leprosum Effective in treatment of erythema nodosum leprosum Inhibits tumor necrosis factor – α. Inhibits tumor necrosis factor – α. Teratogenic Teratogenic

17. Ethionamide Ethionamide Used as substitute for clofazimine. Used as substitute for clofazimine.