Anti- Leprosy Drugs

Drugs used in treatment of Leprosy: 

Drugs used in treatment of Leprosy Leprosy is caused by Mycobacterium Leprae Two major types 1-Paucibacillary or Tuberculoid Leprosy 2-Lepromatous Leprosy

Drugs used in treatment of Leprosy: 

Sulfones: Dapsone, Acedapsone Rifampin Clofazimine Drugs used in treatment of Leprosy

DAPSONE: 

DAPSONE Dapsone is a sulfone .Closely related to sulfonamides Chemistry: Diaminodiphenylsulfone Pharmacokinetics : Dose : 100 mg/d orally. Well abs. from gut. Widely distributed t 1/ 2 – 1-2days– retained in skin muscles ,liver & kidney. Heavily infected skin may contain more drug. Metabolized by Acetylation . Secreted in to bile , Excretion mainly in urine , dosage adjustment in renal failure.

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MOA It is bacteriostatic ,inhibits folate synthesis. PABA Dihydrofolic Acid (Folate) Tetrahydrofolic Acid Purines DNA Dihydropteroate Synthetase Dihydrofolate Reductase Dapsone X

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Antibacterial spectrum: M.Leprae Pneumocystis Jiroveci (Carnii) Resistance: Develops rapidly when used alone in lepromatous leprosy

Therapeutic Uses: 

Therapeutic Uses 1.Leprosy: In combination with other drugs For Tuberculoid Leprosy: for 6 months Dapsone & Rifampin For Lepromatous Leprosy: 2 years. Dapsone , Rifampin & Clofazimine. 2.Pneumocystis Jiroveci pneumonia in AIDS: for prevention & treatment. 3.For resistant malaria: Dapsone & Pyrimethamine

Adverse Effects: 

Adverse Effects Hemolysis specially in G6PD deficiency Methaemoglobinaemia GIT intolerance Drug Fever , Pruritis & various skin rashes. Erythema nodosum leprosum ( Sulfone syndrome), in malnourished people It resembles exacerbation of lepromatous leprosy Can be suppressed by corticosteroids / thalidomide

Rifampin: 

Rifampin Important, safe & effective bactericidal Anti Leprosy drug 600 mg daily is effective for Lepromatous Leprosy--- resistance develops, if used alone. Given in combination therapy, with Dapsone &/ or Clofazimine ,600 mg once monthly.

Clofazimine: 

Clofazimine Phenazine dye MOA : Clofazimine is lepraecidal , also some activity against M avium intracellulare . Exact MOA not clear: It binds to DNA. It prevents it from serving as a template for future DNA replication. Its redox properties may lead to the generation of cytoxic oxygen radicals, toxic to My.leprea

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Clinical Uses: Alternative to Dapsone 1.Leprosy In combination therapy Dapsone resistant leprosy Patients are intolerant to Dapsone 2. Also Prevents Erythema nodosum . 3. Some activity against M avium intracellulare . Dose: 100mg /d orally Adverse Effects: Skin discoloration, from red brown to nearly black GIT intolerance

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Miscellaneous anti leprotics: Ethionamide: Substitute for Clofazimine, 250---375mg/d Thalidomide : for Erythema nodosum leprosum, 100-300mg It is Teratogenic New agents in animal trials: Minocycline , Clarithromycin ,Pefloxacin , Ofloxacin

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Atypical Mycobacteria: They are generally resistant to most of the anti-TB drugs Mycobacterium avium complex (MAC) produces disseminated infection in HIV patients For primary prophylaxis ---- Clarithromycin or Azithromycin. For treatment: Clarithromycin or Azithromycin , Amikacin , Ciprofloxacinwith Ethambutol & Rifabutin M-marinum, M. Avium-intracellulare, M. ulcerans infections although asymptomatic may be treated with combinations of Anti TB & other antimicrobials.