Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dapsone (DDS) has for about 4 decades been the most important antileprosy drug. Concentrations of dapsone and its monoacetyl metabolite, MADDS, can be determined in biological media by high-performance liquid chromatography. After oral administration, the drug is slowly absorbed, the maximum concentration in plasma being reached at about 4 hours, with an absorption half-life of about 1.1 hours. However, the extent of absorption has not been adequately determined. The elimination half-life of dapsone is about 30 hours. The drug shows linear pharmacokinetics within the therapeutic range and the time-course after oral administration fits a 2-compartment model. The concentration-time profile of dapsone after parenteral administration is reviewed. Of clinical importance is the development of a new long acting injection, which permits monthly supervised administration as recommended by the World Health Organization. Following dapsone injection in gluteal subcutaneous adipose tissue, a sufficiently sustained absorption for this purpose has been reported. Dapsone is about 70 to 90% protein bound and its monoacetylated metabolite (MADDS) is almost completely protein bound. The volume of distribution of dapsone is estimated to be 1.5 L/kg. It is distributed in most tissues, but M. leprae living in the Schwann cells of the nerves might be unaffected. Dapsone crosses the placenta and is excreted in breast milk and saliva. Dapsone is extensively metabolised. Dapsone, some MADDS and their hydroxylated metabolites are found in urine, partly conjugated as N-glucuronides and N-sulphates. The acetylation ratio (MADDS:dapsone) shows a genetically determined bimodal distribution and allows the definition of 'slow' and 'rapid' acetylators. As enterohepatic circulation occurs, the elimination half-life of dapsone is markedly decreased after oral administration of activated charcoal. This permits successful treatment in cases of intoxication. The daily dose of dapsone in leprosy is 50 to 100mg, but varies from 50 to 400mg in the treatment of other dermatological disorders. In malaria prophylaxis, a weekly dose of 100mg is used in combination with pyrimethamine. Side effects are mostly not serious below a daily dose of 100mg and are mainly haematological effects. The dapsone therapeutic serum concentration range can be defined as 0.5 to 5 mg/L. Alcoholic liver disease decreases the protein binding of dapsone; coeliac disease and dermatitis herpetiformis may delay its oral absorption and severe leprosy has been reported to affect the extent of absorption.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Clinical pharmacokinetics of dapsone. 353 May 84

Dapsone is used to treat several systemic inflammatory diseases, many of which have head and neck manifestations, such as leprosy, systemic lupus erythematosus, rhinosporidiosis, relapsing polychondritis, dermatitis herpetiformis, pemphigus vulgaris and bullous pemphigoid. It has also been recently used prophylactically alone or in combination against malaria and in AIDS patients against Pneumocystis carinii infections. This is significant to the otolaryngologist-head and neck surgeon since approximately 40% of AIDS patients will have head and neck manifestations. Thus, the likelihood that otolaryngologists will be treating patients who are taking dapsone regularly is significant. We present a case of a 16-year-old female who presented with a presumptive diagnosis of discoid lupus for biopsy confirmation of her disease. Induction of general anesthesia was complicated by methemoglobinemia, an uncommon side effect of dapsone. We will discuss recognition and prevention of this side effect, its potential anesthetic implications, complications and treatment.
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PMID:Dapsone-induced methemoglobinemia: an anesthetic risk. 755 44

Agranulocytosis is a rare, severe and unpredictable idiosyncratic reaction associated with drug therapy that can lead to life-threatening illness. Typically, the patient presents with a fever and evidence of infection 1-3 months after initiation of drug administration with a neutrophil count below 0.5x10(9) l. Of the drugs linked with this disease, aminopyrine, dipyrone, clozapine, anti-thyroid agents, sulphonamides and dapsone are the best documented. Generally, agranulocytosis is associated with older individuals (>60 years) and those of non-Caucasian descent. The incidence of agranulocytosis in subjects taking oral dapsone in combination with maloprim for malaria is 1 -- 10-20,000 while leprosy patients treated with dapsone exhibit virtually zero risk of agranulocytosis. However, dapsone is unusual in that during the rare but severe inflammatory disease, dermatitis herpetiformis (DH), the risk of agranulocytosis is multiplied between 25 and 33 fold compared with normal patients. It is conceivable that dapsone might exhibit a similar risk in coeliac disease, a condition related to DH. As dapsone plasma levels in DH subjects can be high (2-10 microg/ml) the increased risk of agranulocytosis could be related to drug dosage, or increased immune responsiveness. The high risks in DH patients probably necessitate monitoring of neutrophil cell population in the first 3 months of therapy, while topical usage of the drug in acne treatment in otherwise healthy patients predominantly below the age of 25 is at the opposite end of the risk scale, probably as low as 1 in 10-20,000 patients.
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PMID:Dapsone-mediated agranulocytosis: risks, possible mechanisms and prevention. 1131 58

Drug induced agranulocytosis is a rare condition. Yet one hundred and five drugs have been claimed to be associated with agranulocytosis and this list has since been updated. Some drugs are associated with relatively high risk. Dapsone is one of the drugs that was associated with a sufficiently high incidence of fatal agranulocytosis. It was withdrawn from use as prophylaxis against malaria. Here we present a case of a 27 years old female who had suffered from agranulocytosis after taking Dapsone, Amitriptyline and Oflacin for treatment of Dermatitis Herpetiformis.
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PMID:Agranulocytosis--a case report. 1150 74

Dapsone is a leprostatic agent commonly prescribed for the treatment of patients with leprosy, malaria, and a variety of blistering skin diseases, including dermatitis herpetiformis. Methemoglobinemia, a potentially life-threatening condition in which the oxygen-carrying capacity of blood in body tissues is reduced, is a known adverse effect of dapsone use. The authors report a case of dapsone-induced methemoglobinemia observed in the emergency department during routine workup for contact dermatitis in a patient with celiac disease. The pathophysiologic mechanisms, diagnosis, and management of dapsone-induced methemoglobinemia are discussed.
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PMID:Pathophysiologic mechanisms, diagnosis, and management of dapsone-induced methemoglobinemia. 2009 49