See also October 2006 Drug Update “How to Avoid Drug Interactions in the Elderly.”

Drug Metabolism Less Efficient in the Elderly  

"That's one of the reasons that?when dosing medications in older people we tend to start with a really low dose and titrate up slowly to the minimum effective dose." ?Michelle A. Fritsch, PharmD

The aging process affects all 4 mechanisms involved in the processing of drugs—absorption, distribution, metabolism, and elimination. “Oral absorption is affected, because there is typically less gastric acid, the absorptive cells of the stomach tend to be a little less active, and there’s less blood flow to the stomach,” Michelle A. Fritsch, PharmD, Clinical Pharmacy Specialist, Alamance Regional Medical Center, Burlington, NC, tells IMWR.

As for drug distribution, “As we age, we tend to have more body fat and less body muscle and less body water—all of which have really big impacts on what happens to a drug once it’s been consumed,” says Dr Fritsch.

Many drugs are metabolized in the liver. Aging is associated with decreased blood flow to the liver and changes in the makeup of liver enzymes that break down certain kinds of drugs. “One of these enzyme processes actually goes away as we get older,” Dr Fritsch says, “so drugs that are processed by this oxidative metabolism can’t be metabolized, especially in the old-old, people who are around 85 and over.”

Aging takes a heavy toll on the excretion of drugs. “Even if you’re absolutely healthy, your kidney function starts to decline around age 35 or 40 and then continues throughout the rest of your life. By the time you get up into your 80s and 90s, just that natural decline has made a big impact on your renal function.”

Conditions that affect the kidney can further erode function. “If creatinine clearance gets below 60 mL/min, some medications need to be adjusted or not used,” Dr Fritsch advises. “Once it dips below 30 mL/min, you really have to make a lot of dosage adjustments and more carefully choose which drugs to use.”

Pharmacodynamics—the receptor sensitivity in various parts of the body—is, according to Dr Fritsch, “a much more difficult science to measure.” She says that anecdotal evidence suggests that in some individuals, the receptors become less responsive, and more drug may be needed, whereas in other persons the receptors become more responsive, and less drug is needed. “That’s one of the reasons that it can be so unpredictable, and that when dosing medications in older people we tend to start with a really low dose and titrate up slowly to the minimum effective dose. In contrast, with younger people we might be more aggressive and start with a higher dose and then titrate down: in geriatrics, start low, go slow.”