Chapter 187- Dapsone Flashcards

1
Q

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

A

Hemolysis

Methemoglobinemia

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2
Q

MOA of dapsone

A
  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
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3
Q

PCP prophylaxis in immunocompromised patients

A

Pyrimethamine + Leucovorin + Dapsone

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4
Q

Uses of dapsone for anrimicrobial (5)

A
Hansen disease
Actinomycetoma
Rhinosporidiosis
Malaria
Toxoplasmosis
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5
Q

FDA approved for acne

A

7.5% dapsone gel OD

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6
Q

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

A

Myeloperoxidase

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7
Q

Metabolites of dapsone (2)

A
  1. MADDS by N-acetyltransferase
    (Monoacetyl dapsone)
  2. DDS NOH by cytochrome P450 enzymes
    (Dapsone hydroxylamine)
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8
Q

Half life of dapsone

A

30 hours

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9
Q

2 metabolic pathways of dapsone

A

Acetylation

N hydroxylation

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10
Q

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

A

True

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11
Q

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

A
  1. MetHgb reductase in RBCs

2. Cytochrome b5 reductase in hepatocytes

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12
Q

Increases blood levels of dapsone

A

Probenecid

Trimethoprim

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13
Q

Reduced blood levels of Dapsone

A

Rifampicin

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14
Q

Blocks hydroxylation of dapsone

A

Cimetidine 400 mg TID

Omeprazole

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15
Q

Dapsone is contraindicated in

A

Patients with renal dysfunction

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16
Q

Uses of dapsone for antiinflammatory action

A
DH
EED
LAD
CBDC
Bullous SLE
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17
Q

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

A

Granulocytes (neutrophils/eosinophils)

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18
Q

Topical dapsone + BPO results in

A

Yellow orange discoloration of the skin

19
Q

MC side effect of dapsone

A

Dose-related hemolysis

20
Q

Consequence of dapsone hydrocylamine generation of ROS

A

Methemoglobinemia

21
Q

Methemoglobinemia becomes symptomatic when ___% of metHgb is present

A

20-30%

22
Q

Screening test for methemoglobinemia

A

Pulse oximetry

23
Q

Antidote for metHgbinemia

A

Cimetidine 400mg TID

Lipoic acid 90mg OD

24
Q

Dapsone induced photosensitivity is dose dependent. True or False

A

False, not

25
Q

Triad of dapsone hypersensitivity syndrome

A

Fever
Rash (exfoliative dermatitis)
Hepatitis

26
Q

Dapsone hypersensitivity syndrome occurs within first ___ weeks of therapy

A

6 weeks

27
Q

Most frequent COD of dapsone hypersensitivity syndrome

A

Hepatic coma (10%)

28
Q

Early DC of dapsone is associated with good prognosis.

True or False

A

True

29
Q

Etiologic agent of DHS (3)

A

HHV6
CMV
EBV

30
Q

Treatment for DHS

A

Plasma exchange

31
Q

Oxidized Hgb becomes visible as __

A

Heinz bodies

32
Q

Responsible for reversing oxidative damage within RBC

A

Glutathione

33
Q

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

A

Darbopoietin

34
Q

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

A

3

35
Q

Symptoms of agranulocytosis (4)

A

Fever
Pharyngitis
Dysphagia
Oral ulcerations

36
Q

Treatment for agranulocytosis

A

Recombinant GCSF

37
Q

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

A
G6PD
CBC
Reticulocyte count
Hepatic function tests
Renal function tests
38
Q

During therapy, the ff should be requested

A

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

39
Q

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

A

1-2g/dl

40
Q

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

True or False

A

False, low.

41
Q

Used with caution in the ff: (5)

A
G6PD deficiency
MetHgb reductase deficiency
Severe hepatopathy
Cardiac insufficiency or heart failure
Pulmonary diseases
42
Q

Hemolysis may be delayed up to ___ due to enterohepatic recirculation

A

9 days

43
Q

Massive IV hemolysis in dapsone overdose has been linked to

A

Optic ischemic injury

44
Q

Treatment for dapsone overdose (3)

A

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