have indicated its effectiveness as better than placebo and as effective as some standard antidepressants for mild to moderate depression. Additionally, significant drug interactions between St. John’s wort and numerous other medications exist due to their apparent impact on the drug-metabolizing enzyme CYP3A4 and the transporter p-glycoprotein. This information supports the notion that while it is considered a supplement sourced from natural products, its safety and efficacy concerns are no less than for prescription medications. Other plant-derived substances are the source of highly effective yet potentially toxic prescription medications, such as digoxin and vincristine. Digoxin has been a mainstay in treating heart failure and certain cardiac arrhythmias for decades. Its earliest documented use was in 1785 by Sir William Withering, who employed the foxglove plant Digitalis purpurea to treat edematous states and heart failure. However, it may have been used as a cardiotonic for centuries prior (Eichhorn & Gheorghiade, 2002). While contemporary pharmaceutical manufacturing methods may now allow for synthetic production, extracts from Digitalis lanata are still used as source material for pharmaceutical-grade digoxin. The side effects and, at certain concentrations, toxicities of digoxin are well established and include visual disturbances, vomiting, delirium, bradycardia, and other arrhythmias. Digoxin has a narrow therapeutic range, with serum levels measured in nanograms per deciliter concentrations, and signs of toxicity often presenting at or even in the range of concentrations previously considered clinically effective (Hauptman et al., 2013). Alcohol use Chronic alcohol use has been associated with the development of impaired hepatic function, which may lead to portal hypertension, ascites, and/or esophageal varices. With advancing hepatic disease, the liver’s impaired production of coagulation factors such as vitamin K may negatively affect the response to medications such as warfarin. Patients with Child- Pugh B and C classifications may have a hepatic impairment,
Several medications employed as chemotherapy for several oncologic conditions are also derivatives of plant sources. Vincristine, originally isolated from the vinca plant, is a potent agent that remains the backbone of treatment for acute lymphoblastic leukemia and has utility in a variety of other cancer therapies. Its pharmacologic effect is associated with disrupting microtubules, which interrupts cell proliferation. However, gastrointestinal and severe neurologic toxicities have been associated with its use, including near-certain fatality if it is administered intrathecally. Bark from the Pacific yew tree was the original source of the chemotherapy agent taxol, studies of which began in 1962 and ultimately led to FDA approval in 1992 (National Cancer Institute, n.d.). Initially indicated in the treatment of ovarian cancer, its effectiveness has since been demonstrated in breast and several other cancers. While pharmaceutical manufacturing advances now allow for the synthetic production of taxol and its derivatives, early production of and treatment with taxol relied on material from its natural plant source. Like many other chemotherapy agents, taxol has a range of neurologic, hematologic, and hypersensitivity- associated toxicities above and sometimes within usual doses or treatment durations. Other examples exist of naturally sourced or derived pharmaceutical-grade medications and complementary therapies. However, as the above examples depict, natural does not reliably mean safe, whether from an effect, interaction, or toxicity perspective! which could add concern for or preclude the use of certain medications that depend on drug metabolizing enzymes for safe biotransformation. Additionally, the central nervous system depressant effects of alcohol ingestion could be additive or synergistic to medications active in the central nervous system (CNS), including sedatives, anxiolytics, antidepressants, analgesics, and antiepileptics.
COMMON MEDICATION ISSUES IN OLDER ADULTS
Polypharmacy Polypharmacy is generally defined as a condition in which patients take five or more chronic medications. Others have proposed that polypharmacy can simply be defined as the presence of unnecessary drug therapy or that which may do more harm than good (Wooten, 2015a). The scope of this problem is extensive, given that 40% of older adults take more than five scheduled medications regularly. Further, a logical, direct correlation exists between an increasing number of prescribed medications and the risk of exposure to potentially inappropriate medications (Weng et al., 2013). Polypharmacy has a broad range of negative implications, including increased incidence of adverse effects; increased likeliness of medication noncompliance; increased utilization of healthcare resources, including hospitalization; higher healthcare costs; and elevated mortality risks (Gutierrez-Valencia et al., 2017). Hyperpolypharmacy, defined as the regular use of 10 or more medications, has been associated with an even greater incidence of adverse effects, hospitalizations, and developing Inappropriate prescribing Inappropriate prescribing may involve ordering more medications than are clinically necessary (overprescribing), incorrectly prescribing a medication for a clinically necessary Potentially inappropriate medications As defined in the Beers criteria (Beers et al., 1991; 2019 AGS Beers Criteria Update Expert Panel, 2019; 2023 AGS Beers Criteria Update Expert Panel, 2023), PIMs include those medications that are known to confer higher risks for adverse outcomes in geriatric patients, are contraindicated in the presence of other medications or conditions or would require
frailty (Gnjidic et al., 2012). Similarly, in a systematic review, Toh and colleagues identified that polypharmacy existed in a pooled average of 59% of patients with frailty; hyperpolypharmacy was present in 22% of patients with frailty (Toh et al., 2023). Bosch- Lender and colleagues (2016) identified that polypharmacy in adults older than age 80 was associated with a reduction in patient knowledge of each prescribed medication’s indication for use. This knowledge impediment was offset if a patient had independent living arrangements with a partner. Concomitant use of increasing numbers of medications also yields a corresponding increase in the likelihood of drug– drug interactions. Such interactions can affect the absorption, distribution, metabolism, or excretion of one or more medications, resulting in altered pharmacokinetic responses. Additionally, by virtue of interactions or combined effects, drug combinations have been associated with increased falls, hospitalizations, and risk of death (Wooten, 2015a; Toh et al., 2023).
condition (misprescribing), and/or failing to prescribe a medication for a clinically valid condition (Thevelin et al., 2019).
therapy adjustment based on age-related pharmacokinetic or pharmacodynamic changes. Key among the potentially inappropriate medications (PIMs) are those drugs associated with altered sensorium and increased risk of falls, including sedatives and those with anticholinergic properties.
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