of this water-soluble byproduct. As such, SCr is a variable used in several calculations employed to characterize renal function. However, given that declines in muscle mass generally accompany advancing age, it is possible that an elderly patient’s low to normal SCr may yield a false assumption of preserved kidney function. The Cockcroft–Gault equation, first published in 1976, applies the variables of age, weight, gender, and SCr to estimate creatinine clearance (CrCl), which remains the most used estimate of renal function for drug dosing (Cockcroft & Gault, 1976). Since SCr appears in the denominator of this equation, elderly patients with low muscle mass and corresponding SCr values less than 1 mg/dL may have a calculated CrCl substantially higher than would be expected. Some clinicians have used a SCr value of 1 mg/dL when estimating CrCl in an elderly patient with an actual SCr value less than 1 mg/dL, which may mitigate overestimates of renal function. However, there are conflicting opinions on the merits of this approach (Nguyen et al., 2018). The Modification of Diet in Renal Disease (MDRD) equation was developed as a tool to estimate glomerular filtration rate (eGFR), largely for the purpose of assigning a patient’s stage of chronic kidney disease (Levey et al., 1999). However, it was recognized that using the MDRD equation’s eGFR to make drug dosing adjustments had limitations (Probst et al., 2008). The CKD-EPI equation was proposed as an improved version of the MDRD equation (Levey Pharmacodynamics Once a medication reaches its site of action, the effects of that medication on a person or organ system (pharmacodynamics) may vary among individuals and elicit intraindividual variation due to coexisting or confounding patient factors. Older patients with acute illness and/or advancing chronic conditions may be more sensitive to medications’ clinical and adverse effects. This may present as orthostasis associated with antihypertensive therapy, confusion from anticholinergic drugs, or imbalance from sedatives or opioids. Frailty, a condition associated with reduced physiologic reserves and impaired ability to respond to stressors, is often ascribed to older adults. While physiologic Pharmacogenomics Inherited genetic traits are known to influence individual physical characteristics and predisposition to disease. Literature now provides robust evidence that an individual’s genetic traits impact their response to medications, and this principle is called pharmacogenomics (PGx). Such altered responses may encompass extremes of drug-metabolizing enzyme activity and predisposition to medication side effects, which may range from treatment failure to toxicity. Testing for PGx variants may be accomplished by laboratory analysis of one or, more preferably, a panel of genes from a simple cheek swab. The results of these tests can then be applied to current and future lifelong medication treatment decisions. While PGx can be impactful to medication management in patients of all ages, increased polypharmacy and multiple comorbidities increase the likelihood that an elderly patient may benefit as much as, if not more than, a younger patient. Highlighted facts pertaining to pharmacogenomics and adverse medication outcomes include: ● Evidence-based PGx guidelines exist for hundreds of medications, including approximately 20% of the top 100 selling medications in the U.S.
et al., 2009). However, elderly patients were underrepresented among study subjects, and limitations of applying the equation to patients with low serum creatinine were acknowledged. Given that most drug-dosing guidelines were established with reference to creatinine clearance, the Cockcroft–Gault equation remains the generally preferred method of drug-dosing decision making. Other factors negatively impact renal function, including hypertension, diabetes mellitus, glomerulonephritis, and medications with direct or indirect nephrotoxic effects. Self-Assessment Quiz Question #3 Which statement reflects a sound rationale for making medication selection decisions based on pharmacologic factors? a. It avoids the need to watch TV commercials for newly marketed medications. b. Patient-specific factors, safety concerns, or drug interactions may make one medication class preferable to another. c. It is okay to use any medication if the indication for use matches the package insert. d. All options within a given class of medications have the same benefit/effect on all patients. changes can impart pharmacokinetic changes, frailty can predispose patients to altered pharmacodynamic responses to medications (Maher et al., 2020). Drug–drug interactions may also present as pharmacodynamic problems, such as serotonin syndrome and anticholinergic syndrome. Therefore, given the decline in certain physiologic functions and the direct correlation between advancing age and the average number of medications prescribed to treat a growing number of medical conditions, it is reasonable to expect that aging adults have a higher likelihood of experiencing adverse drug reactions than their younger counterparts receiving the same treatment for similar conditions. ● Adverse drug events were recognized as the fourth leading cause of death in U.S. patients. ● Nonoptimized medication use has been associated with over $528 billion in avoidable medical spending; 1.2 million unplanned ER visits; and 275,000 deaths each year. Expert opinion and a growing body of evidence support that comprehensive medication reviews, including PGx testing, can favorably influence patient outcomes, including reducing healthcare costs and increasing patient and provider experience while reducing the “trial and error” approach to medication selection (Get the Medications Right Institute, 2022). A full discussion of the value of pharmacogenomics is beyond the scope of this course; however, healthcare providers should be aware that individual genetic traits may affect patient responses to, and outcomes related to medications used to treat numerous conditions, including stroke, myocardial infarction, depression and other mental health conditions, cancer, gastrointestinal disorders, and musculoskeletal conditions.
HEALTHCARE DISORDERS THAT INFLUENCE MEDICATION RESPONSES
Diabetes mellitus As the incidence of diabetes mellitus in the U.S. population continues to increase, so does the incidence of associated complications. Poorly controlled diabetes is known to have negative macrovascular and microvascular effects, including diabetic nephropathy attributable to persistent proteinuria and a progressive decline in renal function. Therefore, older patients
with a longstanding history of diabetes mellitus are likely to have worse renal function than nondiabetic patients of a similar age. As described above, the altered renal function not appropriately accounted for in the selection and dosing of renally eliminated medications can increase the likelihood and/or severity of adverse drug effects. Additionally, the physiologic changes
EliteLearning.com/Pharmacy-Technician
Book Code: RPTTX2024
Page 79
Powered by FlippingBook