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Rifampicin
Introduction
• Rifamycins are a family of antibiotics, with the first agent, rifamycin V, derived in 1957 in
Italy, from the soil mold Amycolaptis rifamycinica (formerly Streptomyces mediterranei)
• In 1959, a more stable semisynthetic rifamycin, ‘rifampicin’ was discovered.
Rifampicin Rifampin
• Rifampin, rifabutin rifapentine, and rifaximin are rifamycins that are currently available
• Rifampin was released in 1967 and is the most commonly used ‘rifamycin’ in
dermatology
Pharmacokinetics
• Quickly and completely absorbed on oral administration especially if stomach is
empty
• With an oral dose of 600mg, a peak level in serum(6-8 µg/ml) is reached in 2-3
hours
• MIC is 0.1-0.3 µg/ml (45-70 times of MIC)
• Half – life ≈ 3-4 hours
• Nearly 80-90% of drug remains bound to plasma proteins and is not available for
killing of bacilli
Metabolites are
excreted in bile
Rapidly metabolized in liver through
deacetylation and oxidation
Excreted Metabolites
reabsorbed
Prolongs drug action
Fraction excreted
through kidney
• Rifampicin is able to cross the BBB and Placenta
• Because of its affinity for lipids, it crosses cell membranes and effective in killing
intracellular bacilli
Mechanism of Action
Prevents mRNA synthesis
&
Protein synthesis
Therapeutic effects
• Exceptionally bactericidal against M. leprae
• A single dose of 1500 mg or 3 to 4 daily doses of 600mg kills 99.9% or more of viable
organisms
• However, the rate of killing is not proportionately enhanced by subsequent doses
• Rifampicin may exert a delayed antibiotic effect for several days, during which the
organism's multiplication is inhibited
• Drug is equally effective against both the Dapsone sensitive and resistant organisms
• High bactericidal activity of rifampicin rationale for single monthly dose, which is
cost-effective for leprosy-control programs
• Monthly supervised single dose 600mg
• The clinical effects of drug are very rapid
• In lepromatous patients, the nasal symptoms regress within 2-3 weeks
• Skin lesion/infiltration begin to clear in 2-3 months
Adverse Effects
• Harmless orange-red colour to urine, sweat, tears, and contact lens
• Loss of appetite, nausea, vomiting & pain abdomen
• Cholestatic jaundice and occasional hepatitis
• Occasionally rashes, thrombocytopenia and nephritis
• Safe in pregnancy and lactation
• Given in third trimester, it may result in increased risk of bleeding in new born
• CYP inducer: less pronounced effect when given monthly
Rifampicin Resistance
• Due to mutation in rpoB gene (codon 531: TCG to TTC)
• Substitutions within codon Ser456 have been shown to be most frequent mutations
associated with development of rifampicin-resistant phenotype in M. leprae
Other uses
• Other Mycobacterial infections
M. Tuberculosis
M. marinum
M. avium-intracellulare complex
• MSSA and MRSA infections
• Bartonella infections, Rhinoscleroma, Cutaneous leishmaniasis, aspergillosis,
brucellosis, tularemia, chlamydial infections and gonorrhea
• Psoriasis : Controversial role
• Pruritus of Primary biliary cirrhosis
Thank You

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Rifampicin in leprosy

  • 2. Introduction • Rifamycins are a family of antibiotics, with the first agent, rifamycin V, derived in 1957 in Italy, from the soil mold Amycolaptis rifamycinica (formerly Streptomyces mediterranei) • In 1959, a more stable semisynthetic rifamycin, ‘rifampicin’ was discovered. Rifampicin Rifampin
  • 3. • Rifampin, rifabutin rifapentine, and rifaximin are rifamycins that are currently available • Rifampin was released in 1967 and is the most commonly used ‘rifamycin’ in dermatology
  • 4. Pharmacokinetics • Quickly and completely absorbed on oral administration especially if stomach is empty • With an oral dose of 600mg, a peak level in serum(6-8 µg/ml) is reached in 2-3 hours • MIC is 0.1-0.3 µg/ml (45-70 times of MIC) • Half – life ≈ 3-4 hours
  • 5. • Nearly 80-90% of drug remains bound to plasma proteins and is not available for killing of bacilli
  • 6. Metabolites are excreted in bile Rapidly metabolized in liver through deacetylation and oxidation Excreted Metabolites reabsorbed Prolongs drug action Fraction excreted through kidney
  • 7. • Rifampicin is able to cross the BBB and Placenta • Because of its affinity for lipids, it crosses cell membranes and effective in killing intracellular bacilli
  • 8. Mechanism of Action Prevents mRNA synthesis & Protein synthesis
  • 9. Therapeutic effects • Exceptionally bactericidal against M. leprae • A single dose of 1500 mg or 3 to 4 daily doses of 600mg kills 99.9% or more of viable organisms • However, the rate of killing is not proportionately enhanced by subsequent doses • Rifampicin may exert a delayed antibiotic effect for several days, during which the organism's multiplication is inhibited • Drug is equally effective against both the Dapsone sensitive and resistant organisms
  • 10. • High bactericidal activity of rifampicin rationale for single monthly dose, which is cost-effective for leprosy-control programs • Monthly supervised single dose 600mg • The clinical effects of drug are very rapid • In lepromatous patients, the nasal symptoms regress within 2-3 weeks • Skin lesion/infiltration begin to clear in 2-3 months
  • 11. Adverse Effects • Harmless orange-red colour to urine, sweat, tears, and contact lens • Loss of appetite, nausea, vomiting & pain abdomen • Cholestatic jaundice and occasional hepatitis • Occasionally rashes, thrombocytopenia and nephritis
  • 12. • Safe in pregnancy and lactation • Given in third trimester, it may result in increased risk of bleeding in new born • CYP inducer: less pronounced effect when given monthly
  • 13. Rifampicin Resistance • Due to mutation in rpoB gene (codon 531: TCG to TTC) • Substitutions within codon Ser456 have been shown to be most frequent mutations associated with development of rifampicin-resistant phenotype in M. leprae
  • 14. Other uses • Other Mycobacterial infections M. Tuberculosis M. marinum M. avium-intracellulare complex • MSSA and MRSA infections • Bartonella infections, Rhinoscleroma, Cutaneous leishmaniasis, aspergillosis, brucellosis, tularemia, chlamydial infections and gonorrhea • Psoriasis : Controversial role • Pruritus of Primary biliary cirrhosis