Leprosy

Question 1

What drugs are given to patients that cannot tolerate clofazimine?

Answer 1

clarithromycin; minocycline; ofloxacin

Question 2

What is the standard Tx for tuberculoid leprosy?

Answer 2

dapsone and rifampicin for 12 months then D/C therapy

Question 3

Standard Tx for lepromatous leprosy?

Answer 3

Dapsone, rifampicin, clofazimine for 24 months then D/C therapy

Question 4

What is an inactive metabolite of dapsone metabolism?

Answer 4

hydroxylamine (potent oxidant)

Question 5

What will the production of hydroxylamine cause?

Answer 5

methemoglobinemia and hemolysis

Question 6

Dapsone interaction with rifampin will lead to what?

Answer 6

increased toxicity

Question 7

dapsone interaction with cimetidine and omeprazole will cause what?

Answer 7

decrease in toxicity

Question 8

dapsone and trimethoprim lead to what?

Answer 8

increased in serum levels of both drugs

Question 9

How is dapsone eliminated?

Answer 9

renal (renal fxn important)

Question 10

What does the interaction of probenecid and dapsone have with elimination?

Answer 10

decreases clearance with renal tubular secretion

Question 11

What are the MOAs of dapsone?

Answer 11

1) folate antagonsist producing bacteriostatic effect; 2) inhibitor of 2nd msg path involved in neutrophil chemotaxis

Question 12

What can dapsone syndrome lead to?

Answer 12

hemolysis; methemoglobinemia; hepatitis; cholestatic jaundice; peripheral neuropathy; severe hypoalbuminemia; psychosis; leukopenia; agranulocytosis

Question 13

How does dapsone syndrome clinically present?

Answer 13

maculopapular or exfoliative rash confined to either upper limbs or forehead

Question 14

What are the sequence of Sx associated with dapsone syndrome?

Answer 14

dermatitis; LAD along post. border of SCM; hepatitis

Question 15

What are the clinical indications for dapsone?

Answer 15

acne vulgaris; dermatitis herpetiformis; leprosy

Question 16

What is the MOA of rifampin?

Answer 16

inhibits bacterial and mycobacterial RNA synthesis via DNA dep RNA polymerase

Question 17

What type of cells are susceptible to rifampin?

Answer 17

rapidly and slowly dividing organisms

Question 18

What is the distribution of rifampin?

Answer 18

widely and crosses inflamed meninges; placenta; breast milk

Question 19

metabolism of rifampin

Answer 19

hepatic (recirculates in entero-hepatic)

Question 20

elimination of rifampin

Answer 20

hepatic

Question 21

Rifampin Effects on CYP

Answer 21

INDUCER of CYP with multiple DDI

Question 22

CYP3A induction by rifampin is variable and affected how?

Answer 22

tissue/intracellular concentration of agonists (P-gp efflux); genetic variations of P450

Question 23

What is a sometimes fatal ADE associated with rifampin?

Answer 23

transient increases in hepatic enzymes and severe hepatotoxicity

Question 24

What patients should be monitored while taking rifampin?

Answer 24

diabetics

Question 25

What are side affects that can scare the patient taking rifampin?

Answer 25

discolor of bodily fluids

Question 26

Therapy intervals are not less than 2x weekly and may present how?

Answer 26

hemolysis; hemoglobinuria; hematuria; renal tox

Question 27

MOA for clofazimine

Answer 27

preferential binding to mycobacterial guanine in DNA (non-intercalator)

Question 28

How does clofazimine improve leprosy?

Answer 28

progressive, dose dep anti-inflam & immunosuppressive

Question 29

What can clofazimine treat?

Answer 29

reversal rxns and erythema nodosum leprosum

Question 30

What is significant about the duration and make up of clofazimine?

Answer 30

highly lipophilic so months of persistence => fat and RES system

Question 31

clofazimine elimination

Answer 31

hepatic => jaundice and hepatitis

Question 32

What are alarming ADEs associated with clofazimine?

Answer 32

staining of body; body fluids; suckling infant => depression can result

Question 33

How may clofazimine look like a GI disturbance?

Answer 33

black or tarry feces

Question 34

What must always be monitored in patients taking clofazimine?

Answer 34

CBC and platelets

Question 35

What is the MOA of clarithromycin?

Answer 35

inhibits 50S ribosomal sub unit

Question 36

clarithromycin static or cidal

Answer 36

cidal

Question 37

clarithromycin and pregnancy

Answer 37

C

Question 38

MOA of minocycline

Answer 38

inhibits 30S ribosomal subunit

Question 39

minocylcine static or cidal

Answer 39

cidal

Question 40

ofloxacin MOA

Answer 40

inhibits bacterial DNA gyrase

Question 41

ofloxacin static or cidal

Answer 41

cidal

Question 42

pregnancy and minocycline

Answer 42

D

Question 43

pregnancy and ofloxacin

Answer 43

C

Question 44

Resistance to oxfloxacin, minocycline or clarithromycin

Answer 44

rare

Question 45

ADEs are associated with oxfloxacin, minocycline and clarithromycin. What are considered type 1 rxns? tx for type 1?

Answer 45

red patchy skin lesions; erythema; swollen hands/feet; joint pain Tx: corticosteroids

Question 46

What are considered type 2 rxns? Tx for type 2

Answer 46

erythema nodosum leprosum with sudden eruption of painful nodules and neuritis Tx: corticosteroids; clofazimine; thalidomide

Question 47

MOA of thalidomide

Answer 47

inhibits NFkB mediated transcriptional upregulation and TNF-a production => block leukocyte migration

Question 48

What are serious ADEs associated with thalidomide?

Answer 48

teratogen; somnolence > rash > headache; rare peripheral neuropathy

Question 49

Thalidomide and HIV patients

Answer 49

increase in plasma HIV viral load so must be monitored