CYP2D6*4, CYP3A5*3 and ABCB1 3435T polymorphisms and drug-related falls in elderly people

Blonk, Maren I.; Velde, Nathalie van der; Bemt, Patricia M. L. A. van den; Schaik, Ron H.N. van; Cammen, Tischa J. M. van der

doi:10.1007/s11096-009-9349-1

Cited by 11 publications

(10 citation statements)

References 11 publications

(13 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A similar result was observed in the P-gp subgroup (3435TT versus 3435CC + 3435CT), with an OR of 2.1 (95% CI 0.2–17.2). For users of CYP3A5 substrates, there appeared to be no difference in fall risk between PMs (n=49) and EMs + IMs (n=14) (OR 0.9, 95% CI 0.2–3.3) 28. The lack of statistical significance of the increased OR seen in the CYP2D6 and P-gp subgroup might be due to the fact that the cohorts were insufficiently powered for the subanalysis.…”

Section: Resultsmentioning

confidence: 93%

Effects of drug pharmacokinetic/pharmacodynamic properties, characteristics of medication use, and relevant pharmacological interventions on fall risk in elderly patients

Chen¹,

Zhu²,

Zhou³

2014

TCRM

View full text Add to dashboard Cite

BackgroundFalls among the elderly are an issue internationally and a public health problem that brings substantial economic and quality-of-life burdens to individuals and society. Falls prevention is an important measure of nursing quality and patient safety. Numerous studies have evaluated the association of medication use with fall risk in elderly patients. However, an up-to-date review has not been available to summarize the multifaceted pharmaceutical concerns in the prevention of medication-related falls.Materials and methodsRelevant literature was identified by performing searches in PubMed, Web of Science, and the Cochrane Library, covering the period until February 2014. We included studies that described an association between medications and falls, and effects of drug pharmacokinetic/pharmacodynamic properties, characteristics of medication use, and pharmacological interventions on fall risk in elderly patients. The full text of each included article was critically reviewed, and data interpretation was performed.ResultsFall-risk-increasing drugs (FRIDs) include central nervous system-acting agents, cough preparations, nonsteroidal anti-inflammatory drugs, anti-Alzheimer’s agents, antiplatelet agents, calcium antagonists, diuretics, α-blockers, digoxin, hypoglycemic drugs, neurotoxic chemotherapeutic agents, nasal preparations, and antiglaucoma ophthalmic preparations. The degree of medication-related fall risk was dependent on one or some of the following factors: drug pharmacokinetic/pharmacodynamic properties (eg, elimination half-life, metabolic pathway, genetic polymorphism, risk rating of medications despite belonging to the same therapeutic class) and/or characteristics of medication use (eg, number of medications and drug–drug interactions, dose strength, duration of medication use and time since stopping, medication change, prescribing appropriateness, and medication adherence). Pharmacological interventions, including withdrawal of FRIDs, pharmacist-conducted clinical medication review, and computerized drug alerts, were effective in reducing fall risk.ConclusionBased on the literature review, clear practical recommendations for clinicians to prevent falls in the elderly included making a list of FRIDs, establishing a computerized alert system for when to e-prescribe FRIDs, seeking an alternative drug with lower fall risk, withdrawing FRIDs if clinically indicated, taking pertinent cautions when the use of FRIDs cannot be avoidable, paying attention to prescribing appropriateness, simplifying the medication regimen, strengthening pharmacist-conducted clinical medication review, ensuring the label of each FRID dispensed contains a corresponding warning sign, being careful when medication change occurs, enhancing medication adherence, and mandating for periodic reassessment of potential risk associated with the patient’s medication regimen. Further studies should be conducted in this area, such as investigating whether medication reconciliation and improving medication adherence could decrease th...

show abstract

Section: Resultsmentioning

confidence: 93%

Effects of drug pharmacokinetic/pharmacodynamic properties, characteristics of medication use, and relevant pharmacological interventions on fall risk in elderly patients

Chen¹,

Zhu²,

Zhou³

2014

TCRM

View full text Add to dashboard Cite

show abstract

“…Panagiotidis et al 73 also investigated that no correlation between the number of CYP2D6 alleles and side effects exists. Blonk et al 74 have also observed no significant CYP2D6*2 allele with drug-related falls in elderly people. In a recent study, Tiwari et al 75 also showed no significant association between CYP2D6*2 with tradative dyskinesia (P 5 0.935) in North Indian patients with chronic Schizophrenia.…”

Section: Discussionmentioning

confidence: 94%

CYP2D6*2 Polymorphism as a Predictor of Failed Outpatient Tramadol Therapy in Postherpetic Neuralgia Patients

Nasare

Banerjee

Deshmukh

et al. 2016

American Journal of Therapeutics

View full text Add to dashboard Cite

Human cytochrome P4502D6 (CYP2D6) gene is highly polymorphic, leading to wide interindividual ethnic differences in CYP2D6-mediated drug metabolism. Its activity ranges from complete deficiency to excessive activity, potentially causing toxicity of the medication or therapeutic failure with recommended drug dosages. The aim of the study was to find the association of CYP2D6*2 polymorphisms with demographic characters (age, sex, and weight), pain intensity scales [numerical rating scale (NRS) sleep, global perceived effect (GPE)], and adverse drug effects in postherpetic neuralgia (PHN) patients receiving tramadol. The study comprised 246 patients [including 123 nonresponders (NRs) and 123 responders (Rs)] with PHN undergoing analgesic treatment at the pain clinic, Out Patient Department, University College of Medical Sciences, Guru Teg Bahadur Hospital, Delhi, India. Patients with any history of diabetes mellitus, human immunodeficiency virus, malignancy, hematological or liver disease, psychiatric illness, alcohol abuse, and tramadol sensitivity were excluded from the study. The NRSs of (resting and movement), NRS-sleep, and GPE were evaluated by the treating physician. Adverse drug effects during the time of the study were recorded. All samples were analyzed for CYP2D6*2 polymorphism using the polymerase chain reaction-restriction fragment length polymorphism method. The genotype distribution did not vary significantly among genders [NR (P = 0.723); R (P = 0.947)] and different age groups in NRs (P = 0.763) and Rs (P = 0.268). Clinically, statistically significant (P < 0.001) results were obtained in both the groups when compared with baseline in the NRS-sleep and GPE scores, whereas no association was found between NRS-sleep and GPE scores when compared with CYP2D6*2 genotype (P > 0.05). In addition, CYP2D6*2 genotype was not related to the adverse effects of analgesic therapy. The overall results suggested that CYP2D6*2 polymorphism plays no role in the PHN patients receiving tramadol treatment. The CYP2D6*2 polymorphism may not be a predictor of treatment outcome of patients with respect to PHN-receiving tramadol.

show abstract

“…For users of CYP3A5 substrates, there appeared to be no difference in fall risk between PMs (n=49) and EMs + IMs (n=14) (OR 0.9, 95% CI 0.2-3.3). 28 The lack of statistical significance of the increased OR seen in the CYP2D6 and P-gp subgroup might be due to the fact that the cohorts were insufficiently powered for the subanalysis. It is worth conducting a prospective study in a larger population to confirm the possible association of genetic polymorphism with fall risk in the elderly.…”

Section: Genetic Polymorphismmentioning

confidence: 99%

Effects of drug pharmacokinetic/pharmacodynamic properties, characteristics of medication use, and relevant pharmacological interventions on fall risk in elderly patients

Zhou¹,

Chen²,

Zhu³

2014

OTT

View full text Add to dashboard Cite

Background: Falls among the elderly are an issue internationally and a public health problem that brings substantial economic and quality-of-life burdens to individuals and society. Falls prevention is an important measure of nursing quality and patient safety. Numerous studies have evaluated the association of medication use with fall risk in elderly patients. However, an upto-date review has not been available to summarize the multifaceted pharmaceutical concerns in the prevention of medication-related falls. Materials and methods: Relevant literature was identified by performing searches in PubMed, Web of Science, and the Cochrane Library, covering the period until February 2014. We included studies that described an association between medications and falls, and effects of drug pharmacokinetic/pharmacodynamic properties, characteristics of medication use, and pharmacological interventions on fall risk in elderly patients. The full text of each included article was critically reviewed, and data interpretation was performed. Results: Fall-risk-increasing drugs (FRIDs) include central nervous system-acting agents, cough preparations, nonsteroidal anti-inflammatory drugs, anti-Alzheimer's agents, antiplatelet agents, calcium antagonists, diuretics, α-blockers, digoxin, hypoglycemic drugs, neurotoxic chemotherapeutic agents, nasal preparations, and antiglaucoma ophthalmic preparations. The degree of medication-related fall risk was dependent on one or some of the following factors: drug pharmacokinetic/pharmacodynamic properties (eg, elimination half-life, metabolic pathway, genetic polymorphism, risk rating of medications despite belonging to the same therapeutic class) and/or characteristics of medication use (eg, number of medications and drug-drug interactions, dose strength, duration of medication use and time since stopping, medication change, prescribing appropriateness, and medication adherence). Pharmacological interventions, including withdrawal of FRIDs, pharmacist-conducted clinical medication review, and computerized drug alerts, were effective in reducing fall risk. Conclusion: Based on the literature review, clear practical recommendations for clinicians to prevent falls in the elderly included making a list of FRIDs, establishing a computerized alert system for when to e-prescribe FRIDs, seeking an alternative drug with lower fall risk, withdrawing FRIDs if clinically indicated, taking pertinent cautions when the use of FRIDs cannot be avoidable, paying attention to prescribing appropriateness, simplifying the medication regimen, strengthening pharmacist-conducted clinical medication review, ensuring the label of each FRID dispensed contains a corresponding warning sign, being careful when medication change occurs, enhancing medication adherence, and mandating for periodic reassessment of potential risk associated with the patient's medication regimen. Further studies should be conducted in this area, such as investigating whether medication reconciliation and improving medication adherence could ...

show abstract

CYP2D64, CYP3A53 and ABCB1 3435T polymorphisms and drug-related falls in elderly people

Abstract: The hypothesis that 'poor metabolizers' have an increased fall risk was not confirmed. A larger study population is needed to confirm the potential association that was seen between CYP2D6*4 and ABCB1 3435T polymorphisms and drug-related falls.

Cited by 11 publications

References 11 publications

Effects of drug pharmacokinetic/pharmacodynamic properties, characteristics of medication use, and relevant pharmacological interventions on fall risk in elderly patients

Effects of drug pharmacokinetic/pharmacodynamic properties, characteristics of medication use, and relevant pharmacological interventions on fall risk in elderly patients

CYP2D6*2 Polymorphism as a Predictor of Failed Outpatient Tramadol Therapy in Postherpetic Neuralgia Patients

Effects of drug pharmacokinetic/pharmacodynamic properties, characteristics of medication use, and relevant pharmacological interventions on fall risk in elderly patients

Contact Info

Product

Resources

About