DRUGS FOR LEPROSY.pptx

review on leprosy drugs

1. DRUGS FOR LEPROSY MOORTHI ABINAYA NALI SOMASHEKAR SANTHOSH

2. INTRODUCTION Leprosy is a chronic infectious disease caused by Mycobacterium leprae. Host defenses are crucial in determining the patient's response to the disease, the clinical presentation, and the bacillary load. These factors also influence the length of therapy and the risk of adverse reactions to medication. The drugs used in WHO-MDT are a combination of rifampicin, clofazimine and dapsone for MB leprosy patients and rifampicin and dapsone for PB leprosy patients. Among these rifampicin is the most important antileprosy drug and therefore is included in the treatment of both types of leprosy.

3. Dapsone ACTION Dapsone is Leprostatic Dapsone  is a sulfone drug used to treat acne vulgaris, Hansen's disease, and dermatitis herpetiformis. Dapsone acts against bacteria and protozoa in the same way as sulphonamides , that is by inhibiting the synthesis of dihydrofolic acid through competition with para-amino-benzoate for the active site of dihydropteroate synthetase. The anti-inflammatory action of the drug is unrelated to its antibacterial action and is still not fully understood. Dapsone is completely absorbed on oral administration and reaches high concentrations in skin. it is metabolized in the liver and excreted in bile.

4. ADVERSE EFFECT Dapsone is well-tolerated. Anorexia, nausea and vomiting are common. Fever, Pruritus, Rashes and Dermatitis can also occur. Haemolytic anaemia is the most important dose related toxicity (more common in patients with G-6-PD deficiency).Iron preparations should be given to prevent anaemia. Hepatitis and Agranulocytosis are seen. Patient with Lepromatous leprosy may develop Lepra reactions.

5. Rifampin It is rapidly bactericidal to M. leprae and is highly effective, a single dose of 1500 mg can kill 99% of the lepra bacilli. it can be conveniently given once monthly. Used in combination with dapsone, it shortens the duration of treatment. Given alone resistance develops. Mechanism of Action Rifampin produces bactericidal antimicrobial activity by inhibiting DNA-dependent RNA polymerase (RNAP) either by sterically blocking the path of the elongating RNA at the 5′ end or by decreasing the affinity of the RNAP for short RNA transcripts. It specifically inhibits the microbial RNAP, halting further RNA synthesis.

6. Clofazimine A dye, has weak bactericidal actions against M. leprae. It also has anti inflammatory properties which is useful in suppressing lepra reactions. It is used orally in multidrug regimens. Treatment with clofazimime results in a reddish-black discolouration of the skin specially on the exposed parts which remains for several months. It can also cause dryness of skin, itching and phototoxicity Clofazimine is indicated for the treatment of lepromatous leprosy, including dapsone-resistant lepromatous leprosy and lepromatous leprosy complicated by erythema nodosum leprosum . To prevent the development of drug resistance, it should be used only in combination with other antimycobacterial leprosy treatments.

7. Ethionamide It is bactericidal to lepra bacilli but is more expensive and more toxic than dapsone. It can came gastric irritation, peripheral neuritis and hepatotoxicity. Ethionamide is a prodrug which is activated by the enzyme ethA , a mono-oxygenase in Mycobacterium tuberculosis, and then binds NAD+ to form an adduct which inhibits InhA in the same way as isoniazid. The mechanism of action is thought to be through disruption of mycolic acid. Ethionamide can be used in multidrug regimen in patients who cannot tolerate clofazimine. Protionamide is similar to ethionamide.

8. OTHER DRUGS Ofloxacin is suitable for use in multidrug regimens in leprosy along with rifampin. Minocycline It is tetracycline found to have useful activity against M. leprae and is being tried in combination regimens to shorten the duration of treatment. Clarithromycin It is a macrolide antibiotic that has bactericidal activity against M. leprae' Given 500 mg daily for 28 days can kill 99% of viable bacilli.

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