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Dermatology Online Journal Jun 2002Dapsone (4,4'-diaminodiphenylsulfone, DDS) was synthesized a century ago and continues to be a powerful therapeutic tool in many skin diseases. We have tried to retrieve... (Review)
Review
Dapsone (4,4'-diaminodiphenylsulfone, DDS) was synthesized a century ago and continues to be a powerful therapeutic tool in many skin diseases. We have tried to retrieve and present the available knowledge and relevant information on this old but still very useful drug with the hope of encouraging and guiding practicing dermatologists to adapt it for various indications. Our objective is to familiarize the clinician with how this agent works, in what disease states it is effective, how to administer it, what adverse effects may occur, and how to monitor the patient receiving this drug.
Topics: Animals; Dapsone; Dermatologic Agents; Humans; Skin Diseases
PubMed: 12165212
DOI: No ID Found -
Drug Metabolism Reviews 1995Dapsone, an old drug introduced and used almost exclusively for the treatment of leprosy, is now utilized in an increasing number of therapeutic situations. However, its... (Review)
Review
Dapsone, an old drug introduced and used almost exclusively for the treatment of leprosy, is now utilized in an increasing number of therapeutic situations. However, its hemotoxicity is potentially severe and is often dose limiting. Effective countermeasures, based on resolution of the mechanisms underlying dapsone-induced hemotoxicity, could significantly enhance the therapeutic value of the drug. In studies on rat red cells, we have established that the N-hydroxy metabolites of dapsone, DDS-NOH and MADDS-NOH, are direct-acting hemolytic agents, that they are formed in amounts sufficient to account for the hemotoxicity of the parent drug, and that the action of these toxic metabolites in the red cell induces premature sequestration by the spleen. Incubation of rat red cells with hemolytic concentrations of arylhydroxylamines leads to the generation of hydroxyl, glutathiyl, and hemoglobinthiyl radicals, and the formation of protein-glutathione mixed disulfides. Disulfide-linked adducts are also formed between membrane skeletal proteins and hemoglobin monomers, as well as between the monomeric hemoglobin units forming dimers, trimers, tetramers, and pentamers. Profound morphological changes are seen with change from normal discoidocity to an extreme nonspherocytic enchinocyte shape. Parallel studies with human red cells indicate that the response of human cells is qualitatively similar but that there are notable differences in regard to skeletal membrane effects. A working hypothesis for the mechanism underlying dapsone hemolytic activity is proposed.
Topics: Anemia, Hemolytic; Dapsone; Erythrocytes; Hemodynamics; Humans
PubMed: 7641572
DOI: 10.3109/03602539509029818 -
The Annals of Pharmacotherapy May 1998To report a case of methemoglobinemia in a patient receiving dapsone for prophylaxis of Pneumocystis carinii pneumonia (PCP). (Review)
Review
OBJECTIVE
To report a case of methemoglobinemia in a patient receiving dapsone for prophylaxis of Pneumocystis carinii pneumonia (PCP).
CASE SUMMARY
A 69-year-old white woman was hospitalized to rule out sepsis. Two years prior to this admission, the patient received an orthotopic liver transplant after which she required hemodialysis three times weekly. Because of intolerance to trimethoprim/ sulfamethoxazole and aerosolized pentamidine, she was prescribed dapsone therapy on hospital day 13, that was continued for 11 days. On hospital day 45 the patient received a cadaveric kidney transplant, and dialysis treatments were scheduled only as needed. One week after the transplant, dapsone therapy was resumed. Nine days into this course of dapsone, the patient developed dyspnea and oxygen desaturation of unknown etiology. The patient was evaluated for and diagnosed with methemoglobinemia. She received two doses of intravenous methylene blue and one dose of oral activated charcoal due to fluctuating methemoglobin concentrations.
DISCUSSION
The elimination of dapsone is not completely understood. Several case reports of dapsone-induced methemoglobinemia are present in the literature. Most have occurred in patients who have accidentally or deliberately overdosed. Cases of methemoglobinemia in patients receiving therapeutic doses of dapsone are discussed.
CONCLUSIONS
The growing numbers of immunosuppressed patients due to transplantation of HIV may result in increased dapsone use for the prevention of PCP. Clinicians should be aware of the adverse effects associated with dapsone therapy, and patients with dyspnea and hypoxemia of unclear etiology should be evaluated for methemoglobinemia.
Topics: Aged; Anti-Infective Agents; Antibiotic Prophylaxis; Dapsone; Female; Humans; Methemoglobinemia; Pneumonia, Pneumocystis
PubMed: 9606476
DOI: 10.1345/aph.17003 -
Clinics in Dermatology 1989
Review
Topics: Cell Movement; Dapsone; Humans; Leprosy; Methemoglobinemia; Neutrophils; Skin Diseases, Vesiculobullous; Sulfanilamides; Sulfapyridine; Vasculitis
PubMed: 2680014
DOI: 10.1016/0738-081x(89)90012-6 -
Naunyn-Schmiedeberg's Archives of... Dec 2022The 4,4'-diaminodiphenyl sulfone (DDS), also known as dapsone, is traditionally used as a potent anti-bacterial agent in clinical management of leprosy. For decades,... (Review)
Review
The 4,4'-diaminodiphenyl sulfone (DDS), also known as dapsone, is traditionally used as a potent anti-bacterial agent in clinical management of leprosy. For decades, dapsone has been among the first-line medications used in multidrug treatment of leprosy recommended by the World Health Organization (WHO). Shortly after dapsone's discovery as an antibiotic in 1937, the dual function of dapsone (anti-microbial and anti-inflammatory) was elucidated. Dapsone exerts its anti-bacterial effects by inhibiting dihydrofolic acid synthesis, leading to inhibition of bacterial growth, while its anti-inflammatory properties are triggered by inhibiting reactive oxygen species (ROS) production, reducing the effect of eosinophil peroxidase on mast cells and downregulating neutrophil-mediated inflammatory responses. Among the leading mechanisms associated with its anti-microbial/anti-protozoal effects, dapsone clearly has multiple antioxidant, anti-inflammatory, and anti-apoptotic functions. In this regard, it has been described in treating a wide variety of inflammatory and infectious skin conditions. Previous reports have explored different molecular targets for dapsone and provided insight into the anti-inflammatory mechanism of dapsone. This article reviews several basic, experimental, and clinical approaches on anti-inflammatory effect of dapsone.
Topics: Humans; Dapsone; Leprosy; Anti-Inflammatory Agents; Antioxidants; Reactive Oxygen Species
PubMed: 36125533
DOI: 10.1007/s00210-022-02297-1 -
Pediatric Transplantation May 2021Dapsone has been utilized for the prevention of Pneumocystis jirovecii pneumonia in immunosuppressed patients including pediatric kidney transplant recipients, in whom...
Dapsone has been utilized for the prevention of Pneumocystis jirovecii pneumonia in immunosuppressed patients including pediatric kidney transplant recipients, in whom trimethoprim-sulfamethoxazole (TMP-SMX) is contraindicated. Dapsone adverse effects include methemoglobinemia, but there are no reports of the burden and impact of methemoglobinemia in pediatric kidney recipients that are taking dapsone for PJP prophylaxis. We conducted a retrospective chart review of all pediatric kidney recipients who had received dapsone at any time posttransplant. The indication, duration, and adverse effects of dapsone therapy were assessed. In addition, methemoglobin levels were assessed, and summary statistics performed. Data demonstrated that more than half of the patients on dapsone were not screened for methemoglobinemia. Of those screened, there was a significantly higher acquired-methemoglobinemia (77%) than previously reported in the literature. We also demonstrate significantly more anemia in patients on dapsone. Methemoglobinemia did not affect patient or graft survival and resolved with cessation of dapsone. We conclude that pediatric kidney recipients often develop methemoglobinemia and / or anemia on dapsone. We recommend if pediatric transplant recipients are prescribed dapsone, routine testing for methemoglobinemia and anemia should be done.
Topics: Anti-Infective Agents; Child; Dapsone; Female; Humans; Kidney Transplantation; Male; Methemoglobinemia; Pneumonia, Pneumocystis; Postoperative Complications; Retrospective Studies
PubMed: 33280223
DOI: 10.1111/petr.13921 -
Drugs in R&D 2002
Review
Topics: Administration, Topical; Antipruritics; Dapsone; Humans; Pruritus; Skin Diseases
PubMed: 11881527
DOI: 10.2165/00126839-200203010-00007 -
Drug Metabolism and Personalized Therapy Jul 2020Pneumocystis jirovecii pneumonia (PJP) is a potentially life-threatening infection that occurs in immunocompromised individuals. The incidence can be as high as 80% in... (Review)
Review
Pneumocystis jirovecii pneumonia (PJP) is a potentially life-threatening infection that occurs in immunocompromised individuals. The incidence can be as high as 80% in some groups but can be reduced to less than 1% with appropriate prophylaxis. HIV-infected patients with a low CD4 count are at the highest risk of PJP. Others at substantial risk include haematopoietic stem cell and solid organ transplant recipients, those with cancer (particularly haematologic malignancies), and those receiving glucocorticoids, chemotherapeutic agents, and other immunosuppressive medications. Trimethoprim-sulfamethoxazole is an established first-line line agent for prevention and treatment of PJP. However, in some situations, this medication cannot be used and dapsone is considered a suitable cost-effective second line agent. However, information on potential interactions with drugs commonly used in immunosuppressed patients is lacking or contradictory. In this this article we review the metabolic pathway of dapsone with a focus on interactions and clinical significance particularly in patients with haematological malignancies. An understanding of this process should optimise the use of this agent.
Topics: Antifungal Agents; Azoles; Dapsone; Dose-Response Relationship, Drug; Drug Interactions; Humans; Pneumonia, Pneumocystis
PubMed: 32681773
DOI: 10.1515/dmpt-2019-0018 -
Skinmed 2021
Topics: Dapsone; Dermatologic Agents; Humans
PubMed: 34861925
DOI: No ID Found -
American Journal of Therapeutics 2020
Topics: Dapsone; Facial Dermatoses; Humans; Rosacea
PubMed: 30946045
DOI: 10.1097/MJT.0000000000000903