PHARM: Leprosy Drugs

Question 1

What drugs are used for tuberculoid leprosy? How long?

Answer 1

Dapsone
Rifampicin

(12 months)

Question 2

What drugs are used for Lepromatous leprosy? How long?

Answer 2

Dapsone
Rifampicin
Clofazimine

(24 months)

Question 3

What is the MOA of dapsone?

Answer 3

Folate antagonist (inhibitor of second messenger pathways involved in neutrophil chemotaxis)

Question 4

Why is trimethoprim + sulfamethoxazole synergistic against some bacteria?

Answer 4

because sulfamethoxazole acts on same pathway (upstream) of trimethoprim (to prevent purine synthesis)

Question 5

What is the major side effect of dapsone?

Answer 5

Hemolysis
Methemoglobenemia
Maculopapular rash on upper limbs/forehead
Stevens-Johnson syndrome

Question 6

Who can NEVER have dapsone?

Answer 6

G6PD patients

Question 7

True or flase: the hemolysis and liver side effects of dapsone are irreversible.

Answer 7

FALSE: resolves once treatment is ended (hemolysis takes longer to reverse)

Question 8

What are the 3 labeled uses of dapsone?

Answer 8

Acne vulgaris
Dermatitis herpeiformis
Leprosy

Question 9

What is the MOA of rifampin?

Answer 9

inhibition of bacterial and mycobacterial RNA synthesis (binds to beta-subunit of DNA-dependent RNA polymerase)

Question 10

Why does rifampin have so many DDIs?

Answer 10

CYP inducer

Question 11

What are the adverse effects of rifampin?

Answer 11

Increase in hepatic enzymes

Discoloration of body fluids

Question 12

What is the MOA of clofazimine?

Answer 12

preferential binding to mycobacterial guanine in DNA (which is in higher levels than human DNA–makes selective)

Question 13

What are some adverse effects of clofazimine?

Answer 13

Staining of body/body fluids (tanning/bronzing of skin)

Staining of suckling infant

Feces black or tarry

Skin discoloration= depression and suicide

Question 14

What 3 additional drugs can be used to treat leprosy if clofazimine is contraindicated?

Answer 14

Clarithromycin
inocycline
Ofloxacin

Question 15

What is the MOA of clarithromycin?

Answer 15

inhibits 50s ribosomal subunit (bacteriocidal)

Question 16

What is the MOA of minocycline?

Answer 16

inhibits 30s ribosomal subunit (bacteriocidal)

Question 17

What is the MOA of ofloxacin?

Answer 17

inhibits bacterial DNA cyrase (bacteriocidal)

Question 18

What does a type 1 skin reaction look like?

Answer 18

red, patchy skin lesions, erythema, swollen hands/feet, joint pain

Question 19

What does a type 2 skin reaction look like?

Answer 19

Sudden eruption of numerous, painful, nodules and neuritis

Question 20

What can treat a type 1 skin reaction?

Answer 20

corticosteroids

Question 21

What can treat a type 2 skin reaction?

Answer 21

corticosteroids
clofazimine
thalidomide

Question 22

What is the MOA of thalidomide?

Answer 22

inhibition of NfKB mediated transcriptional upregulation and TNF-alpha production (to block leukocyte migration)

Question 23

What is the major adverse effect of thalidomide?

Answer 23

TERATOGEN
Somnolence > rash> h/a
Rarely peripheral neuropathy

Question 24

What is the immunological features of TT?

Answer 24

Th1 response (contain organisms in granulomas)

Question 25

What is the immunological features of LL?

Answer 25

Ineffective humoral response so mycobacteria proliferates in/around foamy macrophages

Question 26

What type of leprosy do you see erythema nodosum leprosum?

Answer 26

LL or BL

Question 27

Why does ENL occur?

Answer 27

Increase in cell mediated/humoral responses lead to systemic release of TNF and IL-4, brisk PMN influx, and Ab/Ag complex deposition)