Pub Date : 2021-11-08DOI: 10.5772/intechopen.99328
Abdulmohsen H. Alrohaimi, Bader Alrohaimi, Nada H. Alruwais, Kholoud Aldmasi
The cytochromes P450 (CYPs) are a group of enzymes that are primarily responsible for oxidative drug biotransformation in people. CYP2B6, which metabolizes numerous drugs including bupropion, propofol and other drug shows great variability in rates of drug oxidation between individuals. In this chapter we discuss the contribution of selected genetic and environmental factors to this variability. Several studies identified and quantified the most common CYP2B6 mRNA splice such as deletion of exons 4 to 6 and of exon 4 which were significantly and negatively correlated with CYP2B6 protein and enzyme activity. CYP2B6 gene expression is highly inducible by phenobarbital. Alcohol ingestion has been associated with increased CYP2B6 levels this involves the constitutive androstane receptor (CAR) and/or the pregnane X receptor (PXR). CYP2B7 is considered a pseudogene because of the presence of a single premature stop codon (TGA) in exon 7. In 10 out of 24 African-Americans (but none out of 48 European-Americans) there is a single nucleotide polymorphism that results in an arginine codon instead of a stop codon (X378R). The results of these studies identify certain CYP2B6 genetic polymorphisms, mRNA splicing variants, and alcohol ingestion as significant factors that determine interindividual variability of CYP2B-mediated oxidation of drugs in people.
{"title":"Interindividual Variability of Cytochromes P450 2B Mediated Oxidation in Human Liver","authors":"Abdulmohsen H. Alrohaimi, Bader Alrohaimi, Nada H. Alruwais, Kholoud Aldmasi","doi":"10.5772/intechopen.99328","DOIUrl":"https://doi.org/10.5772/intechopen.99328","url":null,"abstract":"The cytochromes P450 (CYPs) are a group of enzymes that are primarily responsible for oxidative drug biotransformation in people. CYP2B6, which metabolizes numerous drugs including bupropion, propofol and other drug shows great variability in rates of drug oxidation between individuals. In this chapter we discuss the contribution of selected genetic and environmental factors to this variability. Several studies identified and quantified the most common CYP2B6 mRNA splice such as deletion of exons 4 to 6 and of exon 4 which were significantly and negatively correlated with CYP2B6 protein and enzyme activity. CYP2B6 gene expression is highly inducible by phenobarbital. Alcohol ingestion has been associated with increased CYP2B6 levels this involves the constitutive androstane receptor (CAR) and/or the pregnane X receptor (PXR). CYP2B7 is considered a pseudogene because of the presence of a single premature stop codon (TGA) in exon 7. In 10 out of 24 African-Americans (but none out of 48 European-Americans) there is a single nucleotide polymorphism that results in an arginine codon instead of a stop codon (X378R). The results of these studies identify certain CYP2B6 genetic polymorphisms, mRNA splicing variants, and alcohol ingestion as significant factors that determine interindividual variability of CYP2B-mediated oxidation of drugs in people.","PeriodicalId":190619,"journal":{"name":"Pharmacogenetics [Working Title]","volume":"163 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122011366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-18DOI: 10.5772/INTECHOPEN.97643
Ruchi Chawla, V. Rani, Mohini Mishra, Krishan Kumar
“One size fits all” is an erroneous paradigm in drug delivery, due to side effects/adverse effects and variability observed in drug response. The variability is a result of geneotypic variations (variability in genomic constitution) which is studied in the branch of science called Pharmacogenomics. The variability in drug response is studied by multigene analysis or profiling of whole-genome single nucleotide polymorphism (SNP) and is recorded in terms of the pharmacokinetic (absorption, distribution, metabolism and elimination) and pharmacodynamic (drug-receptor interaction, immune response, etc.) response of the drug. Therefore, a foray into this research area can provide valuable information for designing of drug therapies, identifying disease etiology, therapeutic targets and biomarkers for application in treatment and diagnosis of diseases. Lately, with the integration of pharmacogenomics and nanotechnology, a new facade for the diagnosis and treatment of diseases has opened up, and the prescription pattern of drugs has moved to pharmacotyping (individualized dose and dosage-form adjusted therapy) using nanoplatforms like nanobioconjugates, nanotheranostics, etc.
{"title":"Integrated Role of Nanotechnology and Pharmacogenetics in Diagnosis and Treatment of Diseases","authors":"Ruchi Chawla, V. Rani, Mohini Mishra, Krishan Kumar","doi":"10.5772/INTECHOPEN.97643","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.97643","url":null,"abstract":"“One size fits all” is an erroneous paradigm in drug delivery, due to side effects/adverse effects and variability observed in drug response. The variability is a result of geneotypic variations (variability in genomic constitution) which is studied in the branch of science called Pharmacogenomics. The variability in drug response is studied by multigene analysis or profiling of whole-genome single nucleotide polymorphism (SNP) and is recorded in terms of the pharmacokinetic (absorption, distribution, metabolism and elimination) and pharmacodynamic (drug-receptor interaction, immune response, etc.) response of the drug. Therefore, a foray into this research area can provide valuable information for designing of drug therapies, identifying disease etiology, therapeutic targets and biomarkers for application in treatment and diagnosis of diseases. Lately, with the integration of pharmacogenomics and nanotechnology, a new facade for the diagnosis and treatment of diseases has opened up, and the prescription pattern of drugs has moved to pharmacotyping (individualized dose and dosage-form adjusted therapy) using nanoplatforms like nanobioconjugates, nanotheranostics, etc.","PeriodicalId":190619,"journal":{"name":"Pharmacogenetics [Working Title]","volume":"14 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132578884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-04-26DOI: 10.5772/INTECHOPEN.97498
Munindra Ruwali, Keshav Moharir, Sanjiv Singh, P. Aggarwal, M. Paul
Though significant clinical advances have been made, lung cancer remains the most lethal, with a low 5-year survival rate. The variability in patient response towards therapy is substantial and is associated with lung cancer’s genomic landscape. Pharmacogenetic studies have deciphered many clinically relevant associations between tumor genetic alterations and their influences on drug efficacy, toxicity sensitivity and overall outcomes of cancer treatment. Biomarkers are tools in the arsenal that can help in the prediction, prognosis, diagnosis and follow-up of cancer treatment. Bulk and single-cell next-generation sequencing of large patient cohorts have generated a better understanding of the genetic underpinnings of lung cancer, and opening up personalized therapeutic opportunities. Immunotherapy and personalized medicine are providing hope for lung cancer patients. This review highlights the genetic alterations and important lung cancer biomarkers. The pharmacogenetic associations, personalized immunotherapy and challenges associated with effective therapy are also discussed. Pharmacogenetics and pharmacogenomics can open up new vistas for optimized, personalized NSCLC treatment.
{"title":"Updates in Pharmacogenetics of Non-Small Cell Lung Cancer","authors":"Munindra Ruwali, Keshav Moharir, Sanjiv Singh, P. Aggarwal, M. Paul","doi":"10.5772/INTECHOPEN.97498","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.97498","url":null,"abstract":"Though significant clinical advances have been made, lung cancer remains the most lethal, with a low 5-year survival rate. The variability in patient response towards therapy is substantial and is associated with lung cancer’s genomic landscape. Pharmacogenetic studies have deciphered many clinically relevant associations between tumor genetic alterations and their influences on drug efficacy, toxicity sensitivity and overall outcomes of cancer treatment. Biomarkers are tools in the arsenal that can help in the prediction, prognosis, diagnosis and follow-up of cancer treatment. Bulk and single-cell next-generation sequencing of large patient cohorts have generated a better understanding of the genetic underpinnings of lung cancer, and opening up personalized therapeutic opportunities. Immunotherapy and personalized medicine are providing hope for lung cancer patients. This review highlights the genetic alterations and important lung cancer biomarkers. The pharmacogenetic associations, personalized immunotherapy and challenges associated with effective therapy are also discussed. Pharmacogenetics and pharmacogenomics can open up new vistas for optimized, personalized NSCLC treatment.","PeriodicalId":190619,"journal":{"name":"Pharmacogenetics [Working Title]","volume":"12 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133427577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-02-18DOI: 10.5772/INTECHOPEN.95966
N. Shnayder, M. Petrova, E. Bochanova, O. V. Zimnitskaya, A. Savinova, E. Pozhilenkova, R. Nasyrova
For more than 50 years, oral vitamin K antagonists were the choice of anticoagulant for the long-term treatment and prevention of arterial and venous thromboembolic events. In recent years, four direct oral anticoagulants (DOACs), dabigatran, rivaroxaban, apixaban and edoxaban have been compared with warfarin for thromboembolism prevention. These anticoagulants directly inhibit specific proteins within the coagulation cascade; in contrast, oral vitamin K antagonists inhibit the synthesis of vitamin K-dependent clotting factors. Dabigatran, a direct thrombin inhibitor, and rivaroxaban, apixaban and edoxaban, the factor Xa inhibitors, produce a more predictable, less labile anticoagulant effect. DOACs do not have limitations inherent vitamin K antagonists. DOACs have a predictable pharmacokinetic profile and are free of advers drugs reactions inherent in vitamin K antagonists. However, it is necessary to take into account the pharmacogenetic characteristics of the individual that can affect effectiveness and safety of use of DOACs. The results carried out to the present fundamental and clinical studies of DOACs studies demonstrate an undeniable the influence of genome changes on the pharmacokinetics and pharmacodynamics of DOACs. However, the studies need to be continued. There is a need to plan and conduct larger studies in various ethnic groups with the inclusion of sufficient associative genetic studies of the number of patients in each of the documented groups treatments with well-defined phenotypes.
{"title":"Pharmacogenetics of Direct Oral Anticoagulants","authors":"N. Shnayder, M. Petrova, E. Bochanova, O. V. Zimnitskaya, A. Savinova, E. Pozhilenkova, R. Nasyrova","doi":"10.5772/INTECHOPEN.95966","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.95966","url":null,"abstract":"For more than 50 years, oral vitamin K antagonists were the choice of anticoagulant for the long-term treatment and prevention of arterial and venous thromboembolic events. In recent years, four direct oral anticoagulants (DOACs), dabigatran, rivaroxaban, apixaban and edoxaban have been compared with warfarin for thromboembolism prevention. These anticoagulants directly inhibit specific proteins within the coagulation cascade; in contrast, oral vitamin K antagonists inhibit the synthesis of vitamin K-dependent clotting factors. Dabigatran, a direct thrombin inhibitor, and rivaroxaban, apixaban and edoxaban, the factor Xa inhibitors, produce a more predictable, less labile anticoagulant effect. DOACs do not have limitations inherent vitamin K antagonists. DOACs have a predictable pharmacokinetic profile and are free of advers drugs reactions inherent in vitamin K antagonists. However, it is necessary to take into account the pharmacogenetic characteristics of the individual that can affect effectiveness and safety of use of DOACs. The results carried out to the present fundamental and clinical studies of DOACs studies demonstrate an undeniable the influence of genome changes on the pharmacokinetics and pharmacodynamics of DOACs. However, the studies need to be continued. There is a need to plan and conduct larger studies in various ethnic groups with the inclusion of sufficient associative genetic studies of the number of patients in each of the documented groups treatments with well-defined phenotypes.","PeriodicalId":190619,"journal":{"name":"Pharmacogenetics [Working Title]","volume":"57 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132382621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-01-29DOI: 10.5772/INTECHOPEN.95751
José Antonio Diniz de Oliveira
In Medical Nemesis - The expropriation of health, IVAN ILLICH highlights several aspects of the medicalization of society, which was already observed in the mid-1970s. He addressed the various forms of iatrogenesis, classifying the new disease caused by the set of medical care as an epidemic that would not exist if there were no medical intervention. Of the various forms of iatrogenesis, he also addressed drug iatrogenesis, including the cause of hospital admissions. In this article, more than 40 years after Illich’s seminal publication, we sought to revisit his thinking and assess the relevance of his narrative regarding the inconveniences resulting from the use of medicines, especially in their impacts on hospitalization, in addition to reflecting on the potential of pharmacogenetics to mitigate adverse events related to drugs that victimize people. After a brief presentation of Illich’s trajectory, a digression is made on the association between the concepts of medicalization and iatrogenesis, to then make quick considerations about social iatrogenesis, considering the effects of this phenomenon on society. After presenting the consequences of iatrogenesis, from a fluent literature review, an update of the findings is made, showing that the problem is relevant today. A brief conceptual presentation of pharmacogenetics is followed by some examples of its clinical consequences. It is concluded that, despite the unequivocal importance of pharmacotherapy, iatrogenesis remains a problem of increasing relevance. Pharmacogenetics presents itself as a possibility to minimize the problem, making it possible to expand its use in the practice of medical services.
{"title":"Ivan Illich, Iatrogenesis and Pharmacogenetics","authors":"José Antonio Diniz de Oliveira","doi":"10.5772/INTECHOPEN.95751","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.95751","url":null,"abstract":"In Medical Nemesis - The expropriation of health, IVAN ILLICH highlights several aspects of the medicalization of society, which was already observed in the mid-1970s. He addressed the various forms of iatrogenesis, classifying the new disease caused by the set of medical care as an epidemic that would not exist if there were no medical intervention. Of the various forms of iatrogenesis, he also addressed drug iatrogenesis, including the cause of hospital admissions. In this article, more than 40 years after Illich’s seminal publication, we sought to revisit his thinking and assess the relevance of his narrative regarding the inconveniences resulting from the use of medicines, especially in their impacts on hospitalization, in addition to reflecting on the potential of pharmacogenetics to mitigate adverse events related to drugs that victimize people. After a brief presentation of Illich’s trajectory, a digression is made on the association between the concepts of medicalization and iatrogenesis, to then make quick considerations about social iatrogenesis, considering the effects of this phenomenon on society. After presenting the consequences of iatrogenesis, from a fluent literature review, an update of the findings is made, showing that the problem is relevant today. A brief conceptual presentation of pharmacogenetics is followed by some examples of its clinical consequences. It is concluded that, despite the unequivocal importance of pharmacotherapy, iatrogenesis remains a problem of increasing relevance. Pharmacogenetics presents itself as a possibility to minimize the problem, making it possible to expand its use in the practice of medical services.","PeriodicalId":190619,"journal":{"name":"Pharmacogenetics [Working Title]","volume":"35 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131815459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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