The document discusses leprosy, a contagious disease caused by Mycobacterium leprae that is now curable due to effective antileprotic drugs like dapsone and clofazimine. It highlights the mechanisms, uses, side effects, and resistance issues associated with these medications, emphasizing the importance of multidrug therapy. Additionally, it provides information on rifampin, an antitubercular drug, noting its absorption, metabolism, and common side effects.

1. PREPARED BY: JEGAN.S. NADAR
ANTILEPROTIC DRUGS

2. LEPROSY
● A contagious disease that affects the skin, mucous membranes, and nerves,
causing discoloration and lumps on the skin and, in severe cases, disfigurement
and deformities
● Leprosy is caused by Mycobacterium leprae
● It 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/defects already incurred may not reverse.
Jegan Nadar

4. CLASSIFICATION

5. Sulfone

6. Dapsone (DDS)
● It is diamino diphenyl sulfone (DDS), the simplest, oldest, cheapest, most active
and most commonly used member of its class
● It is bacteriostatic for M. leprae

7. Dapsone
● Dapsone is structurally related to the sulfonamides and similarly inhibits
dihydropteroate synthetase in the folate synthesis pathway.
● Dapsone-resistance among M. leprae has been reported which necessitated the use of
multidrug therapy
● When dapsone resistance is encountered in an untreated patient, it is called ‘primary’,
and indicates that the infection was contacted from a patient harbouring resistant bacilli
● Resistance which develops during monotherapy in an individual patient with dapsone is
called ‘secondary’
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8. Jegan Nadar

9. Dapsone
● Dapsone is completely absorbed after oral administration and is widely
distributed in the body
● It is 70% plasma protein bound, but more importantly it is concentrated in skin
(especially lepromatous skin), muscle, liver and kidney.
● Dapsone is acetylated as well as glucuronide and sulfate conjugated in liver.
● Metabolites are excreted in urine.
● The plasma t½ of dapsone is variable, though often > 24 hrs
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10. Dapsone
● Dapsone is generally well tolerated at doses 100 mg/day or less.
● Mild haemolytic anaemia is common, Patients with G-6-PD deficiency are more
susceptible
● Gastric intolerance—nausea and anorexia are frequent in the beginning but decreases
later.
● Other side effects are methaemoglobinaemia, headache, paresthesias, mental
symptoms and drug fever.
● Cutaneous reactions include allergic rashes, fixed drug eruption, hypermelanosis,
phototoxicity and rarely exfoliative dermatitis Jegan Nadar

11. ● Sulfone syndrome: It is the reaction which develops 4–6 weeks after starting
dapsone treatment
● Symptoms consists of fever, malaise, lymph node enlargement, desquamation of
skin, jaundice and anaemia.
● It is generally seen in malnourished patients, and has become more frequent
after the introduction of MDT.
● Dapsone should not be used in patients with severe anaemia (Hb < 7 g/dl), G-6-
PD deficiency and in those showing hypersensitivity reactions.
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12. Phenazine derivative

13. Clofazimine
● It is a dye with leprostatic and antiinflammatory properties.
● The putative mechanisms of antileprotic action of clofazimine are:
 Interference with template function of DNA in M.leprae
 Alteration of membrane stucture and its transport function.
 Disruption of mitochondrial electron transport chain.
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14. Clofazimine
● When used alone, the clinical response to clofazimine is slower than that to
dapsone, and resistance develops in 1–3 years.
● Dapsone resistant M. leprae respond to clofazimine, but apparently after a lag
period of about 2 months.
Jegan Nadar

15. Clofazimine
● Clofazimine is orally active (40–70% absorbed).
● It accumulates in macrophages and gets deposited in many tissues including
subcutaneous fat, as needle-shaped crystals.
● However, entry in CSF is poor.
● The t½ is 70 days so that intermittent therapy is possible.

16. Clofazimine
● In the doses employed for MDT, clofazimine is well tolerated
● Skin : The major disadvantage is reddish-black discolouration of skin, especially
on exposed parts. Dryness of skin and itching is often troublesome
● GI symptoms: Nausea, anorexia, abdominal pain, weight loss and enteritis with
intermittent loose stools can occur, particularly when higher doses are used to
control lepra reaction
Jegan Nadar

17. Antitubercular drugs

18. Rifampin (Rifampicin, R)
● It is a semisynthetic derivative of rifamycin B obtained from Streptomyces
mediterranei.
● Rifampin is bactericidal
● M. leprae is highly sensitive to Rifampin
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20. Rifampin
● It is well absorbed orally, (bioavailability is ~ 70%), but food decreases
absorption; rifampin is to be taken in empty stomach.
● It is widely distributed in the body: penetrates intracellularly, enters tubercular
cavities, caseous masses and placenta.
● Though it crosses meninges, it is largely pumped out from CNS by P-
glycoprotein.
● It is metabolized in liver to an active deacetylated metabolite
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21. Rifampin
● Rifampin is a microsomal enzyme inducer—increases several CYP450
isoenzymes, including CYP3A4, CYP2D6, CYP1A2 and CYP2C subfamily.
● It thus enhances its own metabolism as well as that of many drugs including
warfarin, oral contraceptives, corticosteroids, sulfonylureas, steroids, HIV
protease inhibitors, NNRTIs, theophylline, metoprolol, fluconazole,
ketoconazole, clarithromycin, phenytoin, etc.
● Contraceptive failures have occurred
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22. Rifampin
● Hepatitis, a major adverse effect, generally occurs in patients with preexisting
liver disease and is dose-related
● Minor reactions, usually not requiring drug withdrawal and more common with
intermittent regimens, are:
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23. Rifampin
● Cutaneous syndrome: flushing, pruritus + rash (especially on face and scalp),
redness and watering of eyes.
● Flu syndrome: with chills, fever, headache,malaise and bone pain.
● Abdominal syndrome: nausea, vomiting, abdominal cramps with or without
diarrhoea.
● Urine and secretions may become orange-red—but this is harmless.
Jegan Nadar

24. Thank You