Acute Postoperative Pain Management in the Older Patient

Thor Hallingbye; Jacob Martin; Christopher Viscomi


Aging Health. 2011;7(6):813-828. 

In This Article

Pharmacokinetics & Pharmacodynamics: Application to Drug Dosing in the Older Adult

With age, the pharmacokinetics and pharmacodynamics of drugs change. Pharmacokinetics, in simplistic terms, is what the body does to a drug. Absorption, distribution, metabolism and elimination fall into the realm of pharmacokinetics. Hepatic metabolism of drugs relies on two important steps, Phase I and Phase II metabolism. The oxidation, reduction and hydrolysis reactions of Phase I metabolic capability probably decrease with age, but this may or may not be clinically significant.[41] The Phase II reactions of conjugation through methylation, sulfation, acetylation or glucuronidation are likely unaltered as we age.[41] Pharmacodynamics is defined as the effect of a drug on a person. Pharmacodynamics is usually related to specific drug receptors, which can change in function and density with age.[7]

Older adults have a wide range of renal and hepatic function. Decreased hepatic blood flow and mass can lead to reduced metabolism and prolonged elimination especially for drugs with blood flow-limited metabolism, such as morphine. Although the liver experiences a progressive decline in mass, to a large extent it maintains its metabolic capability through its CYP450 system. The consequence of renal impairment on the pharmacokinetics of analgesic drugs typically outweighs the potential impact of reduced hepatic function.[42] For example, renal insufficiency can play a significant role in the reduced clearance and accumulation of both drugs and drug metabolites. Morphine and its metabolites (morphine-6-glucuronide and morphine-3-glucuronide) and meperidine and its metabolite (normeperidine) are probably the most clinically relevant.[43]

Older persons have a highly variable number of comorbidities, and therefore, a potentially higher number of medication interactions to consider. The volume of distribution, defined as the theoretical volume into which a drug distributes to produce a certain plasma concentration, may change depending on various factors, such as renal and hepatic function as well as total body water and fat content. These factors make it difficult to generalize the effect a drug will have on an older individual. Table 3 summarizes pharmacokinetic differences between older and younger persons.[7]

Older adults display pharmacodynamic changes, particularly in the central nervous and cardiac systems. The sedating effects of benzodiazepines can be increased by up to 50% despite the pharmacokinetics being similar between the young and old.[44] Balance disturbances are quite common after benzodiazepine administration and may be related to an exaggeration of baseline differences between young and older persons. Increased sensitivity to opioids appears to be the result of both pharmacokinetic and pharmacodynamic changes.[45] Older persons likely express a lower density of µ-opioid receptors making them more vulnerable to the effects of opioids.[38,43,44] Older patients appear to be more sensitive to the anticholinergic side effects of tricyclic antidepressants and display greater potential for increases in electrocardiogram QT-interval prolongation.[41]

Because of the wide variation of physiological parameters present between older individuals, the adage 'start low and go slow' should be remembered when initiating drug therapy in the older patient.[42]


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.