Leprosy Pharm

Question 1

What are the treatment recommendations for tuberculoid leprosy?

Answer 1

dapsone 100 mg daily and rifampicin 600 mg daily for 12 months then discontinue

Question 2

What are the treatment recommendations for lepromatous leprosy?

Answer 2

dapsone 100 mg daily, rifampicin 600 mg daily, AND clofazimine 50 mg daily for 24 months then discontinue

Question 3

How does dapsone work?

Answer 3

folate antagonist that competitely binds against PABA to bacteral dihydropteroate synthease

also inhibits second messenger pathways involve din neutrophil chemotaxis

Question 4

The metabolism of dapsone makes it a prime candidate for toxicity. What are some of the byproducts and their associated toxicity?

Answer 4

hydroxylamine- gives rise to hemolysis and methemoglobinemia (O2 sats can fall, with blue lips and nail beds)

Question 5

DD interactions of dapsone?

Answer 5

• rifampin
• drugs for gastric hyperacidity (cimetidine and omeprazole)
• trimethoprim

Question 6

Contraindications of dapsone?

Answer 6

• G6PD deficiency
• renal disease (will cause accumulation)

Question 7

What is dapsone (sulfone) hypersensitivity syndrome?

Answer 7

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

Question 8

What is another characteristic sign of dapsone syndrome?

Answer 8

a maculopapular rash confined to either the upper limbs or the forehead (SJS reported rarely)

Question 9

What else is dapsone used for?

Answer 9

• acne vulgaris
• dermatitis herpetiformis

and others off-label

Question 10

How does rifampin work?

Answer 10

inhibits DNA-dependent RNA polymerase

Question 11

Points of interest with rifampin?

Answer 11

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

CYP inducer

Question 12

AEs of rifampin?

Answer 12

• transient LFT increase
• can discolor bodily fluids (urine, saliva, tears, sputum and contact lens)
• makes diabetes management harder

Question 13

How does clofazimine work?

Answer 13

binds to mycobacterial DNA, specifically guanine and cytosine with some level of specificity due to increased presence of these bases in the bacteria

Question 14

AEs of Clofazimine?

Answer 14

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)

Question 15

Metabolism of clofazimine?

Answer 15

hepatic, unchanged (hepatitis and juandice reported)

Question 16

Question 17

What are some drugs used if clofazimine is not well-tolerated?

Answer 17

• clarithromycin
• minocycline
• ofloxacin

Question 18

How does clarithromycin work? Minocycline?

Answer 18

Clarithromycin- inhibits 50S subunit

Minocycline- inhibits 30S subunit

Question 19

Question 20

How does thalidomide work?

Answer 20

inhibits NFkB mediated transcriptional upregulation and TNF-a production and acts as an anti-inflammatory

Question 21

AEs of Thalidomide?

Answer 21

• teratrogenic
• somnolence, rash
• rarely peripheral neuropathy

Question 22

Contraindications for thalidomide?

Answer 22

HIV- can increase viral load