scholarly journals Pharmacogenomics in depression and antidepressants

2005 ◽  
Vol 7 (3) ◽  
pp. 223-230
Keyword(s):  
Side Effects ◽  
Adverse Effects ◽  
Drug Response ◽  
Genetic Factors ◽  
Drug Action ◽  
Mechanisms Of Action ◽  
Drug Metabolizing Enzymes ◽  
Receptor Function ◽  
Metabolizing Enzymes ◽  
Adaptive Processes

Genetic factors are believed to play a major role in the variation of treatment response and the incidence of adverse effects to medication. The aim of pharmacogenetics is to elucidate this variability according to hereditary differences. Considering current hypotheses for the mechanisms of action of antidepressants, most investigations to date have concentrated on mutations in genes coding either for the pathways in the serotonergic and noradrenergic systems or for drug-metabolizing enzymes. Recent studies shifted the emphasis on the main mechanism of drug action from changes in neurotransmitter concentration or receptor function toward long-lasting adaptive processes within the neurons. Although the results are controversial, many studies support the hypothesis that psychopharmacogenetics will help predict an individual's drug response, while minimizing the side effects. The inclusion of functional genomics, which investigates the complex gene and/or protein expression in response to a given drug, may lead to the development of novel and safer drugs.

scholarly journals Pharmacogenetics of Antiplatelet Drugs

2002 ◽  
Vol 2 ◽  
pp. 791-800 ◽  
Author(s):  
Ronan Curtin ◽  
Desmond J. Fitzgerald
Keyword(s):  
Clinical Trials ◽  
Drug Targets ◽  
Genetic Factors ◽  
Adverse Outcome ◽  
Antiplatelet Agents ◽  
Genetic Variations ◽  
Antiplatelet Drugs ◽  
Drug Metabolizing Enzymes ◽  
Gene Variant ◽  
Metabolizing Enzymes

Pharmacogenetics refers to the genetic factors that influence the response to a drug, often involving genetic variations in drug metabolizing enzymes. The pharmacogenetics of antiplatelet agents is in its infancy and largely reflects variations in drug targets or related genes. One particular gene variant, the PlA2polymorphism of the glycoprotein (GP) IIb/IIIa receptor, is now emerging as a probable determinant of the response to antiplatelet agents including GPIIb/IIIa antagonists. This variant may in part explain the heterogeneity in the response to GPIIb/IIIa antagonists. The PlA2genotype appears to be associated with an adverse outcome in patients treated with an oral GPIIb/IIIa antagonist and may be a factor in the observed failure of these agents in unselected populations. However, there are preliminary indications that other antiplatelet agents may have an enhanced effect in PlA2subjects. Further clinical trials in particular are required to definitively characterize the pharmacogenetic effect of PlA2. Other polymorphisms are also likely to contribute to the pharmacogenetics of antiplatelet agents, but these await investigation.

Pharmacogenetics of common SNP affecting drug metabolizing enzymes: comparison of allele frequencies between European and Malaysian/Singaporean

2021 ◽  
Vol 36 (3) ◽  
pp. 173-181
Author(s):  
Nur Salwani Bakar
Keyword(s):  
Ethnic Diversity ◽  
Drug Response ◽  
Association Studies ◽  
Allele Frequencies ◽  
Drug Metabolizing Enzymes ◽  
Uridine Diphosphate ◽  
Metabolizing Enzymes ◽  
Single Nucleotide ◽  
Asian Populations ◽  
Two Populations

Abstract Compared to Europe, data on genetic variation in genes transcribing drug metabolizing enzymes among Asian is limited due to ethnic diversity. Here we compare frequencies for clinically relevant single nucleotide polymorphism (SNP) commonly observed in drug metabolizing enzymes between European and Malaysian/Singaporean. Minor allele frequencies (MAF) for the indicated SNPs for European, South Asian and East Asian populations were obtained from the NCBI website (https://www.ncbi.nlm.nih.gov/snp). The SNP prevalence among Malaysian/Singaporean was characterized from gene association studies. Generally, some SNPs in CYP2D6 and CYP2C19 do not show good agreement between the two populations as to the MAF value obtained. CYP2D6*4 tends to be more common among European, whereas CYP2D6*10 is more common in Malays and Chinese among Singaporean. Regardless of different phenotype, MAF of CYP2D6*4 for Indians is similar to that seen by the European. Singaporeans show smaller MAF for CYP2C19*17 but higher CYP2C19*2 frequencies as opposed to European ones. Following growing attention to the contribution of CYP3A4/5, N-acetyltransferases (NAT2), thiopurine methyltransferase (TPMT) and uridine diphosphate glucuronosyltransferases (UGT)2B7 in predicting drug response across Europe, there are limited pharmacogenetics (PGx) studies examining the gene-drug interaction among Malaysian/Singaporean. To better understand the heterogeneity of the drug response, PGx studies for the abovementioned enzymes between ethnics in Malaysian/Singaporean should be identified.

Do New Antiepileptic Drugs with Novel Mechanisms of Action Suggest Reconsideration of Rational Polypharmacy?

US Neurology ◽  
2010 ◽  
Vol 06 (01) ◽  
pp. 70 ◽  
Author(s):  
Barry E Gidal ◽  
Keyword(s):  
Side Effects ◽  
Adverse Effects ◽  
Mechanisms Of Action ◽  
Rational Approach ◽  
Effective Control ◽  
Partial Seizures ◽  
New Antiepileptic Drugs ◽  
Number Of Patients ◽  
Seizure Models ◽  
Pharmacologic Effect

Although effective control of epilepsy can be achieved by a single antiepileptic drug (AED), the condition persists in a significant number of patients despite increasing dosages with monotherapy and polytherapy. Treatment with combinations of older AEDs has been known to cause undesirable drug–drug interactions and side effects. However, there has been renewed interest in polytherapy with the advent of newer AEDs with novel mechanisms of actions that are less likely to cause adverse effects in patients. Animal seizure models are useful for determining whether AEDs will be effective in generalised or partial seizures prior to clinical studies and isobolgraphic analysis may allow for a more systematic, rational approach to predicting whether a given combination of drugs will result in a greater or lesser pharmacologic effect. Since one treatment strategy does not suit all patients, studies should focus on the tolerability and safety of specific combinations of AEDs in order to provide guidance to physicians. In summary, pharmacokinetic interactions must be taken into account in studies in humans and animals with measurement of toxicity as well as efficacy.

scholarly journals ADVERSE EFFECTS AND SIDE EFFECTS ON VITAMIN THERAPY: A REVIEW

2017 ◽  
Vol 10 (5) ◽  
pp. 19 ◽  
Author(s):  
Mejo C Korah ◽  
Junaid Rahman Pv ◽  
R Rajeswari ◽  
Ahana Behanan ◽  
Elizabeth Phoeba Paul ◽  
...  
Keyword(s):  
Side Effects ◽  
Adverse Effects ◽  
Health Professionals ◽  
Genetic Factors ◽  
Mortality Rates ◽  
Health Organizations ◽  
Major Health ◽  
Vitamin Therapy ◽  
Vitamin Uptake ◽  
Anti Hiv

Vitamins are essential to our day to day life. Its shortage in our body can cause many disorders, decreased enzyme activities also affects the genetic factors. Vitamins should be supplied through the diet in the required amount. If it is not supplied properly, vitamin tablets will be prescribed. And also vitamin tablets are the co-medication for therapies like anticancer, anti tubercular, anti viral anti HIV treatments. Many news papers reported that vitamin therapies are causing major health problems like nephro/ urolithiasis, it can increases mortality rates in smokers by increasing the risk of lung cancer, it can cause abortion when it is taken during pregnancy. Thus here we reviewed the adverse effects of vitamin therapy from various reported cases, books, instructions provided from various health organizations and also news papers and magazines. It can help health professionals to control and monitor the vitamin therapies and make awareness about the adverse effects and possible side effects of regular vitamin uptake to society.

scholarly journals Pharmacogenetics of drug-metabolizing enzymes: implications for a safer and more effective drug therapy

2005 ◽  
Vol 360 (1460) ◽  
pp. 1563-1570 ◽  
Author(s):  
Magnus Ingelman-Sundberg ◽  
Cristina Rodriguez-Antona
Keyword(s):  
Gene Expression ◽  
Cytochrome P450 ◽  
Drug Therapy ◽  
Adverse Effects ◽  
Drug Metabolism ◽  
Drug Metabolizing Enzymes ◽  
Drug Reactions ◽  
Metabolizing Enzymes ◽  
Drug Treatments ◽  
Polymorphic Enzymes

The majority of phase I- and phase II-dependent drug metabolism is carried out by polymorphic enzymes which can cause abolished, quantitatively or qualitatively decreased or enhanced drug metabolism. Several examples exist where subjects carrying certain alleles do not benefit from drug therapy due to ultrarapid metabolism caused by multiple genes or by induction of gene expression or, alternatively, suffer from adverse effects of the drug treatment due to the presence of defective alleles. It is likely that future predictive genotyping for such enzymes might benefit 15–25% of drug treatments, and thereby allow prevention of adverse drug reactions and causalities, and thus improve the health of a significant fraction of the patients. However, it will take time before this will be a reality within the clinic. We describe some important aspects in the field with emphasis on cytochrome P450 and discuss also polymorphic aspects of foetal expression of CYP3A5 and CYP3A7 .

scholarly journals Pharmacogenetics of Carbamazepine and Valproate: Focus on Polymorphisms of Drug Metabolizing Enzymes and Transporters

2021 ◽  
Vol 14 (3) ◽  
pp. 204
Author(s):  
Teresa Iannaccone ◽  
Carmine Sellitto ◽  
Valentina Manzo ◽  
Francesca Colucci ◽  
Valentina Giudice ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Drug Response ◽  
Current Knowledge ◽  
Individual Variability ◽  
Mood Stabilizers ◽  
Drug Metabolizing Enzymes ◽  
Efficacy And Safety ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Metabolizing Enzymes ◽  
Drug Pharmacokinetics

Pharmacogenomics can identify polymorphisms in genes involved in drug pharmacokinetics and pharmacodynamics determining differences in efficacy and safety and causing inter-individual variability in drug response. Therefore, pharmacogenomics can help clinicians in optimizing therapy based on patient’s genotype, also in psychiatric and neurological settings. However, pharmacogenetic screenings for psychotropic drugs are not routinely employed in diagnosis and monitoring of patients treated with mood stabilizers, such as carbamazepine and valproate, because their benefit in clinical practice is still controversial. In this review, we summarize the current knowledge on pharmacogenetic biomarkers of these anticonvulsant drugs.

Pharmacogenetics of common SNP affecting drug metabolizing enzymes: comparison of allele frequencies between European and Malaysian/Singaporean

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Nur Salwani Bakar
Keyword(s):  
Ethnic Diversity ◽  
Drug Response ◽  
Association Studies ◽  
Allele Frequencies ◽  
Drug Metabolizing Enzymes ◽  
Uridine Diphosphate ◽  
Metabolizing Enzymes ◽  
Single Nucleotide ◽  
Asian Populations ◽  
Two Populations

Abstract Compared to Europe, data on genetic variation in genes transcribing drug metabolizing enzymes among Asian is limited due to ethnic diversity. Here we compare frequencies for clinically relevant single nucleotide polymorphism (SNP) commonly observed in drug metabolizing enzymes between European and Malaysian/Singaporean. Minor allele frequencies (MAF) for the indicated SNPs for European, South Asian and East Asian populations were obtained from the NCBI website (https://www.ncbi.nlm.nih.gov/snp). The SNP prevalence among Malaysian/Singaporean was characterized from gene association studies. Generally, some SNPs in CYP2D6 and CYP2C19 do not show good agreement between the two populations as to the MAF value obtained. CYP2D6*4 tends to be more common among European, whereas CYP2D6*10 is more common in Malays and Chinese among Singaporean. Regardless of different phenotype, MAF of CYP2D6*4 for Indians is similar to that seen by the European. Singaporeans show smaller MAF for CYP2C19*17 but higher CYP2C19*2 frequencies as opposed to European ones. Following growing attention to the contribution of CYP3A4/5, N-acetyltransferases (NAT2), thiopurine methyltransferase (TPMT) and uridine diphosphate glucuronosyltransferases (UGT)2B7 in predicting drug response across Europe, there are limited pharmacogenetics (PGx) studies examining the gene-drug interaction among Malaysian/Singaporean. To better understand the heterogeneity of the drug response, PGx studies for the abovementioned enzymes between ethnics in Malaysian/Singaporean should be identified.

scholarly journals Genetic variation of pharmacogenes

2020 ◽  
Vol 18 (3) ◽  
pp. 393-416
Author(s):  
Vu Phuong Nhung ◽  
Nguyen Dang Ton ◽  
Nong Van Hai ◽  
Nguyen Hai Ha
Keyword(s):  
Genetic Variants ◽  
Drug Targets ◽  
Drug Response ◽  
Drug Transporters ◽  
Copy Number Variants ◽  
Drug Dose ◽  
Patient Specific ◽  
Specific Response ◽  
Drug Metabolizing Enzymes ◽  
Metabolizing Enzymes

Patient specific response against a particular drug could be affected by various factors, in which genetic factors are the most crucial contributor. The genetic variability in pharmacogenes might result in variable drug response of individuals, which in turn can lead to unexpected treatment outcomes or even adverse drug reactions. The pharmacogenes include of genes that encode for several proteins which divided into 3 main functional categories: drug metabolizing enzymes, drug transporters and receptor-drug targets. Genetic variants of genes coding for drug metabolizing enzymes phase I (CYP450), phase II (GSTs, UGT, TPMT) as well as drug transporters (ABC, SLCO) of numerous populations in global have been extensively studied. Among these, SNPs are the major contributor behind variants of pharmacogenes along with copy number variants. Furthermore, the clinical impact on drug response of common variants belonging to several important pharmacogenes has been well understood. On the other hand, information on the variant spectrum of genes encoding for receptor-drug targets as well as their physiological effects have remained limited. In recent years, along with computational methods, next generation sequencing technologies had been developed tremendously. These high throughput methods had greatly promoted the field of pharmacogenetic research through providing ability to detect novel and rare genetic variants. The data on genetic variants of pharmacogenes would be valuable for determining the responder and non-responder to medication during treatment. These are also significant basis which play a vital role in development of the field of optimizing drug dose for individuals and personalized medicine in the future.

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