Anti-leprotic drugs

This is for educational purpose.

1. Unit III: Chemotherapy b. Antileprotic agents Presented by: Mirza Anwar Baig M.Pharm (Pharmacology) Anjuman I Islam's Kalsekar Technical Campus, School of Pharmacy. New Panvel,Navi Mumbai

2. What is Leprosy? Leprosy, caused by Mycobacterium leprae , has been considered incurable since ages and bears a social stigma. Now, it is entirely curable , but deformities/defects already incurred may not reverse . CLASSIFICATION: 1. Sulfone Dapsone (DDS) 2. Phenazine derivative Clofazimine 3. Antitubercular drugs Rifampin , Ethionamide 4. Other antibiotics Ofloxacin , Moxifloxacin , Minocycline , Clarithromycin

3. Dapsone (DDS): It is diamino diphenyl sulfone (DDS) Simplest, oldest, cheapest, most active and most commonly used member of its class. Activity and mechanism Dapsone is chemically related to sulfonamides and has the same MoA (inhibition of PABA incorporation into folic acid by folate synthase ). The antibacterial action of dapsone is antagonized by PABA. It is leprostatic . Specificity for M. leprae may be due to difference in the affinity of its folate synthase . Dapsone resistant M. leprae have mutated folate synthase which has lower affinity for dapsone .

4. Compiled by: Prof.Anwar Baig (AIKTC,SOP) 4

5. Pharmacokinetics: Completely orally absorbed, widely distributed in the body, CSF penetration is poor. 70% plasma protein bound , concentrated in skin, muscle, liver and kidney. Acetylated as well as glucuronide and sulfate conjugated in liver. Excretion occurs mostly in urine. Plasma t½ often > 24 hrs . Elimination takes 1–2 weeks or longer .

6. Adverse effects: Mild haemolytic anaemia Gastric intolerance Sulfone syndrome It is the reaction which develops 4–6 weeks after starting dapsone treatment: consists of fever, malaise, lymph node enlargement, desquamation of skin, jaundice and anaemia . Contraindications: Dapsone should not be used in patients with severe anaemia ( Hb < 7 g/dl), G-6-PD deficiency and in those showing hypersensitivity reactions.

7. Clofazimine ( Clo ): It is a dye with leprostatic and antiinflammatory properties. Mechanisms of action are: • Interference with template function of DNA in M.leprae . • Alteration of membrane structure and its transport function. • Disruption of mitochondrial electron transport chain. Clinical response to clofazimine is slower than that to dapsone , and resistance develops in 1–3 years. Orally active (40–70% absorbed). Accumulates in macrophages and gets deposited in many tissues including subcutaneous fat, as needle-shaped crystals. Entry in CSF is poor. t½ is 70 days so that intermittent therapy is possible.

8. Adverse effects: Skin : Reddish-black discolouration of skin Discolouration of hair and body secretions Dryness of skin Phototoxicity . Conjunctival pigmentation may create cosmetic problem. GI symptoms: Nausea, anorexia, abdominal pain , weight loss and enteritis with intermittent loose stools can occur Deposition of clofazimine crystals in the intestinal submucosa . Avoided during early pregnancy and in patients with liver or kidney damage.

9. Other drugs: Rifampin (R) Ofloxacin ( fluoroquinolones ) Minocycline ( tetracycline) Clarithromycin ( macrolide antibiotic)