Leprosy caused by mycobacterium leprae has been considered

� Leprosy, caused by mycobacterium leprae, has been considered incurable since ages and bears a social stigma. � Due to availability of effective antileprotic drugs now, it is entirely curable, but deformities already incurred may not reverse.

Sulfone � Dapsone 2. Phenazine Derivatives � Clofazimine 3. Antitubercular Drugs � Rifampin � Ethionamide 1.

4. Other Antibiotics � Ofloxacin � Minocycline � Clarithromycin

� It is diamino diphenyl sulfone (DDS), the simplest, oldest, cheapest, most active and most commonly used member of it is class. � All other sulfones are converted in the body to DDS, many have been used, but none is superior. � It is available in 25, 50, 100 mg tabs.

� Inhibition of PABA incorporation into folic acid. � It is antibacterial action is antagonized by PABA. � It is leprostatic at low concentrations, and at relatively higher concentrations arrests the growth of many other bacteria sensitive to sulfonamides.

� Dapsone resistance among M. Leprae, first noted in 1964, has spread and has necessitated the use of multi-drug therapy (MDT).

� Dapsone is completely absorbed after oral administration and is widely distributed in the body. � Dapsone is more concentrated in the skin, muscle, liver and in the kidney. � Metabolites are excreted in bile and reabsorbed from the intestine. � The plasma half life of dapsone is variable. � Elimination takes 1 -2 weeks longer.

� Leprosy � Chloroquine resistant malaria (in combination with Pyrimethamine) � Other bacteria's who are sensitive to sulfonamides.

� Mild haemolytic anemia � Nausea � Anorexia � Headache � Fever � Mental symptoms � Allergic rashes � Photo toxicity � Hepatitis

� Hypersensitivity � Sever � G 6 PD anemia (less than 7 Hb)

� It is a dye with leprostatic and antiinflammatory properties, acts probably by interfering with template function of DNA in M. Leprae. � When used alone, resistance to clofazimine develops in 1 -3 years. � Clofazimine is orally active (40 -70% absorbed).

� The half life of Clofazimine is 70 days, so that intermittent therapy is possible. � Clofazimine is used as component of multidrug therapy of leprosy. � Because of it is anti-inflammatory property, it is valuable in lepra reactions. � Occasionally, it is used as a component of MDT.

� Clofazimine is available in 50, 100 mg capsules for different brand names like clofozine, hansepran.

� Reddish black discoloration of skin. � Discoloration of hair � Dryness and itching of skin � Acne � Photo toxicity � Conjuctival pigmentation

� Loose stool � Nausea � Abdominal pain � Anorexia � Weight loss

� Clofazimine is to be avoided during early pregnancy and in patients with liver or kidney damage.

� It is important antitubercular drug and bactericidal to M. Leprae. � Upto 99. 999% M. Leprae are killed in 3 -7 days, however it is not satisfactory if used alone, some bacilli persist even after prolonged treatment- resistance develops. � It has been included in the multi drug therapy of leprosy.

� The 600 mg monthly dose used in leprosy is relatively non-toxic and does not induce metabolism of other drugs. � It should not be given to patients with hepatic or renal dysfunction.

� Ethionamide is a antitubercular drug that has significant antileprotic activity, but causes Hepatotoxicity in 10% patients. � It has been used as an alternative to Clofazimine but other substitutes are preferred. � It should be used 250 mg per day only when absolutely necessary.

� Ofloxacin � Pefloxacin � Gatifloxacin � Sparfloxacin � Minocycline � Clarithromycin

� Many trials have evaluated ofloxacin as a component of MDT and found it to hasten the bacteriological and clinical response. � Over 99. 9% bacilli were found to be killed by 22 daily doses of ofloxacin monotherapy. � It is used in case of rifampin cannot used or to shorten the duration of treatment. � Dose: 400 mg per day.

� Minocycline has high lipophilicity and active against M. Leprae. A dose 100 mg per day produces peak blood levels that exceed maximum concentration. � It is antibacterial activity is less than the rifampin. � It is included multiple Drug Therapy.

� Leprosy is a chronic granulomatous infection caused by mycobacterium Leprae, primarily affecting skin, mucous membrane and nerves. � It is more prevalent among the lowest socioeconomic strata. � Many patients exploit it for begging and donot come forward for treatment.

� Two polar types- lepromatous (LL), and tuberculoid (TT) with four intermediate forms- borderline (BB), borderline lepromatous (BL), borderline tuberculoid (BT) and indeterminate (I) of the disease are recognized.

� For operational purposes, leprosy has been divided into: 1. Paucibacillary leprosy (PBL): Noninfectious, this includes TT, BT, I. 2. Multibacillary leprosy (MBL): infectious and this includes LL, BB.

1. � � Multibacillary Rifampin 600 mg once a month, supervised. Dapsone 100 mg daily, self administered. Clofazimine 300 mg once a month supervised, and 50 mg daily self administered. The duration is 12 months or it can be 2 years.

2. Paucibacillary � Rifampin 600 mg once a month supervised. � Dapsone 100 mg self administered. � Dapsone 100 mg daily. � the duration is 6 months.

� ID/CC: A 19 year old military recruit comes to his medical officer complaining of red urine and orange colored staining of his T-shirt, he also complains that every time he takes rifampin, he feels as if he has the flu. � HPI: He underwent a routine physical exam and laboratory tests prior to joining the military camp and was started on rifampin at that time for meningococcal carrier state.

� PE: VS: normal, PE: muscular male in no acute distress, no jaundice, hepatomegaly, spider angiomas or parotid enlargement; nonpruitic maculopapular rash on chest and petechial hemorrhages on limbs. � Labs: AST and ALT moderately increased. UA: Proteinuria. CBC: thrombocytopenia. � Imaging: CXR is normal

� Treatment: Switch to Ceftriaxone or ciprofloxacin for eradication of meningococcal carrier state. � Discussion: Rifampin is an antituberculous drug that acts by inhibiting DNA-dependant RNA polymerase. One of its major drawbacks is the rapid development of resistance if used alone. Other side-effects include discoloration of urine and sweat with a yellowish orange, hepatic damage, skin rash, thrombocytopenia, and increased metabolism of anti-coagulants and HIV protease inhibitors.

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