Improving the Care of Older Patients by Decreasing Potentially Inappropriate Medications, Potential Medication Omissions, and Serious Drug Events Using Pharmacogenomic Data about Variability in Metabolizing Many Medications by Seniors.

Roger E Thomas

doi:10.3390/geriatrics5040064

Abstract

Polypharmacy, potentially inappropriate medications (PIMs) identified by the American Geriatrics Society and Screening Tool of Older People’s Prescriptions (STOPP), potential prescribing omissions (PPOs) identified by Screening Tool to Alert to Right Treatment (START) and serious drug events (SDEs), are major problems for seniors. They correlate with increased risks of rehospitalization and death within six months of hospital discharge. About 75% of commonly prescribed medications are metabolized by P450 cytochrome enzymes. Electronic medical records (EMRs) providing integrated comprehensive pharmacogenomic advice are available only in very large health organizations. The study design of this article is a cross-sectional analysis of the American Geriatrics Society (AGS) and STOPP PIM and START PPO databases integrated with three P450 cytochrome enzyme databases (Flockhart Tables, DrugBank, and Rx Files) and the data are reported using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: guidelines for reporting observational studies. To enable optimally prudent prescribing this article presents for primary care physicians and physicians in remote or rural areas without access to such services a comprehensive integration of the data on PIM and PPO medications with the data on the P450 cytochrome isoforms that metabolize these medications. Additionally presented are the medications metabolized by multiple isoforms and medications that inhibit or induce individual or multiple isoforms. The most extensive metabolic activities involve the central nervous system, anxiolytic, antidepressive, antipsychotic, musculoskeletal, and cardiovascular drugs. The P450 cytochrome isoforms that metabolize the most medications are 3A457, 2C9, 2D6, and 2C19 and nearly all central nervous systems medications compete to be metabolized by 3A457. Medications with the largest inducer or inhibitor activity are highlighted and also a list of commonly prescribed medications that are neither PIMs nor PPOs but compete for metabolism by the same isoforms.

Highlights

The 2017 Global Burden of Disease Study 2017 found that the number of people ≥65 years increased globally by 105% from 327.6 million in 1990 to 673.7 million in 2017 with the highest proportional increases in high-income countries from 121.5 million (12.1% of the population) to 208.6 million (17.5% of the population)
Screening Tool of Older People’s Prescriptions (STOPP) potentially inappropriate medications (PIMs) and Screening Tool to Alert to Right Treatment (START) potential prescribing omissions (PPOs) databases integrated with three P450 cytochrome enzyme databases (Flockhart Tables, DrugBank, and Rx Files) and the data are reported using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: guidelines for reporting observational studies
The first is the American Geriatric Society criteria [4] and the Screening Tool of Older People’s Prescriptions (STOPP)/Screening Tool to Alert to Right Treatment (START) [5] criteria, which are based on systematic literature reviews evaluated by geriatric experts

Summary

Introduction

The 2017 Global Burden of Disease Study 2017 found that the number of people ≥65 years increased globally by 105% from 327.6 million in 1990 to 673.7 million in 2017 with the highest proportional increases in high-income countries from 121.5 million (12.1% of the population) to 208.6 million (17.5% of the population). The global number of deaths increased from 19.1 million to 32.2 million. The top 10 causes of death for both sexes were ischemic heart disease, stroke, Alzheimer and other. The demands for health care and especially for seniors are increasing, with corresponding increases in budgets and numbers of medications. A key question is whether prescribing for seniors is optimally evidence-based. There are two key sources for this evidence base. The first is the American Geriatric Society criteria [4] and the Screening Tool of Older People’s Prescriptions (STOPP)/Screening Tool to Alert to Right Treatment (START) [5] criteria, which are based on systematic literature reviews evaluated by geriatric experts

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Conclusion