Professional Documents
Culture Documents
Introduction
• Mycobacterium leprae
• History
– Chaulmoogra Oil
– Antibiotic Era
Classification
1. Sulfone
– Dapsone { 4-4‘Diaminodiphenylsulfone}
2. Phenazine derivative
– Clofazimine
3. Antitubercular drugs
– Rifampin
– ethionamide
4. Other antibiotics
– Ofloxacin
– Minocycline
– Clarithromycin
Dapsone
• The simplest, oldest, cheapest, most active and
most commonly used member of the class
• Mechanism of action:
– Inhibits incorporation of PABA into folic acid
– Leprostatic
– Peak serum conc. after 100mg/day exceeds MIC for
M.leprae by 500 times and continues to be active
against even moderately resistant bacteria
Dapsone
• Pharmacokinetics
– Completely absorbed after oral admn.
– T1/2 is 20 -30 hrs, drug undergoes acetylation,
conjugation in liver, enterohepatic circulation and
finally excreted through urine
– Cumulative T ½ is very long{1-2weeks}
– Distributed throughout total body water and all
tissues, they tend to be retained in skin and
muscle and especially in liver and kidney
Dapsone
• Adverse effects
– Mild hemolytic anemia : oxidizing property, dose
dependent
– Severe hemolytic anemia : Glucose-6-phosphate
dehydrogenase deficiency, Erythrocyte and bone marrow
disorders
– Gastric intolerance : anorexia, nausea, vomiting
– Skin manifestations : allergic rashes, FDE, phototoxicity ,
hypermelanosis
– Others : headache, methemoglobinemia, hepatitis,
agranulocytosis
– Sulfone syndrome : develops 4 to 6 weeks of dapsone
treatment, fever, malaise, LN enlargement, jaundice,
anemia (Rx clofazimine)
Clofazimine
• It is a dye with antileprotic and anti-inflammatory
effects
• Mechanism of action
– (?) by interfering template function of DNA
– inhibit microbial K+ transport
• Pharmacokinetics
– Orally active (40-70% absorption)
– Accumulates in many tissues esp. fat
– Poor penetration into CSF
– T ½ ~70 days
Clofazimine
• Adverse effects
– Skin : reddish-black discoloration of skin esp. in
exposed body parts & lesions, dryness, pruritis, acne
form eruption, conjunctival pigmentation,
discoloration of hairs and body fluids
– GI symptoms :
• Early- anorexia, nausea, loose stools, abdominal pain,
weight loss, …….(Rx )
• Late- Eosinophilic enteritis
– To be avoided in early pregnancy, liver or kidney
diseases
Rifampin
• Bactericidal, kills upto 99.99% bacteria in 3-7 days
• Rapidly renders leprosy patients noncontagious
• Mechanism of action
– Inhibits DNA-dependent RNA polymerase of
mycobacterium
• Pharmacokinetics
– Orally active, enterohepatic circulation ( T 1/2 )
– Up to 30% of a dose of the drug is excreted in the urine
and 60% to 65% in the faeces
– Adjustment of dosage is not necessary in patients with
impaired renal function
Rifampin
• Adverse effects
– Very rare in doses taken for leprosy
– Includes rash, fever, nausea, vomiting
– To be avoided in pre-existing hepatic disorders
– No reduction in dosage required in renal
dysfunction
Other antibiotics
• Ofloxacin
– Bactericidal, and highly active
– Over 99.9% bacteria killed in 22 days
– Included in alternative treatment regimens, and
where rifampicin cannot be used
– Dosage – 400 mg/day
– Other fluoroquinolones that can be used are
sparfloxacin, pefloxacin
Other antibiotics
• Minocycline
– Highly active, bactericidal, 100mg/day achieves 10
to 20 times MIC
– being tried in alternative regimens
• Clarithromycin
– Less active than minocycline
– Monotherapy kills 99.9% bacteria in ~8 weeks
– Used in alternative regimens
– 500mg/ day dose
Classification of disease
• For operational purposes leprosy has been
divided into
– Paucibacillary leprosy (<5 lesions)
– Multibacillary leprosy (≥5 lesions, or demonstration
of even 1 bacteria on Split skin smear)
• Histopathologically, has many classifications eg.
Madrid classification, Ridley- Jopling, Indian
classification etc.
Effectiveness of multidrug therapy
• PB patients treated with MDT are cured within
six months
• MB patients treated with MDT are cured
within 12 months
• Patients are no longer infectious to others
after the first dose of MDT. In other words,
transmission of leprosy is interrupted
• No resistance of the bacillus to MDT has been
detected
WHO Treatment Regimen
Paucibacillary leprosy Multibacillary leprosy