Chapter 187- Dapsone Flashcards
Side effects for dapsone frequently observed in G6PD patients (2)
Hemolysis
Methemoglobinemia
MOA of dapsone
- Inhibits the synthesis of dihydrofolic acid by competing with PABA for active site of dihydropteroate synthetase
- Inhibits neutrophil chemotaxis
- Inhibits release of IL8, PGD2, and TNF alpha
- Inhibits myeloperoxidase - hydrogen peroxide - halide mediated cytotoxic system
PCP prophylaxis in immunocompromised patients
Pyrimethamine + Leucovorin + Dapsone
Uses of dapsone for anrimicrobial (5)
Hansen disease Actinomycetoma Rhinosporidiosis Malaria Toxoplasmosis
FDA approved for acne
7.5% dapsone gel OD
Enzyme in azurophilic granules of neutrophils and in the lysosomes of monocytes that catalyzes conversion of hydrogen peroxide and chloride ions into hypochlorous acid
Myeloperoxidase
Metabolites of dapsone (2)
- MADDS by N-acetyltransferase
(Monoacetyl dapsone) - DDS NOH by cytochrome P450 enzymes
(Dapsone hydroxylamine)
Half life of dapsone
30 hours
2 metabolic pathways of dapsone
Acetylation
N hydroxylation
Dapsone efficacy, half life, and toxicitieesappear unrelated to rate of acetylation.
True or False
True
Dapsone hydroxylamine can be reduced back to dapsone via (2)
- MetHgb reductase in RBCs
2. Cytochrome b5 reductase in hepatocytes
Increases blood levels of dapsone
Probenecid
Trimethoprim
Reduced blood levels of Dapsone
Rifampicin
Blocks hydroxylation of dapsone
Cimetidine 400 mg TID
Omeprazole
Dapsone is contraindicated in
Patients with renal dysfunction
Uses of dapsone for antiinflammatory action
DH EED LAD CBDC Bullous SLE
As unifying feature most diseases treated with dapsone have ___ as predominant infiltrating cell.
Granulocytes (neutrophils/eosinophils)
Topical dapsone + BPO results in
Yellow orange discoloration of the skin
MC side effect of dapsone
Dose-related hemolysis
Consequence of dapsone hydrocylamine generation of ROS
Methemoglobinemia
Methemoglobinemia becomes symptomatic when ___% of metHgb is present
20-30%
Screening test for methemoglobinemia
Pulse oximetry
Antidote for metHgbinemia
Cimetidine 400mg TID
Lipoic acid 90mg OD
Dapsone induced photosensitivity is dose dependent. True or False
False, not
Triad of dapsone hypersensitivity syndrome
Fever
Rash (exfoliative dermatitis)
Hepatitis
Dapsone hypersensitivity syndrome occurs within first ___ weeks of therapy
6 weeks
Most frequent COD of dapsone hypersensitivity syndrome
Hepatic coma (10%)
Early DC of dapsone is associated with good prognosis.
True or False
True
Etiologic agent of DHS (3)
HHV6
CMV
EBV
Treatment for DHS
Plasma exchange
Oxidized Hgb becomes visible as __
Heinz bodies
Responsible for reversing oxidative damage within RBC
Glutathione
If dapsone therapy is efficacious but hemolysis is limiting therapy, coadministration of ___ may allow continuation of drug at therapeutic doses
Darbopoietin
Rare idiosyncratic side effect that occurs during first __ months of therapy
3
Symptoms of agranulocytosis (4)
Fever
Pharyngitis
Dysphagia
Oral ulcerations
Treatment for agranulocytosis
Recombinant GCSF
Before initiation of therapy, the ff should be ordered (5)
G6PD CBC Reticulocyte count Hepatic function tests Renal function tests
During therapy, the ff should be requested
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
Drug in hgb level of __ should be expected and does not warrant dc of drug
1-2g/dl
Dapsone causes falsely high HbA1c levels due to accelerated RBC turnover, hence monitor fructosamine levels instead.
True or False
False, low.
Used with caution in the ff: (5)
G6PD deficiency MetHgb reductase deficiency Severe hepatopathy Cardiac insufficiency or heart failure Pulmonary diseases
Hemolysis may be delayed up to ___ due to enterohepatic recirculation
9 days
Massive IV hemolysis in dapsone overdose has been linked to
Optic ischemic injury
Treatment for dapsone overdose (3)
Dialysis
Activated charcoal
Methylene blue 1% solution 1-2 mg/kg slow IV (CI: G6PD patients)
Ascorbic acid 1000 mg IV q 12 hours