scholarly journals Severe Adverse Drug Reactions to Quetiapine in Two Patients Carrying CYP2D6*4 Variants: A Case Report

2021 ◽  
Vol 22 (12) ◽  
pp. 6480
Author(s):  
Céline K. Stäuble ◽  
Markus L. Lampert ◽  
Thorsten Mikoteit ◽  
Martin Hatzinger ◽  
Kurt E. Hersberger ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Case Report ◽  
Adverse Drug Reactions ◽  
Active Metabolite ◽  
Hepatic Metabolism ◽  
Cytochrome P450 3A4 ◽  
Drug Reactions ◽  
Drug Induced ◽  
Potential Impact ◽  
Intermediate Metabolizer

We report two cases of patients who developed severe adverse drug reactions including persistent movement disorders, nausea, and vertigo during treatment with quetiapine at maximum daily doses ranging between 300 and 400 mg. The extensive hepatic metabolism of quetiapine is mainly attributed to cytochrome P450 3A4 (CYP3A4). However, there is recent evidence supporting the idea of CYP2D6 playing a role in the clearance of the quetiapine active metabolite norquetiapine. Interestingly, both patients we are reporting of are carriers of the CYP2D6*4 variant, predicting an intermediate metabolizer phenotype. Additionally, co-medication with a known CYP2D6 inhibitor and renal impairment might have further affected quetiapine pharmacokinetics. The herein reported cases could spark a discussion on the potential impact of a patient’s pharmacogenetic predisposition in the treatment with quetiapine. However, further studies are warranted to promote the adoption of pharmacogenetic testing for the prevention of drug-induced toxicities associated with quetiapine.

Nimodipine-induced junctional bradycardia in an elderly patient with subarachnoid hemorrhage

2020 ◽  
Vol 21 (6) ◽  
pp. 387-392
Author(s):  
Courtney L James ◽  
Marion T Turnbull ◽  
William D Freeman
Keyword(s):  
Elderly Patient ◽  
Cytochrome P450 ◽  
Case Report ◽  
Subarachnoid Hemorrhage ◽  
Adverse Events ◽  
Clinical Outcomes ◽  
Adverse Drug Reactions ◽  
Heart Block ◽  
Drug Reactions ◽  
Cytochrome P450 3A

Subarachnoid hemorrhage is a devastating form of stroke with often detrimental outcomes for patients. Here we describe a patient with subarachnoid hemorrhage treated with nimodipine, which resulted in marked bradycardia with junctional atrioventricular heart block. Nimodipine is metabolized predominantly by the cytochrome P450 3A subfamily, and its use is often associated with adverse events, such as hypotension and bradycardia, which can be exacerbated by advanced age. Our patient had the CYP3A5*3/*3 genotype, possibly predisposing her to poor metabolism of this drug. Our case report demonstrates the potential for pharmacogenomics in patients with subarachnoid hemorrhage to help predict their response to nimodipine, minimize adverse drug reactions, and potentially individualize dosing to improve future clinical outcomes.

scholarly journals Piperacillin/tazobactam induced toxic epidermal necrolysis and drug induced liver injury

2018 ◽  
Vol 5 (2) ◽  
pp. 460
Author(s):  
Hardeep S. Deep ◽  
Mohit Kumar ◽  
Barjinder Pal Singh ◽  
Nisha Kajla
Keyword(s):  
Drug Reaction ◽  
Case Report ◽  
Liver Injury ◽  
Toxic Epidermal Necrolysis ◽  
Adverse Drug Reactions ◽  
Drug Reactions ◽  
Drug Induced ◽  
Biochemical Characteristics ◽  
Drug Induced Liver Injury ◽  
Ultimate Outcome

The liver and skin are the organs most commonly involved in serious adverse drug reactions. Rarely a drug reaction can affect both organs concurrently. The association of drug induced liver injury (DILI) and toxic epidermal necrolysis (TEN) is even rarer and may be rarely reported. This is a case report on development of both TEN and DILI following use of piperacillin / tazobactam. We describe our experience of DILI occurring in association with TEN including the etiological agent responsible, its clinical/ biochemical characteristics and ultimate outcome.

Biology of Heme: Drug Interactions and Adverse Drug Reactions with CYP450

2019 ◽  
Vol 18 (23) ◽  
pp. 2042-2055 ◽  
Author(s):  
Neeraj Kumar ◽  
Heerak Chugh ◽  
Damini Sood ◽  
Snigdha Singh ◽  
Aarushi Singh ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Drug Metabolism ◽  
Drug Interactions ◽  
Adverse Drug Reactions ◽  
Genetic Defects ◽  
Drug Reactions ◽  
Detailed Structure ◽  
Synthesis And Degradation ◽  
Porphyrin Rings

Heme is central to functions of many biologically important enzymes (hemoproteins). It is an assembly of four porphyrin rings joined through methylene bridges with a central Fe (II). Heme is present in all cells, and its synthesis and degradation balance its amount in the cell. The deregulations of heme networks and incorporation in hemoproteins lead to pathogenic state. This article addresses the detailed structure, biosynthesis, degradation, and transportation associated afflictions to heme. The article is followed by its roles in various diseased conditions where it is produced mainly as the cause of increased hemolysis. It manifests the symptoms in diseases as it is a pro-oxidant, pro-inflammatory and pro-hemolytic agent. We have also discussed the genetic defects that tampered with the biosynthesis, degradation, and transportation of heme. In addition, a brief about the largest hemoprotein group of enzymes- Cytochrome P450 (CYP450) has been discussed with its roles in drug metabolism.

Importance of cytochrome P450 (CYP450) in adverse drug reactions due to drug–drug interactions: a PharmacoVigilance study in France

2012 ◽  
Vol 69 (4) ◽  
pp. 885-888 ◽  
Author(s):  
Anne Charlotte Danton ◽  
François Montastruc ◽  
Agnès Sommet ◽  
Geneviève Durrieu ◽  
Haleh Bagheri ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Drug Interactions ◽  
Adverse Drug Reactions ◽  
Drug Reactions

Cutaneous reactions to drugs

2020 ◽  
pp. 5752-5760
Author(s):  
Sarah Walsh ◽  
Daniel Creamer ◽  
Haur Yueh Lee
Keyword(s):  
Adverse Drug Reactions ◽  
Adverse Reactions ◽  
Normal Function ◽  
Stevens Johnson Syndrome ◽  
Drug Reactions ◽  
Drug Induced ◽  
Drug Eruptions ◽  
Fixed Drug ◽  
Iatrogenic Illness ◽  
Systemic Symptoms

Adverse reactions to medications are common and important cause of iatrogenic illness. Severe cutaneous adverse drug reactions include toxic epidermal necrolysis, Stevens–Johnson syndrome, drug reaction with eosinophilia and systemic symptoms, and acute generalized exanthematous pustulosis, which together constitute 2% of all adverse drug reactions and may be life-threatening. Less severe drug-induced skin reactions such as exanthems, urticaria, lichenoid drug rashes, and fixed drug eruptions are more common, sometimes termed benign cutaneous adverse reactions, and generally resolve without sequelae. Drugs may also cause adverse events due to alteration of the normal function of the skin or its appendages. This may take the form of photosensitivity, abnormal pigmentation, or disrupted growth of hair or nails.

scholarly journals Bibliometric analysis of adverse drug reactions and pharmacovigilance research activities in Nepal

2020 ◽  
Vol 11 ◽  
pp. 204209862092248
Author(s):  
Sunil Shrestha ◽  
Krisha Danekhu ◽  
Bhuvan KC ◽  
Subish Palaian ◽  
Mohamed Izham Mohamed Ibrahim
Keyword(s):  
Bibliometric Analysis ◽  
Adverse Drug Reactions ◽  
Case Reports ◽  
Research Performance ◽  
Case Series ◽  
Original Research ◽  
Drug Reactions ◽  
Drug Induced ◽  
Scientific Publications ◽  
Research Activities

Background: Bibliometric analyses have been used previously to study the measures of quality and impact of research performed in several health-related areas such as adverse drug reactions (ADRs) and pharmacovigilance (PV), etc. This method can assess the research performance of publications quantitatively and statistically. There is no evidence of bibilometric studies analyzing ADRs and PV from Nepal. Therefore, the present study aimed to assess scientific output on ADRs and PV-related research activities in Nepal using a bibliometric analysis of publications from 2004 January to December 2018, that is, 15 years. Methods: A systematic search was conducted in PubMed, Web of Science, Google Scholar, Scopus and Nepal Journal Online (NepJOL) databases. ‘Adverse Drug Reactions‘ or ‘ADRs‘ or ‘ADR‘ or ‘Adverse drug reaction‘ or ‘AE‘ or ‘Adverse Event‘ or ‘Drug-Induced Reaction‘ or ‘Pharmacovigilance‘ or ‘PV‘ and ‘Nepal‘. The search covered 15 years (January 2004 to December 2018) of study on ADRs and PV in Nepal. Only articles retrieved from databases were included, whereas published/unpublished drug bulletins, pharmacy newsletters and thesis were excluded. The articles thus retrieved were recorded, and thereafter analyzed. Word count code was used for the analysis of keywords used in the retrieved articles. Results: A total of 124 articles were retrieved, with the highest rate of publications in 2006 and 2007, with 16 papers each. Among the articles, 10 (8.1%) were published in Kathmandu University Medical Journal (KUMJ). Single papers were published in 38 different journals. Brief reports (1.6%), case reports (31.2%), case series (0.8%), education forums (0.8%), letters to the editor (5.6%), original research articles (41.9%), review articles (9.7%), short communications and short reports (8.1%) on ADRs and PV were recorded. Out of 124 papers, 52 (41.9%) were original research publications. The majority (74.1%) of research was done in the category of ADR incidence, types, prevention, and management, followed by policy and suggestions for strengthening national and regional pharmacovigilance centers of Nepal (14.5%). Conclusions: During the study years, there was an increase in scientific publications on drug safety. A total of 124 published articles were found during bibliometric analysis of ADRs and PV research activities in Nepal.

scholarly journals HLA Association with Drug-Induced Adverse Reactions

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Wen-Lang Fan ◽  
Meng-Shin Shiao ◽  
Rosaline Chung-Yee Hui ◽  
Shih-Chi Su ◽  
Chuang-Wei Wang ◽  
...  
Keyword(s):  
Adverse Drug Reactions ◽  
Antithyroid Drug ◽  
Human Leukocyte ◽  
Stevens Johnson Syndrome ◽  
Drug Reactions ◽  
Drug Induced ◽  
Hla Association ◽  
Hla Genes ◽  
Johnson Syndrome ◽  
Life Threatening

Adverse drug reactions (ADRs) remain a common and major problem in healthcare. Severe cutaneous adverse drug reactions (SCARs), such as Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) with mortality rate ranges from 10% to more than 30%, can be life threatening. A number of recent studies demonstrated that ADRs possess strong genetic predisposition. ADRs induced by several drugs have been shown to have significant associations with specific alleles of human leukocyte antigen (HLA) genes. For example, hypersensitivity to abacavir, a drug used for treating of human immunodeficiency virus (HIV) infection, has been proposed to be associated with allele 57:01 of HLA-B gene (terms HLA-B∗57:01). The incidences of abacavir hypersensitivity are much higher in Caucasians compared to other populations due to various allele frequencies in different ethnic populations. The antithyroid drug- (ATDs- ) induced agranulocytosis are strongly associated with two alleles: HLA-B∗38:02 and HLA-DRB1∗08:03. In addition, HLA-B∗15:02 allele was reported to be related to carbamazepine-induced SJS/TEN, and HLA-B∗57:01 in abacavir hypersensitivity and flucloxacillin induced drug-induced liver injury (DILI). In this review, we summarized the alleles of HLA genes which have been proposed to have association with ADRs caused by different drugs.

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