What are the treatment recommendations for tuberculoid leprosy?
dapsone 100 mg daily and rifampicin 600 mg daily for 12 months then discontinue
What are the treatment recommendations for lepromatous leprosy?
dapsone 100 mg daily, rifampicin 600 mg daily, AND clofazimine 50 mg daily for 24 months then discontinue
How does dapsone work?
folate antagonist that competitely binds against PABA to bacteral dihydropteroate synthease
also inhibits second messenger pathways involve din neutrophil chemotaxis
The metabolism of dapsone makes it a prime candidate for toxicity. What are some of the byproducts and their associated toxicity?
hydroxylamine- gives rise to hemolysis and methemoglobinemia (O2 sats can fall, with blue lips and nail beds)
DD interactions of dapsone?
-drugs for gastric hyperacidity (cimetidine and omeprazole)
Contraindications of dapsone?
-renal disease (will cause accumulation)
What is dapsone (sulfone) hypersensitivity syndrome?
syndrome associated with many possible symptoms including hemolysis (correctable), methemoglobinemia, hepatitis, jaundice, psychosis, peripheral neuropathy, leukopenia, and sver hypoalbuminemia
LFTs will correct after stopping drug
What is another characteristic sign of dapsone syndrome?
a maculopapular rash confined to either the upper limbs or the forehead (SJS reported rarely)
What else is dapsone used for?
and others off-label
How does rifampin work?
inhibits DNA-dependent RNA polymerase
Points of interest with rifampin?
It is hepatically metabolized, disseminates widely in the body and there is easy passage through the placenta, meninges, and into breast milk as well, and undergoes entero-hepatic recirculation
AEs of rifampin?
-transient LFT increase
-can discolor bodily fluids (urine, saliva, tears, sputum and contact lens)
-makes diabetes management harder
How does clofazimine work?
binds to mycobacterial DNA, specifically guanine and cytosine with some level of specificity due to increased presence of these bases in the bacteria
AEs of Clofazimine?
progressive, dose-dependent anti-inflammatory and immunosuppression that is predominantly localized to skin and peripheral nerves
-skin discoloration (may trigger depression)
-staining of body and body fluids (sweat, tears, urine, bowel) (feces look black or tarry)
Metabolism of clofazimine?
hepatic, unchanged (hepatitis and juandice reported)
What are some drugs used if clofazimine is not well-tolerated?
How does clarithromycin work? Minocycline?
Clarithromycin- inhibits 50S subunit
Minocycline- inhibits 30S subunit
How does thalidomide work?
inhibits NFkB mediated transcriptional upregulation and TNF-a production and acts as an anti-inflammatory
AEs of Thalidomide?
-rarely peripheral neuropathy
Contraindications for thalidomide?
HIV- can increase viral load