Preservation of basophils in dapsone‐induced agranulocytosis suggests a possible pathogenetic role for leucocyte peroxidases

Besser, Martin; Vera, Jaime H.; Clark, John A.; Chitnavis, Dipti; Beatty, Chester; Vassiliou, George S.

doi:10.1111/j.1751-553x.2007.00983.x

Cited by 12 publications

(4 citation statements)

References 7 publications

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“…It is usually asymptomatic, and the first indication is an infection heralded by symptoms such as a sore throat and/or fever. Although agranulocytosis implies that there is an absence of all granulocytes, basophils can be spared (Besser et al, 2009), and lymphopenia can be present (Tesfa et al, 2009). This may be a reflection of the mechanism because basophils do not have the same peroxidase activity as neutrophils and eosinophils, whereas lymphopenia could be the result of an immune response.…”

Section: Hematologic Adverse Reactionsmentioning

confidence: 99%

Idiosyncratic Adverse Drug Reactions: Current Concepts

2013

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Section: Hematologic Adverse Reactionsmentioning

confidence: 99%

Idiosyncratic Adverse Drug Reactions: Current Concepts

2013

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“…Even in patients who genetically had low myeloperoxidase activity, the tendency to develop clozapine-induced agranulocytosis was not reduced (Mosyagin et al, 2004). Nonetheless, the involvement of myeloperoxidase in these processes is supported by the fact that basophilic granulocytes, which have no peroxidase activity, remain unaffected in agranulocytosis (Besser et al, 2009). This is further supported by the fact that in the bone marrow of agranulocytosis patients, a deficiency of myeloid progenitor cells down to the promyelocyte stage is typically observed.…”

Section: Why Are Neutrophils Affected By Idiosyncratic Drug Effects?mentioning

confidence: 96%

Drug-Induced Idiosyncratic Agranulocytosis - Infrequent but Dangerous

Rattay

Benndorf

2021

Front. Pharmacol.

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Drug-induced agranulocytosis is a life-threatening side effect that usually manifests as a severe form of neutropenia associated with fever or signs of sepsis. It can occur as a problem in the context of therapy with a wide variety of drug classes. Numerous drugs are capable of triggering the rare idiosyncratic form of agranulocytosis, which, unlike agranulocytosis induced by cytotoxic drugs in cancer chemotherapy, is characterised by “bizzare” type B or hypersensitivity reactions, poor predictability and a mainly low incidence. The idiosyncratic reactions are thought to be initiated by chemically reactive drugs or reactive metabolites that react with proteins and may subsequently elicit an immune response, particularly directed against neutrophils and their precursors. Cells or organs that exhibit specific metabolic and biotransformation activity are therefore frequently affected. In this review, we provide an update on the understanding of drug-induced idiosyncratic agranulocytosis. Using important triggering drugs as examples, we will summarise and discuss the chemical, the biotransformation-related, the mechanistic and the therapeutic basis of this clinically relevant and undesirable side effect.

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“…40 Dapsone is metabolized by peroxidases to nitroso derivatives in non-hemopoietic cells. 41 The drug is metabolized to the hydroxylamine metabolite by CYP2C9, 42 or by more than one CYP450 enzyme. 43 Various reports deal with toxicity.…”

Section: Dapsonementioning

confidence: 99%

Novel, unifying mechanism for aromatic primary-amines (therapeutics, carcinogens and toxins): electron transfer, reactive oxygen species, oxidative stress and metabolites

Kovacic

Somanathan

2011

Med. Chem. Commun.

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Aromatic primary-amines (APAs) display physiological activity in various areas, including therapeutics, carcinogens and toxicants. More familiar examples include aniline and derivatives, naphthylamines, dapsone, sulfa drugs and procaineamide. Diverse mechanisms have been proposed for these agents. However, there has not been recognition for a unifying theme entailing electron transfer (ET), reactive oxygen species (ROS) and oxidative stress (OS). Prior reviews demonstrate that the ET-ROS-OS theme can be applied to therapeutics, carcinogens and toxicants. The preponderance of bioactive substances or their metabolites incorporate ET functionalities, which, we believe, play an important role in physiological responses. Among these, the focus in the present review is on APAs which generate ET hydroxylamine and nitroso metabolites which can generate ROS via redox cycling. Evidence suggests involvement of the metabolites in the bioactivity. Further support is provided by AO protection of toxicity which supports involvement of ROS. Apparently, a multifaceted approach best pertains.

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Preservation of basophils in dapsone‐induced agranulocytosis suggests a possible pathogenetic role for leucocyte peroxidases

Cited by 12 publications

References 7 publications

Idiosyncratic Adverse Drug Reactions: Current Concepts

Idiosyncratic Adverse Drug Reactions: Current Concepts

Drug-Induced Idiosyncratic Agranulocytosis - Infrequent but Dangerous

Novel, unifying mechanism for aromatic primary-amines (therapeutics, carcinogens and toxins): electron transfer, reactive oxygen species, oxidative stress and metabolites

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