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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