scholarly journals Drug-Induced Idiosyncratic Agranulocytosis - Infrequent but Dangerous

2021 ◽  
Vol 12 ◽  
Author(s):  
Bernd Rattay ◽  
Ralf A. Benndorf
Keyword(s):  
Side Effect ◽  
Severe Form ◽  
Reactive Metabolites ◽  
Hypersensitivity Reactions ◽  
Undesirable Side Effect ◽  
Type B ◽  
Drug Induced ◽  
Drug Classes ◽  
Life Threatening ◽  
Low Incidence

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.

scholarly journals Increased Incidence of Invasive Haemophilus influenzae Disease Driven by Non-Type B Isolates in Ontario, Canada, 2014 to 2018

2021 ◽  
Author(s):  
Lisa R. McTaggart ◽  
Kirby Cronin ◽  
Chi Yon Seo ◽  
Sarah Wilson ◽  
Samir N. Patel ◽  
...  
Keyword(s):  
Haemophilus Influenzae ◽  
World Health ◽  
Type B ◽  
Content Type ◽  
Vaccination Programs ◽  
The World ◽  
Life Threatening ◽  
Low Incidence ◽  
Serotype B ◽  
Health Organization

H. influenzae can cause serious invasive, life-threatening disease and is considered 1 of 12 priority pathogens by the World Health Organization. Widespread vaccination against H. influenzae serotype b (Hib) has resulted in very low incidence of Hib in Ontario and other regions that have vaccination programs.

scholarly journals Case Report about Fatal or Near-Fatal Hypersensitivity Reactions to Cetuximab: Anticetuximab IgE as a Valuable Screening Test

2014 ◽  
Vol 8 ◽  
pp. CMO.S13897 ◽  
Author(s):  
Benoît Dupont ◽  
Delphine Mariotte ◽  
Cristian Moldovan ◽  
Jean-Michel Grellard ◽  
Marie-Claude Vergnaud ◽  
...  
Keyword(s):  
At Risk ◽  
Case Report ◽  
Side Effect ◽  
Screening Test ◽  
Hypersensitivity Reactions ◽  
Life Threatening

Hypersensitivity reactions are a classic side effect of cetuximab. We report the cases of three patients who developed life-threatening hypersensitivity to cetuximab, which could have been predicted by assessing the concentration of serum anticetuximab immunoglobulin (Ig)E. The anti-cetuximab IgE concentration could be an interesting test to predict which patients are at risk of experiencing severe hypersensitivity reactions to cetuximab.

Emergency endovascular stent-grafting for life-threatening acute type B aortic dissections

2004 ◽  
Vol 52 (S 1) ◽  
Author(s):  
LF Duebener ◽  
V Geist ◽  
G Richardt ◽  
A N�tzold ◽  
M Misfeld ◽  
...  
Keyword(s):  
Acute Type ◽  
Endovascular Stent ◽  
Type B ◽  
Stent Grafting ◽  
Endovascular Stent Grafting ◽  
Life Threatening ◽  
Aortic Dissections

Nonacog Alpha - an Efficient Therapeutic Option in Hemostase Management for Hemophilia Type B in Patients with Elective Arthropalsties

2018 ◽  
Vol 69 (7) ◽  
pp. 1911-1914
Author(s):  
Oana Viola Badulescu ◽  
Razvan Tudor ◽  
Wilhelm Friedl ◽  
Manuela Ciocoiu ◽  
Paul Dan Sirbu
Keyword(s):  
Therapeutic Option ◽  
Coagulation Factors ◽  
Factor Ix ◽  
Joint Disease ◽  
Type B ◽  
Total Endoprosthesis ◽  
Recombinant Factor Ix ◽  
Bleeding Episodes ◽  
Low Incidence ◽  
Articular Pathology

Hemophilia is a hereditary coagulopathy that is largely in the attention of developing countries, not because of its low incidence, but because of the high costs involved in the treatment of the disease and its disabling consequences of the disease, if treated inappropriately. The concentrates of coagulation factors currently available for the substitution treatment of hemophilic patients have undergone additional viral purification and inactivation techniques, in order to achieve a higher infectious safety, an aspect that also implies an increase in treatment costs for these patients. Currently, the major morbidity of patients with hemophilia is represented by the disabling articular pathology, secondary to repetitive bleeding episodes developed in the articular space. Although it has been proved that the prophylactic administration of coagulation factors helps to prevent joint disease in the case of patients that were not subject to prophylaxis, the repeated bleeding in the joints induces synovitis, which is irreversible and may progress despite subsequent prophylaxis. Under these conditions, total joint arthroplasty remains the only solution to reduce both, pain and subsequent bleeding episodes of hemophilic arthropathy. Effective hemostasis is a basic condition for successful interventions in hemophilic patients. In this regard, this paper aims to highlight the effectiveness of Nonacog Alpha, a product that contains recombinant factor IX, in the management of hemostasis, in the case of a patient with type B hemophilia, with indication of total endoprosthesis of the left hip.

Gauging Reactive Metabolites in Drug-Induced Toxicity

2014 ◽  
Vol 22 (4) ◽  
pp. 465-489 ◽  
Author(s):  
Marsha Eno ◽  
Michael Cameron
Keyword(s):  
Reactive Metabolites ◽  
Drug Induced

The Chemistry of Drugs to Treat Candida albicans

2019 ◽  
Vol 19 (28) ◽  
pp. 2554-2566 ◽  
Author(s):  
Aurelio Ortiz ◽  
Estibaliz Sansinenea
Keyword(s):  
Candida Species ◽  
Antifungal Drugs ◽  
New Drugs ◽  
Drug Classes ◽  
Life Threatening ◽  
Antifungal Substances ◽  
High Level ◽  
Systemic Infections ◽  
New Compounds ◽  
Level Resistance

Background:: Candida species are in various parts of the human body as commensals. However, they can cause local mucosal infections and, sometimes, systemic infections in which Candida species can spread to all major organs and colonize them. Objective:: For the effective treatment of the mucosal infections and systemic life-threatening fungal diseases, a considerably large number of antifungal drugs have been developed and used for clinical purposes that comprise agents from four main drug classes: the polyenes, azoles, echinocandins, and antimetabolites. Method: : The synthesis of some of these drugs is available, allowing synthetic modification of the molecules to improve the biological activity against Candida species. The synthetic methodology for each compound is reviewed. Results: : The use of these compounds has caused a high-level resistance against these drugs, and therefore, new antifungal substances have been described in the last years. The organic synthesis of the known and new compounds is reported. Conclusion: : This article summarizes the chemistry of the existing agents, both the old drugs and new drugs, in the treatment of infections due to C. albicans, including the synthesis of the existing drugs.

scholarly journals Drug Induced Encephalopathy in Patients with Chronic Kidney Disease: A Case Series

2018 ◽  
Vol 8 (2) ◽  
pp. 172-176
Author(s):  
Wasim Md Mohosin Ul Haque ◽  
Tabassum Samad ◽  
Muhammad Abdur Rahim ◽  
Shudhanshu Kumar Saha ◽  
Sarwar Iqbal
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Impairment ◽  
Side Effect ◽  
Case Series ◽  
Special Group ◽  
Drug Induced ◽  
Reduced Dose

Drug induced encephalopathy is an established side effect of many drugs when used in a higher dose. Though we do not encounter this side effect frequently in our day to day practice, yet with renal impairment this is not uncommon. Even with a reduced dose many of these can precipitate encephalopathy in this special group of patients. We are presenting here a series of seven such cases of drug induced encephalopathy in patients with renal impairment.Birdem Med J 2018; 8(2): 172-176

scholarly journals Investigating the Mechanism of Trimethoprim-Induced Skin Rash and Liver Injury

2021 ◽  
Author(s):  
Yanshan Cao ◽  
Ahsan Bairam ◽  
Alison Jee ◽  
Ming Liu ◽  
Jack Uetrecht
Keyword(s):  
Liver Injury ◽  
Skin Rash ◽  
Covalent Binding ◽  
Reactive Metabolites ◽  
Important Data ◽  
Drug Induced ◽  
Interindividual Differences ◽  
Immune Mediated ◽  
Sulfate Conjugate

Abstract Trimethoprim (TMP)-induced skin rash and liver injury are likely to involve the formation of reactive metabolites. Analogous to nevirapine-induced skin rash, one possible reactive metabolite is the sulfate conjugate of α-hydroxyTMP, a metabolite of TMP. We synthesized this sulfate and found that it reacts with proteins in vitro. We produced a TMP-antiserum and found covalent binding of TMP in the liver of TMP-treated rats. However, we found that α-hydroxyTMP is not a substrate for human sulfotransferases, and we did not detect covalent binding in the skin of TMP-treated rats. Although less reactive than the sulfate, α-hydroxyTMP was found to covalently bind to liver and skin proteins in vitro. Even though there was covalent binding to liver proteins, TMP did not cause liver injury in rats or in our impaired immune tolerance mouse model that has been able to unmask the ability of other drugs to cause immune-mediated liver injury. This is likely because there was much less covalent binding of TMP in the livers of TMP-treated mice than TMP-treated rats. It is possible that some patients have a sulfotransferase that can produce the reactive benzylic sulfate; however, α-hydroxyTMP, itself, has sufficient reactivity to covalently bind to proteins in the skin and may be responsible for TMP-induced skin rash. Interspecies and interindividual differences in TMP metabolism may be one factor that determines the risk of TMP-induced skin rash. This study provides important data required to understand the mechanism of TMP-induced skin rash and drug-induced skin rash in general.

scholarly journals Pustular Rash in Crohn’s Patient on Ustekinumab Raises Concern for Drug-Induced Paradoxical Psoriasis

2021 ◽  
pp. 662-666
Author(s):  
Mitra Barahimi ◽  
Scott Lee ◽  
Kindra Clark-Snustad
Keyword(s):  
Side Effect ◽  
De Novo ◽  
Pustular Psoriasis ◽  
Initial Weight ◽  
Drug Induced ◽  
Clinical Recurrence ◽  
Potential Side Effect ◽  
First Case ◽  
Tnf Antagonist ◽  
Subcorneal Pustular Dermatosis

We report the case of a 51-year-old male with Crohn’s disease (CD) who developed a reproducible pustular rash after ustekinumab (UST) administration. The patient first presented with a pustular rash on his hands, body, extremities, and scalp starting 5 weeks after his initial weight-based UST induction. The rash resolved spontaneously, then recurred 4 weeks after his first subcutaneous maintenance dose of UST 90 mg. Biopsy of the affected area demonstrated subcorneal pustular dermatosis (SPD). UST was discontinued and the rash resolved. Unfortunately, the patient experienced clinical recurrence of CD, and given prior failure of multiple CD medications, UST was restarted with premedication. Two weeks after UST re-induction, the rash recurred, though less severe. Given improvement in CD symptoms, UST was continued and the rash managed with topical corticosteroids. This is the first case of drug-induced SPD associated with UST. One case report has previously described de novo pustular psoriasis associated with UST in a patient with CD and enteropathic arthritis. Notably, SPD and pustular psoriasis can be histologically indistinguishable. The development of a paradoxical psoriasiform rash is thought to be one of the few dose and duration dependent side effects of TNF-antagonist therapy but has not previously been established as a side effect of UST. This case demonstrates a new potential side effect of UST.

scholarly journals Application of ultrasound-guided intranodal lymphangiography and embolisation in cancer patients with postoperative lymphatic leakage

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xingwei Sun ◽  
Feng Zhou ◽  
Xuming Bai ◽  
Qiang Yuan ◽  
Mingqing Zhang ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Operative Time ◽  
Length Of Hospital Stay ◽  
Chylous Ascites ◽  
Pelvic Surgery ◽  
Ultrasound Guided ◽  
Technical Success Rate ◽  
Life Threatening ◽  
Low Incidence ◽  
Intranodal Lymphangiography

Abstract Background Traumatic lymphatic leakage is a rare but potentially life-threatening complication. The purpose of this study was to introduce ultrasound-guided intranodal lymphangiography and embolisation techniques for postoperative lymphatic leakage in patients with cancer. Methods From January 2018 through June 2020, seven cancer patients (three males, four females, aged 59–75 years [mean 67.57 ± 6.11 years]) developed lymphatic leakage after abdominal or pelvic surgery, with drainage volumes ranging from 550 to 1200 mL per day. The procedure and follow-up of ultrasound-guided intranodal lymphangiography and embolisation were recorded. This study retrospectively analysed the technical success rate, operative time, length of hospital stay, clinical efficacy, and complications. Results The operation was technically successful in all patients. Angiography revealed leakage, and embolisation was performed in all seven patients (7/7, 100%). The operative time of angiography and embolisation was 41 to 68 min, with an average time of 53.29 ± 10.27 min. The mean length of stay was 3.51 ± 1.13 days. Lymph node embolisation was clinically successful in five patients (5/7, 71.43%), who had a significant reduction in or disappearance of chylous ascites. The other two patients received surgical treatment 2 weeks later due to poor results after embolisation. All patients were followed for 2 weeks. No serious complications or only minor complications were found in all the patients. Conclusions Ultrasound-guided intranodal lymphangiography and embolisation were well tolerated by the patients, who experienced a low incidence of complications. Early intervention is recommended for cancer patients with postoperative lymphatic leakage.

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