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

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.

Download Full-text

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

International Journal of Molecular Sciences ◽

10.3390/ijms22126480 ◽

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.

Download Full-text

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

Current Topics in Medicinal Chemistry ◽

10.2174/1568026619666181129124638 ◽

2019 ◽

Vol 18 (23) ◽

pp. 2042-2055 ◽

Cited By ~ 4

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.

Download Full-text

Improving reporting of adverse events and adverse drug reactions following injections of Chinese materia medica

Journal of Evidence-Based Medicine ◽

10.1111/j.1756-5391.2010.01055.x ◽

2010 ◽

Vol 3 (1) ◽

pp. 5-10 ◽

Cited By ~ 12

Author(s):

Zhao-Xiang Bian ◽

Hao-Yao Tian ◽

Lin Gao ◽

Hong-Cai Shang ◽

Tai-Xiang Wu ◽

...

Keyword(s):

Adverse Events ◽

Adverse Drug Reactions ◽

Drug Reactions ◽

Chinese Materia Medica ◽

Materia Medica

Download Full-text

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

European Journal of Clinical Pharmacology ◽

10.1007/s00228-012-1394-3 ◽

2012 ◽

Vol 69 (4) ◽

pp. 885-888 ◽

Cited By ~ 17

Author(s):

Anne Charlotte Danton ◽

François Montastruc ◽

Agnès Sommet ◽

Geneviève Durrieu ◽

Haleh Bagheri ◽

...

Keyword(s):

Cytochrome P450 ◽

Drug Interactions ◽

Adverse Drug Reactions ◽

Drug Reactions

Download Full-text

Major Aspects of Detection and Monitoring of Adverse Reactions Associated with Cephalosporin Antibiotic Treatment

Safety and Risk of Pharmacotherapy ◽

10.30895/2312-7821-2021-9-1-34-42 ◽

2021 ◽

Vol 9 (1) ◽

pp. 34-42

Author(s):

E. Yu. Demchenkova ◽

G. I. Gorodetskaya ◽

I. A. Mazerkina ◽

M. V. Zhuravleva ◽

A. S. Kazakov ◽

...

Keyword(s):

Adverse Events ◽

Adverse Drug Reactions ◽

Patient Information ◽

Adverse Reactions ◽

Stevens Johnson Syndrome ◽

Drug Reactions ◽

Patient Information Leaflets ◽

Information Leaflets ◽

Spontaneous Reports ◽

Cephalosporin Antibiotics

Widespread use of cephalosporin antibiotics in clinical practice calls for greater attention to the risk of adverse drug reactions. Information on serious or unexpected adverse events reported during post-marketing experience is submitted to national and international pharmacovigilance databases. Analysis of these reports helps to identify new adverse drug reactions.The aim of the study was to analyse the safety profile of cephalosporin antibiotics based on spontaneous reports in the international VigiBase database.Materials and methods: the analysis of the adverse reaction profile of cephalosporin antibiotics was based on MedDRA system organ classes and included spontaneous reports submitted to VigiBase from the moment of its creation until August 2020.Results: the authors identified the most clinically significant adverse reactions for different cephalosporin generations. They compared and analysed information on adverse events in VigiBase and in patient information leaflets of medicinal products authorised in the Russian Federation. It was demonstrated that some serious events described in VigiBase spontaneous reports for V-generation cephalosporins are not included in the “Side effects” section of the patient information leaflets. According to VigiBase, the use of ceftaroline was associated with the development of generalised exfoliative dermatitis, Stevens–Johnson syndrome, tubulointerstitial nephritis, while the use of ceftolozane was associated with acute kidney injury, renal insufficiency, sepsis, pneumonia, and respiratory insufficiency.Conclusion: reporting of unexpected and serious adverse drug reactions to cephalosporin antibiotics is an important task of healthcare practitioners. Availability of information on class-specific and generation-specific serious adverse reactions will help predict and prevent their development.

Download Full-text

NEUROPSYCHIATRIC ADVERSE EFFECTS OF ANTIBACTERIAL AGENTS

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2021v13i12.42482 ◽

2021 ◽

pp. 1-8

Author(s):

SANTA TREASA CYRIAC ◽

DIVYA SARA IYPE

Keyword(s):

Adverse Effects ◽

Adverse Events ◽

Adverse Drug Reactions ◽

Bacterial Growth ◽

Antibacterial Agents ◽

Acute Psychosis ◽

Drug Reactions ◽

Medical Practitioners ◽

General Management ◽

Neuropsychiatric Adverse Effects

Anti-bacterial are agents that inhibit bacterial growth or kills bacteria and are a sub-type of antimicrobials. These are drugs used to treat infections, but they sometimes pose a threat of adverse events. Some of these adverse events are neuropsychiatric, which are generally hard to diagnose and is often paid less attention. They account for about 30% of total Adverse drug reactions (ADRs) caused by drugs in patients without mental abnormalities. The spectrum ranges from episodes of seizure to acute psychosis. The article emphasizes the frequency of such adverse events and means to raise awareness among medical practitioners regarding the same. The various neuropsychiatric adverse effects and the agents responsible have been reviewed, along with their possible mechanisms and general management. The information for writing this review was selected by searching for keywords such as Neurotoxicity, GABA, Psychosis, Naranjo scale, and Antibiomania in databases such as Google Scholar, PubMed, Elsevier, etc. After searching the articles in the above-mentioned databases, the articles were screened concerning their importance with our work and according to their title and abstract. Additional articles were discovered by checking the references in the current study's citations. Using this method, the various neuropsychiatric adverse effects of Antibacterial agents were summarized in this review.

Download Full-text

Adverse Drug Reactions (ADR) and Adverse Events (AE)

The SAGE Encyclopedia of Pharmacology and Society ◽

10.4135/9781483349985.n22 ◽

2016 ◽

Keyword(s):

Adverse Events ◽

Adverse Drug Reactions ◽

Drug Reactions

Download Full-text

Adverse Events Associated with Nifurtimox Treatment for Chagas Disease in Children and Adults

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01135-20 ◽

2020 ◽

Author(s):

A. J. Berenstein ◽

N. Falk ◽

G. Moscatelli ◽

S. Moroni ◽

N. González ◽

...

Keyword(s):

Retrospective Study ◽

Adverse Events ◽

Chagas Disease ◽

Adverse Drug Reactions ◽

Drug Tolerance ◽

Drug Reactions ◽

Safety Concerns ◽

Scarce Data

BACKGROUND: Nifurtimox (NF) is one of the only two drugs currently available for Chagas disease (ChD) treatment. However, there is scarce data on NF safety, and many physicians defer or refuse NF treatment because of concerns about drug tolerance. METHODS: Retrospective study of adverse drug reactions (ADRs) associated with NF treatment of ChD. Children received NF doses of 10-15 mg/kg/day for 60-90 days, and adults 8-10 mg/kg/day for 30 days. Results: 215 children (median age: 2.6yrs, range 0-17) and 105 adults (median age: 34yrs, range 18-57) were enrolled. Overall, 127/320 (39.7%) patients developed ADRs, with an incidence of 64/105 in adults, and 63/215 in children (OR = 3.7, 95%CI [2.2;6.3]). We observed 215 ADRs, 131 in adults (median: 2 events/patient (IQR25-75= 1-3) and 84 in children (median: 1 event/patient (IQR25-75= 1-1.5) (PAdjusted < 0.001). ADRs were mainly mild and moderate. Severe ADRs were infrequent (1.2% in children and 0.9% in adults). Nutritional, central nervous and digestive systems were the most frequently affected, without differences between both groups. Treatment was discontinued in 31/320 (9.7%) patients without differences between groups. However, ADR-related discontinuations occurred more frequently in adults than in children (OR = 5.5, 95%CI = [1.5;24]). CONCLUSIONS: Our study supports the safety of NF for ChD treatment. Delaying NF treatment due to safety concerns does not seem to be supported by the evidence.

Download Full-text