scholarly journals The Influence of Pharmacogenetics on the Clinical Relevance of Pharmacokinetic Drug–Drug Interactions: Drug–Gene, Drug–Gene–Gene and Drug–Drug–Gene Interactions

2021 ◽  
Vol 14 (5) ◽  
pp. 487
Author(s):  
Martina Hahn ◽  
Sibylle C. Roll
Keyword(s):  
Drug Therapy ◽  
Drug Interactions ◽  
Clinical Relevance ◽  
Adverse Drug Events ◽  
Current Evidence ◽  
Drug Event ◽  
Gene Interactions ◽  
Genetic Profile ◽  
The Impact ◽  
Pharmacokinetic Drug

Drug interactions are a well-known cause of adverse drug events, and drug interaction databases can help the clinician to recognize and avoid such interactions and their adverse events. However, not every interaction leads to an adverse drug event. This is because the clinical relevance of drug–drug interactions also depends on the genetic profile of the patient. If inhibitors or inducers of drug metabolising enzymes (e.g., CYP and UGT) are added to the drug therapy, phenoconcversion can occur. This leads to a genetic phenotype that mismatches the observable phenotype. Drug–drug–gene and drug–gene–gene interactions influence the toxicity and/or ineffectivness of the drug therapy. To date, there have been limited published studies on the impact of genetic variations on drug–drug interactions. This review discusses the current evidence of drug–drug–gene interactions, as well as drug–gene–gene interactions. Phenoconversion is explained, the and methods to calculate the phenotypes are described. Clinical recommendations are given regarding the integratation of the PGx results in the assessment of the relevance of drug interactions in the future.

Drug-related problems with targeted/immunotherapies at an oncology outpatient clinic

2019 ◽  
Vol 26 (3) ◽  
pp. 595-602
Author(s):  
Esra Kucuk ◽  
Aygin Bayraktar-Ekincioglu ◽  
Mustafa Erman ◽  
Saadettin Kilickap
Keyword(s):  
Adverse Drug Event ◽  
Clinical Pharmacist ◽  
Adverse Drug Events ◽  
Drug Event ◽  
Targeted Chemotherapy ◽  
Drug Related Problems ◽  
Patients With Cancer ◽  
Common Drug ◽  
Oncology Care ◽  
The Impact

Background Some studies in the literature describe drug-related problems in patients with cancer, although few studies focused on patients receiving targeted chemotherapy and/or immunotherapy. To identify the incidence of drug-related problems in patients receiving targeted chemotherapy and/or immunotherapy, and demonstrate the impact of a clinical pharmacist in an outpatient oncology care setting. Methods Prospective study was conducted in a hospital outpatient oncology clinic between October 2015 and March 2016. Patients greater than 18 years old receiving cetuximab, nivolumab, ipilimumab, or pembrolizumab were included in the study and monitored over a three-month period by a clinical pharmacist. Drug-related problems were analyzed using the Pharmaceutical Care Network Europe classification system. The main outcome measures were the frequency and causes of drug-related problems and the degree of resolution achieved through the involvement of a clinical pharmacist. Results A total of 54 patients (mean age: 57 ± 12 years) were included. There were 105 drug-related problems and 159 associated causes. Among the planned interventions (n = 149), 92 interventions were at the patient-level with 88 (96%) being accepted by the doctors. This resulted in 68 (65%) drug-related problems being completely resolved and 9 (8.6%) being partially resolved. The most common drug-related problem identified was “adverse drug event” (n = 38, 36%). Of the 105 drug-related problems, 63 (60%) related to targeted chemotherapy and/or immunotherapy with 34 (54%) classified as an “adverse drug event.” Conclusion Adverse drug events were the most common drug-related problems in patients with cancer. The involvement of a clinical pharmacist improved the identification of drug-related problems and helped optimize treatment outcomes in patients receiving targeted chemotherapy/immunotherapy.

scholarly journals 155 Polypharmacy Burden: How to Optimise, a Practical Approach

2019 ◽  
Vol 48 (Supplement_4) ◽  
pp. iv34-iv39
Author(s):  
Renukha Sellappans ◽  
Anand Prakash ◽  
Ahlam Sundus
Keyword(s):  
Drug Therapy ◽  
Medication Review ◽  
Older Persons ◽  
Adverse Drug Events ◽  
Healthcare Utilisation ◽  
Good Evidence ◽  
Clinical Indication ◽  
Practical Recommendation ◽  
The World ◽  
The Impact

Abstract Polypharmacy refers to the numerical value of medications used by a patient and is typically described as the concurrent use of five or more medications per day, but the definition is variable and there is no global consensus. Polypharmacy is unfortunate consequence of rapid advancement of medicine. Polypharmacy could be appropriate or problematic. Problematic polypharmacy can arise if the medicines are used without good evidence and in this situation risk of harm outweighs benefit. While there might be clinical indication for the medications to treat co-morbidities of a given patient, polypharmacy in older persons are associated with negative outcomes such as falls, adverse drug events and increased healthcare utilisation. This is mainly due to the physiological changes in this population which increases their risk of adverse drug events as well as the problems associated with remembering, managing and administering the medications appropriately. Hence, researchers and clinicians around the world have been actively looking at ways to reduce polypharmacy and optimise drug therapy in older persons to improve clinical, economic and social outcomes. To date, medication review by pharmacists in various settings has been the most researched and documented evidence in tackling this issue. Medication review refers to the structured evaluation of a patient’s medication with the aim to reach agreement with the patient about drug therapy, optimising the impact of medication, and minimising the number of drug-related problems. This session aims to summarise the available evidence on various types and outcomes of medication review with the aim to optimise polypharmacy among older persons around the world and provide a practical recommendation in tackling the phenomena.

Identification and evaluation of potentially inappropriate medications (PIMs) in hospitalized geriatric patients using Beers criteria

2015 ◽  
Vol 26 (4) ◽  
Author(s):  
Pattani Danisha ◽  
Chandrasekhar Dilip ◽  
Panakkal Linu Mohan ◽  
Cholamugath Shinu ◽  
Jaffer Chalil Parambil ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Geriatric Patients ◽  
Adverse Drug Events ◽  
Inappropriate Medication ◽  
Drug Event ◽  
Beers Criteria ◽  
Potentially Inappropriate Medications ◽  
Close Monitoring ◽  
Entire Study ◽  
Hospitalized Elderly

AbstractThe aim of the study was to identify and evaluate potentially inappropriate medication (PIM) in geriatric patients using Beers criteria and also to identify adverse drug events (ADEs) due to PIMs and various drug-drug interactions.The medications in the prescriptions of patients above 60 years of age, their dosage regimen respective of their diagnosis were analyzed. Each medication was then checked with Beers list tables, and any medication if mentioned in the Beers list, was noted along with its strength of recommendation and quality of evidence. Any adverse drug event (ADE) due to PIM was identified. Causality of the events was assessed by Naranjo’s Scale. The number of drug-drug interactions per prescription and the severity of each interaction were also analyzed. The collected data from 200 subjects were subjected to statistical treatments using Statistical Package for Social Sciences (SPSS) software version 16.0 for WINDOWS.Based on the Beers criteria 2012, 106 out of 200 (53%) prescriptions had at least one PIM prescribed. A sum of 1690 medications was prescribed as a whole for the entire study subjects. Among which, 134 PIMs were identified. Most commonly prescribed PIMs were benzodiazepines (39, 19.5%), followed by sliding scale use of insulin (31, 15.5%), and prazosin at a rate of 11.5% (23). A total of 10 ADEs were identified during the study. The average number of drug interactions observed among total samples was found to be 3.0±6.0 with 0±5.0 serious interactions, 2±4.0 significant interactions requiring close monitoring, and 0±6.0 minor interactions.The study shows high prevalence of prescribing PIMs in hospitalized elderly patients; PIM also caused incidence of ADEs; and serious drug-drug interactions were scarce among the patients.

scholarly journals Drug Prescribing to the Elderly Patients

2018 ◽  
Vol 1 (2) ◽  
pp. 65
Author(s):  
Misha’l Aly A
Keyword(s):  
Elderly Patients ◽  
Drug Interactions ◽  
Adverse Drug Event ◽  
Older Patients ◽  
Adverse Drug Events ◽  
The Elderly ◽  
Health Sciences ◽  
Drug Event ◽  
Drug Prescribing ◽  
Age Related

Age-related physiologic and anatomic changes in various body systems are accompanied by significant pharmacokinetic and pharmacodynamic alterations that make it mandatory for treating physicians to adjust types and dosages of medications for their older patients. Moreover, physicians should be always alert for adverse drug events, and consider any new symptoms as drug-related until proven otherwise. Other issues addressed include prescribing cascades, polypharmacy, drug-drug interactions, and the need to review all medications used by the elderly patients, with special attention to non-prescription and herbetic drugs. This review aims at maximizing safe medicine prescribing, and minimizing adverse drug event in caring for older subjects.International Journal of Human and Health Sciences Vol. 01 No. 02 July’17. Page : 65-69

scholarly journals Drug–drug–gene interactions and adverse drug reactions

2019 ◽  
Vol 20 (3) ◽  
pp. 355-366 ◽  
Author(s):  
Mustafa Adnan Malki ◽  
Ewan Robert Pearson
Keyword(s):  
Genetic Variation ◽  
Drug Interactions ◽  
Adverse Drug Reactions ◽  
Outcome Data ◽  
Gene Interactions ◽  
Drug Reactions ◽  
Health Burden ◽  
Detailed Classification ◽  
Important Drug ◽  
Pharmacokinetic Drug

AbstractThe economic and health burden caused by adverse drug reactions has increased dramatically in the last few years. This is likely to be mediated by increasing polypharmacy, which increases the likelihood for drug–drug interactions. Tools utilized by healthcare practitioners to flag potential adverse drug reactions secondary to drug–drug interactions ignore individual genetic variation, which has the potential to markedly alter the severity of these interactions. To date there have been limited published studies on impact of genetic variation on drug–drug interactions. In this review, we establish a detailed classification for pharmacokinetic drug–drug–gene interactions, and give examples from the literature that support this approach. The increasing availability of real-world drug outcome data linked to genetic bioresources is likely to enable the discovery of previously unrecognized, clinically important drug–drug–gene interactions.

scholarly journals Causation of potential drug to drug interactions alerts, alert overrides, and adverse drug events

2021 ◽  
Author(s):  
Aminah Mazyin Mohamed Ariff ◽  
Sivalingam Nalliah ◽  
Hafidz Abd Hadi ◽  
Nay Thu Win ◽  
Mohamed Imran Thoulath ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Critically Ill ◽  
Adverse Drug Events ◽  
Cardiac Patients ◽  
Drug Event ◽  
Potential Ddis ◽  
Preventive Actions ◽  
The Relationship ◽  
Related Harm ◽  
Cardiac Care Unit

Abstract Background: Drug-drug interactions (DDIs) leading to adverse drug event (ADEs) are of special interest because they represent preventable medication errors. Preventable ADE can result in errors involving the manifestation of adverse patient outcomes. Given the high complexity of critically ill cardiac patients, it is important to learn how CDDSS affects outcomes in this population and the number of alerts that likely be safely suppressed. Purpose: Identify adverse DDIs that is clinically detected and review the appropriateness of the doctor’s actions to the potential DDIs (PDDIs) alert. Study Design: This is a prospective observational study conducted at critical cardiac care unit (CCU) in a selected tertiary cardiac center for a duration of six months. Methods: Physicians treating critically ill cardiac patients were presented with PDDIs data which were acquired from two commercially available CDDSS. The relationship between the decision to prescribe and factors hypothesized to affect physicians' decisions were examined. Results: Evaluation of 709 patient medication profiles were conducted, resulting in 521 assessed patient profiles having had one or more PDDIs with 87% of them were influenced by polypharmacy. Ninety-one patients (17.5%) were associated with one or more adverse DDIs. Of the total 3284 potential DDIs alerts, 95.5% of the alerts were overridden. Preventable ADE as an outcome of inappropriate override have resulted 83.1 %. (236/284) of adverse DDIs. Whereas, appropriate overrides as an outcome of clinically irrelevant ADE were 16.9 % (48/284). Conclusion: Poor preventive actions taken by the doctors caused drug related harm to the patients despite having CDDSS in place. This suggests that CDDSS is an important application to minimize the harm associated with adverse DDIs by alerting physicians of potentially unsafe situations.

Clinical Implications of Antidepressant Pharmacokinetics and Pharmacogenetics

1996 ◽  
Vol 30 (12) ◽  
pp. 1471-1480 ◽  
Author(s):  
Lawrence J Cohen ◽  
C Lindsay DeVane
Keyword(s):  
Drug Therapy ◽  
Drug Interactions ◽  
English Language ◽  
Plasma Concentrations ◽  
Antidepressant Drug ◽  
Clinical Implications ◽  
Medline Search ◽  
Phenotypic Differences ◽  
Pharmacologic Agents ◽  
The Impact

OBJECTIVE: To review available data on pharmacokinetic and pharmacogenetic influences on the response to antidepressant therapy, analyze the mechanisms for and clinical significance of pharmacokinetic and pharmacogenetic differences, and explain the implications of pharmacokinetics and pharmacogenetics for patient care. DATA SOURCES: A MEDLINE search of English-language clinical studies, abstracts, and review articles on antidepressant pharmacokinetics, pharmacogenetics, and drug interactions was used to identify pertinent literature. DATA SYNTHESIS: The pharmacokinetic profiles of selected antidepressants are reviewed and the impact of hepatic microsomal enzymes on antidepressant metabolism is considered. How phenotypic differences influence the metabolism of antidepressant drug therapy is addressed. To evaluate the clinical implications of these pharmacokinetic and pharmacogenetic considerations, the findings of studies designed to elucidate drug interactions involving antidepressant agents are discussed. CONCLUSIONS: Differences in antidepressant plasma concentrations, and possibly safety, are caused by polymorphism in the genes that encode some of the cytochrome P450 isoenzymes that metabolize antidepressants. The isoenzymes 1A2, 2C9/19, 2D6, and 3A4 are the major enzymes that catalyze antidepressant metabolic reactions. Antidepressants can be either substrates or inhibitors of these enzymes, which also metabolize many other pharmacologic agents. Although the cytochrome enzymes that metabolize antidepressants have not been fully characterized, interaction profiles of the newer antidepressants are becoming more clearly defined. Determining patient phenotypes is not practical in the clinical setting, but an awareness of the possibility of genetic polymorphism in antidepressant metabolism may help explain therapeutic failure or toxicity, help predict the likelihood of drug interactions, and help clinicians better manage antidepressant drug therapy.

Genetic Variation: Impact on Folate (and Choline) Bioefficacy

2010 ◽  
Vol 80 (45) ◽  
pp. 319-329 ◽  
Author(s):  
Allyson A. West ◽  
Marie A. Caudill
Keyword(s):  
Carbon Metabolism ◽  
Genetic Variants ◽  
Plasma Homocysteine ◽  
Water Soluble ◽  
Gene Interactions ◽  
Dietary Folate ◽  
Methyl Donors ◽  
Common Genetic Variants ◽  
One Carbon Metabolism ◽  
The Impact

Folate and choline are water-soluble micronutrients that serve as methyl donors in the conversion of homocysteine to methionine. Inadequacy of these nutrients can disturb one-carbon metabolism as evidenced by alterations in circulating folate and/or plasma homocysteine. Among common genetic variants that reside in genes regulating folate absorptive and metabolic processes, homozygosity for the MTHFR 677C > T variant has consistently been shown to have robust effects on status markers. This paper will review the impact of genetic variants in folate-metabolizing genes on folate and choline bioefficacy. Nutrient-gene and gene-gene interactions will be considered along with the need to account for these genetic variants when updating dietary folate and choline recommendations.

Bleeding Classification in Clinical Trials: Observer Variability and Clinical Relevance

1997 ◽  
Vol 78 (04) ◽  
pp. 1189-1192 ◽  
Author(s):  
Yvonne P Graafsma ◽  
Martin H Prins ◽  
Anthonie W A Lensing ◽  
Rob J de Haan ◽  
Menno V Huisman ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Clinical Relevance ◽  
Area Under The Curve ◽  
Weighted Kappa ◽  
Clinical Severity ◽  
Minor Bleeding ◽  
Recent Trial ◽  
Bleeding Episodes ◽  
The Impact ◽  
Adjudication Committee

SummaryTo evaluate the bleeding classification in a recent trial on venous thrombosis treatment, a selection of reported bleeding episodes was adjudicated twice by an independent committee and graded by the treating physician and independent clinical experts on the clinical severity and impact on the patient’s life.The kappa values for the dichotomy major bleeding versus minor or no bleeding were 0.79 (95% CI, 0.57-1.0) for the agreement between the two members of the adjudication committee and 0.77 (95% CI, 0.52-1.0) for the agreement between both adjudication sessions. The kappa values for the dichotomy major or minor bleeding versus no bleeding were 0.42 and 0.44. The weighted kappa values for the agreement between the treating physician and the independent experts were 0.76 for the Clinical severity and 0.79 for the impact on the patient’s life (95% CI, 0.63-0.88 and 0.70-0.89). The association between the adjudication result expressed as major bleeding or minor or no bleeding and the Clinical grading by the treating physician resulted in an ROC curve with an area under the curve of 0.98 for the Clinical severity and 0.99 for the impact on the patient’s life. The dichotomy major or minor bleeding versus no bleeding resulted in areas under the curve of 0.70 and 0.66.In conCIusion, the applied criteria for major bleeding are reproducible and Clinically relevant. The criteria for minor bleeding are not reproducible and are less associated with the observed Clinical relevance.

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