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Drugs Used in Leprosy

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Drugs Used in Leprosy Powered By Docstoc
					• Mycobacterium leprae

• Leprosy is primarily a granulomatous disease of the
  peripheral nerves and mucosa of the upper respiratory
  tract

• Skin lesions are the primary external sign.

• Body parts can become numb
Classification
• 2 types – Lepromatous ( LL)
            Tuberculoid ( TT)
Paucibacillary

• It is characterized by :
 hypopigmented skin macules and anaesthetic patches
  because of damaged peripheral nerves that have been
  affected by the human host's immune cells.

• Leprosy characterized by one to five numb patches, is
  mainly tuberculoid in type and is treated for 6 months
  with dapsone and rifampicin.
Multibacillary:


• More numerous and irregular;
• Peripheral nerve involvement with
• Weakness and loss of sensation is
 common.
• It is associated with symmetric skin lesions,
  nodules, plaques, thickened dermis

• frequent involvement of the nasal mucosa
  resulting in nasal congestion and epistaxis .
 Drugs Used in
  Leprosy
Dapsone & Other Sulfones

• Diaminodiphenylsulfone – Dapsone.

• It inhibits folate synthesis.

• Acedapsone – repository formulation.
• Resistance :
• Monotherapy – leads to resistance in a large
  population.
• Primary resistance
• Multi drug therapy - combination of dapsone,
  rifampin, and clofazimine is recommended for
  initial therapy .
Pharmacokinetics
• Well absorbed from the gut
• Dapsone's half-life is 1–2 days
• Skin heavily infected with M leprae may contain
  several times more drug than normal skin.
• In renal failure, the dose have to be adjusted.
• The usual adult dosage in leprosy is 100 mg daily.
  For children, the dose is proportionately less
Clinical uses
• Used in leprosy – multi drug regimen.
• Dapsone used to prevent and treat Pneumocystis
  jiroveci pneumonia in AIDS patients.


  Toxicity
 Hemolysis
Methemoglobinemia
Gastrointestinal intolerance, fever, pruritus, and
 various rashes occur
erythema nodosum leprosum
Rifampin
• Rifampin in a dosage of 600 mg daily is highly
  effective in lepromatous leprosy.
• The drug is given in combination with dapsone
  or another antileprosy drug.
• A single monthly dose of 600 mg may be
  beneficial in combination therapy
Mechanism of action
• Binds to the subunit of bacterial DNA-dependent
  RNA polymerase .
• Thereby inhibits RNA synthesis

• Bactericidal for mycobacteria .
• Penetrates most tissues and penetrates into
  phagocytic cells
Resistance
• Several possible point mutations in rpoB

• Reduced binding of rifampin to RNA polymerase
 Pharmacokinetics
• Well absorbed after oral administration
• Excreted mainly through the liver into bile
• Enterohepatic recirculation
• Bulk excreted as a deacylated metabolite in feces
  and a small amount in the urine
• C.S.F. levels – adequate in meningeal infection.
Clinical Uses
• Mycobacterial Infections :
• In combination with other agents, leprosy.
• Tuberculosis – in combination with isoniazid.
eliminate meningococcal carriage
prophylaxis in contacts of children with
  Haemophilus influenzae type b disease
 eradicate staphylococcal carriage
Adverse Reactions

• Rashes, thrombocytopenia, and nephritis
• Cholestatic jaundice , occasionally hepatitis
• Light-chain proteinuria
• Flu-like syndrome - fever, chills, myalgias,
  anemia, and thrombocytopenia; acute tubular
  necrosis – rarely .
• Imparts a harmless orange color to urine, sweat,
  tears, and contact lenses .
• Induces most cytochrome P450 isoforms -
  increases the elimination of numerous other
  drugs
Clofazimine

• Phenazine dye - alternative to dapsone

• Absorption - from the gut is variable
• Major portion of the drug is excreted in feces
• Stored widely in reticuloendothelial tissues and
  skin
• Serum half-life may be 2 months
• Sulfone-resistant leprosy or when patients are
  intolerant to sulfones .
• A common dosage is 100 mg/d orally.
• Skin discoloration ranging from red-brown to
  nearly black.
• Gastrointestinal intolerance occurs occasionally.
Multidrug therapy
• Dapsone resistance  multidrug therapy.
• Rifampin, dapsone and clofazimine – introduced
  by the WHO .
• Advantages :
• Effective in cases with dapsone resistance.
• Prevents emergence of dapsone resistance.
• Affords quick symptom relief and renders MBL
  cases noncontagious.
• Reduces total duration of therapy.
Drugs         Multibacillary      Paucibacillary
Rifampin      600mg once a        600 mg once a
              month .             month .
Dapsone       100mg daily self    100 mg daily self
              administered        administered.
Clofazimine   300mg once a            -
              month

              50 mg. daily self
              administered.
Duration      12 months           6 months

				
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posted:12/1/2011
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Description: Pharmacology of Drugs used in Infectious Diseases