Pharmacokinetics and Pharmacodynamics

Knowledge of the physiologic changes that occur with aging is essential when prescribing medications to the elderly patient. Changes in pharmacokinetics and pharmacodynam-ics can result in increased or decreased amounts of medication and drug-drug interactions (Table 4-11).

Pharmacokinetics refers to the body's response to the drug and includes absorption, distribution, metabolism, and elimination (excretion). Age-related gastrointestinal and skin changes have minimal effect on drug absorption, except for drugs that require active gastrointestinal transport (vitamins, minerals), which decreases with aging. The volume of distribution (Vd) is determined by degree of plasma protein binding and body composition. The changes in protein binding are not clinically significant, unless a condition (e.g., acute illness, malnutrition) is causing a marked decline in albumin. Water composition and lean body mass decrease with aging. Fat composition increases, resulting in a larger Vd of lipid-soluble drugs, such as benzodiazepines. Although liver function tests are unchanged, liver size and blood flow are somewhat reduced. The clinical significance is difficult to determine because there is such wide interindividual variation in hepatic metabolism. Drug elimination is mainly affected by a decrease in creatinine clearance. Also, decreased muscle mass causes a decrease in serum creatinine. Because serum creatinine may appear normal even when significant renal impairment exists, it is important to calculate clearance and adjust medication dosages accordingly (Cusak, 2004). The Cockcroft-Gault (1976) formula can be used to estimate creatinine (Cr) clearance:

(Actual body weight[kg ])/ (72 x Serum Cr[mg / dL])

For women, multiply the result by 0.85. Of note, this formula is less accurate in extremely ill patients and those with moderate to severe renal insufficiency.

Pharmacodynamics refers to the end-organ response to a drug. Although not as well understood as pharmacokinetic changes, pharmacodynamic changes can lead to changes in receptor binding, a decrease in receptor number, and altered translation of response to a receptor. One clinical example involves beta-adrenergic blockers and beta-adrenergic agonists. With aging, there is a reduction in beta-adrenergic activity in the cardiovascular and respiratory systems that can result in less responsiveness to beta blockers and beta agonists (Cooney and Pascuzzi, 2009).

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