<i>Primun Non Nocere</i>
            , Polypharmacy and Pharmacogenetics

Isidoro‐García, María; Sánchez-Martín, Almudena; García‐Berrocal, Belén; Román-Curto, Concépción

doi:10.2217/pgs.15.137

Cited by 11 publications

(8 citation statements)

References 4 publications

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“…A recent article reviewed a case of a 74-year-old woman with polypharmacy hospitalized due to severe ADE. 43 Pharma-cogenetic testing in this patient established major genetic CYP3A5 polymorphism. Ensuing pharmacogenetic-guided medication regimen readjustment led to remarkable patient recovery with complete remission of coetaneous symptoms and control of cardiac, hepatic, and renal symptomatology.…”

Section: Discussionmentioning

confidence: 83%

“… 19 Additionally, this new technology can lead to a decrease in the number of ADEs and the enormous costs associated with these iatrogenic hospitalizations and emergency room visits. 43 Recent reports demonstrated that there is a significant overlap between classes of medications most frequently implicated as cause of ADE in older adults 36 , 44 and classes of medications, action of which is significantly affected by pharmacogenetic polymorphisms. 10 These classes include anticoagulants, β-blockers, calcium-channel blockers, nonsteroidal anti-inflammatory drugs, antibiotics, antidepressants, benzodiazepines, proton pump inhibitors, and chemotherapeutic agents.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacogenetic polymorphism as an independent risk factor for frequent hospitalizations in older adults with polypharmacy: a pilot study

Finkelstein¹,

Friedman²,

Hripcsak³

et al. 2016

PGPM

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Pharmacogenetic testing identifies genetic biomarkers that are predictive of individual sensitivity to particular drugs. A significant proportion of medications that are widely prescribed for older adults are metabolized by enzymes that are encoded by highly polymorphic genes. Pharmacogenetic testing is increasingly used to optimize the medication regimen; however, its potential in older adults with polypharmacy has not been systematically explored. Following the initial case–series study, this study hypothesized that frequently hospitalized older adults with polypharmacy have higher frequency of pharmacogenetic polymorphism as compared to older adults with polypharmacy who are rarely admitted to a hospital. To test this hypothesis, a nested case–control study was conducted with pharmacogenetic polymorphism as an exposure and hospitalization rate as an outcome. In this study, frequently hospitalized older adults (≥65 years of age) with polypharmacy were matched with rarely hospitalized older adults with poly-pharmacy by age, gender, race, ethnicity, and chronic disease score. Average age and number of prescription drugs did not differ in cases and controls (77.2±5.0 and 78.3±5.1 years, 14.3±5.3 and 14.0±2.9 medications, respectively). No statistically significant difference in sociodemographic, clinical, and behavioral characteristics that are known to affect hospitalization risk was found between the cases and controls. Major pharmacogenetic polymorphism defined as presence of at least one allelic combination resulting in poor or rapid metabolizer status was identified in all the cases. No major pharmacogenetic polymorphisms were detected in controls. Based on the exact McNemar’s test, the difference in major pharmacogenetic polymorphism frequency between cases and controls was statistically significant (p<0.05). In 50% of cases, more than one major pharmacogenetic polymorphism was found. The frequency of CYP2C19 rapid metabolizer, CYP3A4/5 poor metabolizer, VKORC1 low sensitivity, and CYP2D6 rapid metabolizer status in cases was 67%, 33%, 33%, and 17%, respectively, which significantly exceeded respective prevalence in general population. The mean number of major gene–drug interactions found in cases was 2.8±2.2, whereas no major drug–gene interactions were identified in controls. The difference in the number of major drug–gene interactions between cases and controls was statistically significant (p<0.05). The pilot data supported the hypothesis that pharmacogenetic polymorphism may represent an independent risk factor for frequent hospitalizations in older adults with polypharmacy. Due to small sample size, the results of this proof-of-concept study cannot be conclusive. Further work on the utility of pharmacogenetic testing for optimization of medication regimens in this vulnerable group of older adults is warranted.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Pharmacogenetic polymorphism as an independent risk factor for frequent hospitalizations in older adults with polypharmacy: a pilot study

Finkelstein¹,

Friedman²,

Hripcsak³

et al. 2016

PGPM

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“… 36 The results of this study showed that patients treated according to pharmacogenomics-guided treatment plan had a significant decrease in hospitalizations and emergency department visits with average cost savings in the amount of US$218. In an interesting instructive case presented by Isidoro-García et al, 37 a 74-year-old woman with multiple comorbidities and polypharmacy developed erythrodermic psoriasis on admission to a cardiology department with CHF, atrial fibrillation, and chronic renal failure. A personalized PGx analysis found that this patient was homozygous for CYP3A5*3 and heterozygous for 3435C>T MDR1.…”

Section: Discussionmentioning

confidence: 99%

Potential utility of precision medicine for older adults with polypharmacy: a case series study

Finkelstein¹,

Friedman²,

Hripcsak³

et al. 2016

PGPM

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Pharmacogenomic (PGx) testing has been increasingly used to optimize drug regimens; however, its potential in older adults with polypharmacy has not been systematically studied. In this hypothesis-generating study, we employed a case series design to explore potential utility of PGx testing in older adults with polypharmacy and to highlight barriers in implementing this methodology in routine clinical practice. Three patients with concurrent chronic heart and lung disease aged 74, 78, and 83 years and whose medication regimen comprised 26, 17, and 18 drugs, correspondingly, served as cases for this study. PGx testing identified major genetic polymorphisms in the first two cases. The first case was identified as “CYP3A4/CYP3A5 poor metabolizer”, which affected metabolism of eleven prescribed drugs. The second case had “CYP2D6 rapid metabolizer” status affecting three prescribed medications, two of which were key drugs for managing this patient’s chronic conditions. Both these patients also had VKORC1 allele *A, resulting in higher sensitivity to warfarin. All cases demonstrated a significant number of potential drug–drug interactions. Both patients with significant drug–gene interactions had a history of frequent hospitalizations (six and 23, respectively), whereas the person without impaired cytochrome P450 enzyme activity had only two acute episodes in the last 5 years, although he was older and had multiple comorbidities. Since all patients received guideline-concordant therapy from the same providers and were adherent to their drug regimen, we hypothesized that genetic polymorphism may represent an additional risk factor for higher hospitalization rates in older adults with polypharmacy. However, evidence to support or reject this hypothesis is yet to be established. Studies evaluating clinical impact of PGx testing in older adults with polypharmacy are warranted. For practical implementation of pharmacogenomics in routine clinical care, besides providing convincing evidence of its clinical effectiveness, multiple barriers must be addressed. Introduction of intelligent clinical decision support in electronic medical record systems is required to address complexities of simultaneous drug–gene and drug–drug interactions in older adults with polypharmacy. Physician training, clear clinical pathways, evidence-based guidelines, and patient education materials are necessary for unlocking full potential of pharmacogenomics into routine clinical care of older adults.

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“…Polypharmacy is a term used to describe the situation in which a patient is taking five or more drugs [1]. It often occurs among elderly people and is associated with an increased risk of drug-drug interactions (DDIs), which impact on patient health, effectiveness of drugs, and increased medical costs [2].…”

Section: Introductionmentioning

confidence: 99%

“…Drug metabolism via the cytochrome P450 (CYP) system has emerged as an important determinant in the incidence of several DDIs that can result in drug toxicities, reduced pharmacological effect, and adverse drug reactions [2,3,4].…”

Section: Introductionmentioning

confidence: 99%

Physical Performance and Quality of Life in Older Adults: Is There Any Association between Them and Potential Drug Interactions in Polymedicated Octogenarians?

Verde

Diego

Chicharro

et al. 2019

IJERPH

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Older adults are at increased risk of several cytochrome P450 (CYP) drug interactions that can result in drug toxicity, reduced pharmacological effect, and adverse drug reactions. This study aimed to assess the prevalence of potential CYP interactions referring to the most clinically relevant drugs and exploring the relationship between them and quality of life and physical performance in Spanish octogenarians. Institutionalized and community-dwelling octogenarians (n = 102) treated at three primary care centers, were recruited by a research nurse. Anthropometric measurements, chronic diseases, prescribed drugs, quality of life, physical performance, mobility skills, hand grip strength and cognitive status data were collected. Potential CYP drug-drug interactions (DDIs) were selected referring to the main CYP implicated in their metabolism. The 72.2% of recruited octogenarians presented potentially inappropriate CYP inhibitor-substrate or CYP inductor-substrate combinations. Analyzing the EuroQol Visual Analogue scale (EQ-VAS) results, patients with a potential CYP DDI perceived worse health status than patients without it (p = 0.004). In addition, patients with a potential CYP DDI presented worse exercise capacity, kinesthetic abilities, or mobility than those who didn’t present a potential interaction (p = 0.01, p = 0.047, and p = 0.02, respectively). To investigate and control factors associated with loss of muscle strength and poor quality of life, polypharmacy and DDIs could help institutions in the management of physical frailty.

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Primun Non Nocere , Polypharmacy and Pharmacogenetics

Cited by 11 publications

References 4 publications

Pharmacogenetic polymorphism as an independent risk factor for frequent hospitalizations in older adults with polypharmacy: a pilot study

Pharmacogenetic polymorphism as an independent risk factor for frequent hospitalizations in older adults with polypharmacy: a pilot study

Potential utility of precision medicine for older adults with polypharmacy: a case series study

Physical Performance and Quality of Life in Older Adults: Is There Any Association between Them and Potential Drug Interactions in Polymedicated Octogenarians?

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