scholarly journals Metabolic Profiles of Propofol and Fospropofol: Clinical and Forensic Interpretative Aspects

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Ricardo Jorge Dinis-Oliveira
Keyword(s):  
Health Professionals ◽  
Metabolic Pathways ◽  
Adverse Reactions ◽  
Interindividual Variability ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Myocardial Failure ◽  
Cardiac Depression ◽  
Accidental Overdose ◽  
Cytochrome P450 Isoforms ◽  
Polymorphic Enzymes

Propofol is an intravenous short-acting anesthetic widely used to induce and maintain general anesthesia and to provide procedural sedation. The potential for propofol dependency and abuse has been recognized, and several cases of accidental overdose and suicide have emerged, mostly among the health professionals. Different studies have demonstrated an unpredictable interindividual variability of propofol pharmacokinetics and pharmacodynamics with forensic and clinical adverse relevant outcomes (e.g., pronounced respiratory and cardiac depression), namely, due to polymorphisms in the UDP-glucuronosyltransferase and cytochrome P450 isoforms and drugs administered concurrently. In this work the pharmacokinetics of propofol and fospropofol with particular focus on metabolic pathways is fully reviewed. It is concluded that knowing the metabolism of propofol may lead to the development of new clues to help further toxicological and clinical interpretations and to reduce serious adverse reactions such as respiratory failure, metabolic acidosis, rhabdomyolysis, cardiac bradyarrhythmias, hypotension and myocardial failure, anaphylaxis, hypertriglyceridemia, renal failure, hepatomegaly, hepatic steatosis, acute pancreatitis, abuse, and death. Particularly, further studies aiming to characterize polymorphic enzymes involved in the metabolic pathway, the development of additional routine forensic toxicological analysis, and the relatively new field of ‘‘omics’’ technology, namely, metabolomics, can offer more in explaining the unpredictable interindividual variability.

scholarly journals How polymorphisms of the cytochrome P450 genes affect ibuprofen and diclofenac metabolism and toxicity / Kako polimorfizmi gena citokroma P450 utječu na metabolizam i toksičnost ibuprofena i diklofenaka

2016 ◽  
Vol 67 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Valon Krasniqi ◽  
Aleksandar Dimovski ◽  
Iva Klarica Domjanović ◽  
Ivan Bilić ◽  
Nada Božina
Keyword(s):  
Cytochrome P450 ◽  
Clinical Practice ◽  
Drug Metabolism ◽  
Metabolic Pathways ◽  
Adverse Reactions ◽  
Interindividual Variability ◽  
Drug Reactions ◽  
Increased Risk ◽  
Cytochrome P450 Genes ◽  
Drug Efficiency

Abstract Interindividual variability in drug metabolism is an important cause of adverse drug reactions and variability in drug efficiency. Polymorphisms of cytochrome P450 (CYPs) genes have a significant effect on drug metabolism and toxicity. This review brings an update about how genetic polymorphisms of CYP2C8 and CYP2C9 enzymes affect the disposition and clinical outcomes of ibuprofen and diclofenac, two of the most common pain relievers. The most common side effects associated with the influence of CYP2C8*3 and CYP2C9*2*3 variants on ibuprofen and diclofenac pharmacokinetics are hepatotoxicity and gastrointestinal bleeding. CYP genotyping may therefore identify patients at increased risk of these adverse reactions, and these patients could have their doses adjusted or start receiving another NSAID that does not share the same metabolic pathways with ibuprofen or diclofenac. However, before genotyping is introduced into regular clinical practice, more research is needed to evaluate the effectiveness of this strategy in improving treatment with ibuprofen and diclofenac.

scholarly journals Age-Related Changes in the Hepatic Pharmacology and Toxicology of Paracetamol

2011 ◽  
Vol 2011 ◽  
pp. 1-14 ◽  
Author(s):  
Sarah J. Mitchell ◽  
Alice E. Kane ◽  
Sarah N. Hilmer
Keyword(s):  
Older Adults ◽  
Hepatic Clearance ◽  
Optimal Dose ◽  
Interindividual Variation ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Dose Selection ◽  
Age Related ◽  
Accidental Overdose ◽  
Toxicity Of Drugs ◽  
Age Related Changes

Optimal pharmacotherapy is determined when the pharmacokinetics and pharmacodynamics of the drug are understood. However, the age-related changes in pharmacokinetics and pharmacodynamics, as well as the increased interindividual variation mean optimal dose selection are a challenge for prescribing in older adults. Poor understanding of how hepatic clearance and toxicity are different with age results in suboptimal dose selection, poor efficacy, and/or increased toxicity. Of particular concern is the analgesic paracetamol which has been in use for more than 50 years and is consumed by a large proportion of older adults. Paracetamol is considered to be a relatively safe drug; however, caution must be taken because of its potential for toxicity. Paracetamol-induced liver injury from accidental overdose accounts for up to 55% of cases in older adults. Better understanding of how age affects the hepatic clearance and toxicity of drugs will contribute to evidence-based prescribing for older people, leading to fewer adverse drug reactions without loss of benefit.

Explaining Interindividual Variability of Docetaxel Pharmacokinetics and Pharmacodynamics in Asians Through Phenotyping and Genotyping Strategies

2002 ◽  
Vol 20 (17) ◽  
pp. 3683-3690 ◽  
Author(s):  
Boon-Cher Goh ◽  
Soo-Chin Lee ◽  
Ling-Zhi Wang ◽  
Lu Fan ◽  
Jia-Yi Guo ◽  
...  
Keyword(s):  
Interindividual Variability ◽  
Performance Status ◽  
Regulatory Region ◽  
Area Under The Curve ◽  
Serum Levels ◽  
Pharmacokinetic Data ◽  
Data Sets ◽  
Pharmacokinetics And Pharmacodynamics ◽  
C3435t Polymorphism ◽  
And Performance

PURPOSE: To explain the variability of docetaxel pharmacokinetics through study of CYP3A phenotype and genotype, and MDR1 genotype. PATIENTS AND METHODS: We studied the pharmacokinetics and pharmacodynamics of docetaxel in patients in whom it was indicated and who had not received known CYP3A4 substrates. Midazolam was administered intravenously to these patients at least 2 days before docetaxel treatment, and systemic clearances of both drugs were correlated. Patients were characterized for polymorphisms in the CYP3A4 promoter region, CYP3A5, and the C3435T polymorphism of MDR1. RESULTS: Thirty-two patients were enrolled, of whom 31 had full pharmacokinetic data sets. Docetaxel clearance correlated with midazolam clearance, body-surface area, serum albumin, and performance status. Docetaxel and midazolam clearances were normally distributed. In multiple linear regression analyses, midazolam clearance and performance status were the only significant covariates of docetaxel clearance, and the area under the curve of docetaxel, serum levels of alpha-1-acid glycoprotein, and ALT were significant predictors of nadir neutrophil count. No polymorphisms were detected in the 5′ regulatory region of CYP3A4. Nine patients of 25 studied were homozygous for the CYP3A5*3 genotype, and had lower mean clearance of midazolam but not docetaxel. The T/T genotype at the C3435T of MDR1, which is associated with reduced P-glycoprotein function, was found in eight of 27 patients. CONCLUSION: Midazolam may be used as a probe drug for CYP3A activity to predict docetaxel clearances, hence reducing interindividual variability. Homozygotes for CYP3A5*3 and C3435T of MDR1 are common in our population, and their effects on pharmacokinetics of relevant substrates should be studied further.

scholarly journals Adverse Oral Reactions Associated with Low Doses of Methotrexate

2020 ◽  
Vol 8 (4) ◽  
pp. 205-210
Author(s):  
N. V. Izmozherova ◽  
A. A. Popov ◽  
E. F. Gaysina ◽  
M. N. Dobrinskaya ◽  
V. M. Bakhtin ◽  
...  
Keyword(s):  
Adverse Reactions ◽  
Drug Withdrawal ◽  
Symptomatic Therapy ◽  
Oral Lesions ◽  
Low Doses ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Medical Specialties ◽  
Potential Development ◽  
Lichenoid Reactions ◽  
Drug Pharmacokinetics

Doctors of various medical specialties often encounter adverse drug reactions in their clinical practice. Methotrexate (MTX) can cause adverse reactions in the oral cavity, primarily erosions and ulcerations. The aim of the study was to analyse scientific literature on the prevalence, pathophysiological mechanisms, risk factors for oral lesions associated with low doses of MTX, their prevention and treatment. It was demonstrated that the most frequent oral adverse reactions associated with low doses of MTX are hard-to-heal painful necrotic and often irregularly shaped lesions of the oral mucosa (including aphthae and ulcers). The spectrum of histopathological changes ranges from nonspecific ulcerations to lichenoid reactions. Treatment of oral lesions induced by low doses of MTX consists in drug withdrawal or dose tapering. Folic acid and local symptomatic therapy can also be used, if necessary. Practitioners should be aware of the potential development of MTX-induced oral lesions, and specific aspects of the drug pharmacokinetics and pharmacodynamics in order to be able to ensure timely detection of adverse reactions and their effective treatment.

Scabies: Transcutaneous Poisoning During Treatment

PEDIATRICS ◽  
1977 ◽  
Vol 59 (4) ◽  
pp. 643-643 ◽  
Author(s):  
Beulah Lee ◽  
Paul Groth
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Side Effects ◽  
Health Professionals ◽  
Adverse Reactions ◽  
Drug Experience ◽  
American Academy Of Pediatrics ◽  
Benzene Hexachloride ◽  
Cns Side Effects ◽  
High Doses

The FDA Drug Bulletin (6:28, 1976) alerted physicians and other health professionals to the possibility of adverse central nervous system (CNS) side effects, particularly in children, that may occur from high doses of the commonly employed scabicides. The American Academy of Pediatrics has requested its members to report adverse reactions from scabicides to the AAP, which, in turn, will keep the FDA informed. Following the FDA Drug Bulletin alert and the announcement by the AAP, the FDA's Division of Drug Experience received the following clinical reports of suspected CNS toxicity to gamma benzene hexachloride (GBH, Kwell, Gamene, lindane).

Advanced Age as a Risk Factor of Drug-Induced Diseases

2021 ◽  
Vol 9 (1) ◽  
pp. 15-24
Author(s):  
D. A. Sychev ◽  
O. D. Ostroumova ◽  
A. P. Pereverzev ◽  
A. I. Kochetkov ◽  
T. M. Ostroumova ◽  
...  
Keyword(s):  
Adverse Reactions ◽  
Healthcare Professionals ◽  
Scientific Literature ◽  
Liver Volume ◽  
Natural Aging ◽  
Older Age ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Drug Induced ◽  
Age Related ◽  
Filtration Capacity

Some patients are more likely to have drug-induced diseases due to a number of risk factors, such as older age. The aim of the study was to analyse the effect of older age on pharmacokinetics and pharmacodynamics of medicines and the risk of developing drug-induced diseases. The analysis of scientific literature demonstrated that changes in the functions of body organs and systems caused by natural aging processes may potentially affect pharmacokinetics and pharmacodynamics of medicines and increase the risk of adverse drug reactions. For instance, older people have a decreased cardiac output both at rest and during exercise, weight loss, loss of elasticity of elastic vessels, a reduced number of functioning nephrons, poorer renal filtration capacity, decreased liver volume, a reduced number of functioning hepatocytes, decreased hepatic blood flow. These changes directly affect absorption, metabolism, distribution, and excretion of medicines, which in turn can affect their safety profiles. Consideration of age-related changes in the functions of body organs and systems, regular monitoring of the efficacy and safety of the prescribed medicine, changing the dosage regimen, and revision of the treatment sheet by healthcare professionals will help optimize pharmacotherapy and reduce the risk of adverse reactions and drug-induced diseases in older patients.

scholarly journals Cosmetic Use-Related Adverse Events: Findings from Lay Public in Malaysia

Cosmetics ◽  
2020 ◽  
Vol 7 (2) ◽  
pp. 41
Author(s):  
Hazrina Hadi ◽  
Nur’ain Ai ◽  
Mazlina Zamli ◽  
Ammar Ihsan Awadh ◽  
Muhammad Zeeshan Zafar ◽  
...  
Keyword(s):  
Social Sciences ◽  
Health Professionals ◽  
Adverse Reactions ◽  
Study Data ◽  
Adverse Outcomes ◽  
Cosmetic Products ◽  
Cross Sectional ◽  
Facial Area ◽  
Lay Public ◽  
Structured Questionnaire

Objectives: Although the occurrence of adverse cosmetic reactions is often underestimated by the consumers, the documentation of the incident might be helpful for the authority in regulating the cosmetic products. The objectives of this study were to assess the prevalence and type of adverse cosmetic event (ACE), as well as the measures adopted by those experiencing the ACE. Methods: A cross-sectional descriptive study was conducted using a structured questionnaire comprised of 11 questions. The questionnaire was divided into two sections: demographic profile and adverse cosmetic reaction. A total of 552 cosmetic users in Malaysia participated in this study. Data were entered into Statistical Package for Social Sciences (SPSS) version 20 and descriptive statistics was applied. Findings: A total of 29% respondents have experienced ACEs. Eczema was found to be the most frequent type of ACE. Facial area (n = 178) was reported to be the most frequent body site affected by ACEs. A mere 41% attempted to consult health professionals. Conclusions: Few respondents consulted health professionals for recommendations, indicating that they misjudge occurrences related to adverse outcomes. The high diversity and non-specificity of cosmetic adverse reactions reported in the current research highlighted the need for a vigorous cosmetovigilance system.

Tartrazine-Containing Drugs

1981 ◽  
Vol 15 (10) ◽  
pp. 782-788 ◽  
Author(s):  
Mary Lee ◽  
Anne Fondriest Gentry ◽  
Rowena Schwartz ◽  
Jerry Bauman
Keyword(s):  
General Population ◽  
Prescription Drugs ◽  
Health Professionals ◽  
Adverse Reactions ◽  
Over The Counter ◽  
Current List ◽  
A Current

Although the incidence of tartrazine sensitivity in the general population is low, serious adverse reactions have occurred. To prevent unnecessary exposure of sensitive patients, physicians should avoid prescribing tartrazine-containing drugs. Because of new FDA requirements that manufacturers list tartrazine dye in both over-the-counter and prescription drugs, many manufacturers have reformulated their products to remove this colorant. Therefore, previously published lists of tartrazine-containing drugs are outdated. We conducted a survey of American manufacturers to derive a current list of tartrazine-containing drugs. This list is intended for use as a guide for health professionals who wish to avoid products containing tartrazine in prescribing for patients sensitive to it.

The next generation of machine learning in DDIs prediction

2021 ◽  
Vol 27 ◽  
Author(s):  
Wei Huang ◽  
Chunyan Li ◽  
Ying Ju ◽  
Yan Gao
Keyword(s):  
Drug Interactions ◽  
Adverse Reactions ◽  
Computational Method ◽  
New Drugs ◽  
Computational Techniques ◽  
Data Sets ◽  
Review Of The Literature ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Challenges And Opportunities ◽  
Drug Assays

: Drug-drug interactions may occur when to combine two or more drugs and may cause some adverse events such as Cardiotoxicity, Central neurotoxicity, Hepatotoxicity, etc. Although a large number of researchers who are proficient in pharmacokinetics and pharmacodynamics have been engaged in drug assays and trying to find out the side effects of all kinds of drug combinations. However, at the same time, the number of new drugs is increasing dramatically, and the drug assay is an expensive and time-consuming process. It is impossible to find all the adverse reactions through drug experiments. Therefore, new attempts have risen in using computational techniques to deal with this problem. In this review, we conduct a review of the literature on applying the computational method for predicting drug-drug interactions. We first briefly introduce the widely used data sets. After that, we elaborate on the existing state-of-art deep learning models for drug-drug interactions prediction. We also discussed the challenges and opportunities of applying the computational method in drug-drug interactions prediction.

Effects of pharmacogenetic variants on vemurafenib-related toxicities in patients with melanoma

2019 ◽  
Vol 20 (18) ◽  
pp. 1283-1290
Author(s):  
Andrew KL Goey ◽  
Mirjam de With ◽  
Bram C Agema ◽  
Esther Oomen-De Hoop ◽  
Rajbir K Singh ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Genetic Variants ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Interpatient Variability ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Increased Risk ◽  
Melanoma Patients ◽  
Grade 3 ◽  
Polymorphic Enzymes

Aim: The pharmacokinetics and pharmacodynamics of vemurafenib are characterized by a wide interpatient variability. Since multiple polymorphic enzymes and drug transporters are involved in vemurafenib pharmacokinetics, we studied associations of polymorphisms on vemurafenib-associated toxicities. Patients & methods: Prospectively collected samples of 97 melanoma patients treated with vemurafenib alone (n = 62) or in combination with cobimetinib (n = 35) were genotyped for ABCB1 (3435C>T), ABCG2 (421C>A, 34G>A) and CYP3A4 ( *22, 15389C>T) polymorphisms. Associations between these variants and the incidence of toxicities were studied. Results: CYP3A4*22 was significantly associated with increased risk for grade ≥3 nausea, grade 1–4 hyperbilirubinemia, and cutaneous squamous cell carcinoma. ABCB1 3435C>T was a predictor for grade ≥3 toxicity. Conclusion: Genetic variants in CYP3A4 and ABCB1 are associated with vemurafenib-associated toxicities.

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