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mechanism of action:
| • | bacteriostatic effect – interfere with folate synthesis pathway of bacteria |
| • | anti-inflammatory affect – inhibits lysosomal enzyme activity; may inhibit neutrophil chemotaxis (does clear the dermis of neutrophils in treated patients |
indications:
| • | two diseases that invariably respond: DH and EED |
| • | most of the other diseases that respond have granulocytes (neutrophils and eosinophils) as the predominant infiltrating cell |
| • | in general, when a pathologic lesion is characterized by a neutrophilic infiltrate and is unassociated with an infectious agent, a trial of dapsone should be considered |
| • | other "anti-neutrophil" drugs = SSKI, colchicine |
| • | infectious diseases: leprosy, PCP |
adverse effects (mainly hematologic):
| • | dapsone metabolites are potent oxidants |
| • | at 150 mg/day, hemoglobin may drop by 2g (patients with G6PD deficiency will have a greater decrease) |
| • | be careful in elderly, or in patients with cardiopulmonary problems |
| • | must closely monitor or give sulfapyridine to these patients (as a substitute) |
| • | retic count will increase |
| • | agranulocytosis (idiosyncratic) |
| • | 0.2% to 0.4% of patients treated |
| • | almost always in first 3 months of therapy |
| • | warn patients to seek immediate care if an infection develops during first several months of therapy |
| • | not a major problem in most patients (methemoglobin level usually <5%) |
| • | the cyanosis that results from methemoglobinemia may be seen in anyone with a met level >3% but may not be apparent in some patients with a level as high as 12% |
| • | can be reduced with co-administration of cimetidine |
| • | no symptoms until levels are 20% or greater |
| • | oral methylene blue for emergency reversal of methemoglobinemia |
allergy:
| • | people who are "sulfa" allergic have only a 10% cross-reactivity to sulfone's (like dapsone) |
monitoring:
| • | baseline CBC (LFT, renal function) |
| • | baseline G6PD in Asian, black or patients of Mediterranean descent |
| • | check CBC with diff ~ every 2 weeks X 3 months, then periodically |
| • | if excessive fatigue, headache, worsening cardiopulmonary symptoms --> check methemoglobin |
| • | if febrile illness --> consider agranulocytosis (check a CBC) |
| • | check for hand muscle wasting, and have patient walk on toes (screening for idiosyncratic distal motor neuropathy) |
“dapsone responsive diseases”: can think of as "anti-neutrophil"
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