Chapter 187- Dapsone

Question 1

Side effects for dapsone frequently observed in G6PD patients (2)

Answer 1

Hemolysis

Methemoglobinemia

Question 2

MOA of dapsone

Answer 2

1. Inhibits the synthesis of dihydrofolic acid by competing with PABA for active site of dihydropteroate synthetase
2. Inhibits neutrophil chemotaxis
3. Inhibits release of IL8, PGD2, and TNF alpha
4. Inhibits myeloperoxidase - hydrogen peroxide - halide mediated cytotoxic system

Question 3

PCP prophylaxis in immunocompromised patients

Answer 3

Pyrimethamine + Leucovorin + Dapsone

Question 4

Uses of dapsone for anrimicrobial (5)

Answer 4

Hansen disease
Actinomycetoma
Rhinosporidiosis
Malaria
Toxoplasmosis

Question 5

FDA approved for acne

Answer 5

7.5% dapsone gel OD

Question 6

Enzyme in azurophilic granules of neutrophils and in the lysosomes of monocytes that catalyzes conversion of hydrogen peroxide and chloride ions into hypochlorous acid

Answer 6

Myeloperoxidase

Question 7

Metabolites of dapsone (2)

Answer 7

1. MADDS by N-acetyltransferase
   (Monoacetyl dapsone)
2. DDS NOH by cytochrome P450 enzymes
   (Dapsone hydroxylamine)

Question 8

Half life of dapsone

Answer 8

30 hours

Question 9

2 metabolic pathways of dapsone

Answer 9

Acetylation

N hydroxylation

Question 10

Dapsone efficacy, half life, and toxicitieesappear unrelated to rate of acetylation.
True or False

Answer 10

True

Question 11

Dapsone hydroxylamine can be reduced back to dapsone via (2)

Answer 11

1. MetHgb reductase in RBCs

2. Cytochrome b5 reductase in hepatocytes

Question 12

Increases blood levels of dapsone

Answer 12

Probenecid

Trimethoprim

Question 13

Reduced blood levels of Dapsone

Answer 13

Rifampicin

Question 14

Blocks hydroxylation of dapsone

Answer 14

Cimetidine 400 mg TID

Omeprazole

Question 15

Dapsone is contraindicated in

Answer 15

Patients with renal dysfunction

Question 16

Uses of dapsone for antiinflammatory action

Answer 16

DH
EED
LAD
CBDC
Bullous SLE

Question 17

As unifying feature most diseases treated with dapsone have ___ as predominant infiltrating cell.

Answer 17

Granulocytes (neutrophils/eosinophils)

Question 18

Topical dapsone + BPO results in

Answer 18

Yellow orange discoloration of the skin

Question 19

MC side effect of dapsone

Answer 19

Dose-related hemolysis

Question 20

Consequence of dapsone hydrocylamine generation of ROS

Answer 20

Methemoglobinemia

Question 21

Methemoglobinemia becomes symptomatic when ___% of metHgb is present

Answer 21

20-30%

Question 22

Screening test for methemoglobinemia

Answer 22

Pulse oximetry

Question 23

Antidote for metHgbinemia

Answer 23

Cimetidine 400mg TID

Lipoic acid 90mg OD

Question 24

Dapsone induced photosensitivity is dose dependent. True or False

Answer 24

False, not

Question 25

Triad of dapsone hypersensitivity syndrome

Answer 25

Fever Rash (exfoliative dermatitis) Hepatitis

Question 26

Dapsone hypersensitivity syndrome occurs within first ___ weeks of therapy

Answer 26

6 weeks

Question 27

Most frequent COD of dapsone hypersensitivity syndrome

Answer 27

Hepatic coma (10%)

Question 28

Early DC of dapsone is associated with good prognosis. | True or False

Answer 28

True

Question 29

Etiologic agent of DHS (3)

Answer 29

HHV6 CMV EBV

Question 30

Treatment for DHS

Answer 30

Plasma exchange

Question 31

Oxidized Hgb becomes visible as __

Answer 31

Heinz bodies

Question 32

Responsible for reversing oxidative damage within RBC

Answer 32

Glutathione

Question 33

If dapsone therapy is efficacious but hemolysis is limiting therapy, coadministration of ___ may allow continuation of drug at therapeutic doses

Answer 33

Darbopoietin

Question 34

Rare idiosyncratic side effect that occurs during first __ months of therapy

Answer 34

3

Question 35

Symptoms of agranulocytosis (4)

Answer 35

Fever Pharyngitis Dysphagia Oral ulcerations

Question 36

Treatment for agranulocytosis

Answer 36

Recombinant GCSF

Question 37

Before initiation of therapy, the ff should be ordered (5)

Answer 37

``` G6PD CBC Reticulocyte count Hepatic function tests Renal function tests ```

Question 38

During therapy, the ff should be requested

Answer 38

CBC weekly for the first month, 2x a month for next 2 months | Reticulocyte count weekly for the first month, 2x a month for next 2 months

Question 39

Drug in hgb level of __ should be expected and does not warrant dc of drug

Answer 39

1-2g/dl

Question 40

Dapsone causes falsely high HbA1c levels due to accelerated RBC turnover, hence monitor fructosamine levels instead. True or False

Answer 40

False, low.

Question 41

Used with caution in the ff: (5)

Answer 41

``` G6PD deficiency MetHgb reductase deficiency Severe hepatopathy Cardiac insufficiency or heart failure Pulmonary diseases ```

Question 42

Hemolysis may be delayed up to ___ due to enterohepatic recirculation

Answer 42

9 days

Question 43

Massive IV hemolysis in dapsone overdose has been linked to

Answer 43

Optic ischemic injury

Question 44

Treatment for dapsone overdose (3)

Answer 44

Dialysis Activated charcoal Methylene blue 1% solution 1-2 mg/kg slow IV (CI: G6PD patients) Ascorbic acid 1000 mg IV q 12 hours