Drugs In the Aging Body: Just What Goes On When You Swallow that Pill?

The elderly are at greater risk of medication misadventures. The reasons behind this fact are multifactorial, and include many things such as physiologic changes, psychosocial issues, economic issues, religious / family beliefs, access to healthcare, complex pharmacotherapy regimens, and understanding of medication use to name a few. This article explores the differences in drug absorption, distribution, and elimination from the body that occur as we age which may or may not influence medication activity.

Absorption:

The rate of absorption is influenced by the rate the stomach empties into the small intestine.  Stomach emptying is slowed in the geriatric patient. There is little difference in small bowel architecture or transit time. The end result:  There may be decreased onset of action, or decreased time to maximum concentration of the drug in older persons; however, aging does not significantly influence the rate or extent of drug absorption despite many age related differences in GI function.
  • There are always exceptions:
    • decreased calcium absorption due to higher gastric pH
    • analgesic onset may be delayed, but duration will be the same or prolonged.
Distribution:
When looking at distribution, you need to consider what is involved in getting the drug from the gut to the various desired sites in the body.  Changes in geriatrics that can effect distribution are significant.
  • Body composition changes:
    • 15% decrease in total body water
    • 13%-40% increase in body fat
    • Lean muscle mass loss of 0.29-0.12Kg/year
  • Plasma protein concentrations
    • Decreased serum albumin (4.2-20%)
    • Possibly some conformational changes in albumin with age, (which can cause a decrease in drug binding)
The extent of drug distribution into tissues of the body is called the volume of distribution (Vd) in pharmacist lingo.  When medications circulate in the blood and bind to plasma proteins, there could be higher concentrations of free drug (and resultant toxicity) than would be expected in younger persons.   It is important to consider the total albumin load in the geriatric patient when evaluating medications. There are many reasons for altered proteins in the elderly including: underlying illness, decreased calorie intake, decreased protein synthesis by the liver, and altered properties of albumin that can occur in the elderly.  A prime example of this situation occurs with Dilantin, depakote, and salicylate.  It is important to consider the total albumin load on a geriatric patient.
Another plasma protein, AAG has levels that are normal or slightly increased in seniors.  Levels may rise dramatically during illness. Medications which are affected by binding to this plasma protein include: Elavil, Norpace, Tofranil, Lidocaine, Pamelor, Quinidine. To compound matters, most of these drugs are not routinely monitored for serum level…..WATCH for adverse reactions!
When medications are distributed in the total body water (which is decreased in the elderly) there are higher drug concentrations from the same dose which can cause toxicity and or an increase in side effects. Examples of this situation include: alcohol, caffeine, lithium, theophylline, and digoxin. 
Medications that concentrate in body fat have increased storage capacity in older adults and may increase risks of accumulation. Examples include: Valium, Librium.
Metabolism and Elimination:
The declines in the ability to metabolize and eliminate drugs increase with age. There are significant differences between 65 year olds and 85 year olds, the progressive declines continue thru life. The age related declines in renal function are consistently paralleled by reduced drug excretion.
There are several ways to determine renal drug clearance; each has its benefits / drawbacks. In general,  declines follow  the 80/40 rule (average  clearance of an 80 year old is 40ml/min);  the 1% per year decline beginning at age 30 rule (you loose 1% of renal function yearly beginning at age 30), or the 7% per decade rule (average of 7% decline in renal function every 10 years).  There are also calculations that can be used to estimate renal dysfunction and creatine clearance (which is a more specific measure of a person’s ability to eliminate drugs from the body. No matter which estimate is used, there are clinically significant declines noted in all geriatrics.
Similar decreases are seen in liver metabolism of drugs, though the body’s capacity to metabolize medications thru liver enzymes is quite extensive, this can come into play in the frail elderly on multiple medications. Liver size (17%-24%) and blood flow and enzyme activity decrease with age.
Pharmacodynamics:
Pharmcodynamics by definition is the study of how the body reacts to drugs.  Considering the changes discussed above proves inadequate in overall evaluation of medications in the elderly.  There are many physiologic changes that occur with age that also impact medications in the body.  Some medications which have pharmacodynamic  differences in the elderly include:
  • Isoproterenol a single dose needs to increases of 4-6 times normal to increase HR by 25 BPM in an elderly person.
  • Hydralazine usually has a beta blocker ordered with it in younger patients because it causes a compensatory increase in HR & contractility (caused by the vasodilatation)…this is often not needed in the geriatric patient.  Calcium channel blockers may act in a similar fashion
  • Diabetics who become hypoglycemic... The counter regulatory hormones (glucagon, adrenalin, and norepinephrine) which normally trigger tachycardia/palpitations, and tremor are often absent or do not appear until after it is too late in the elderly.
  • Decreased response to atropine, increased response to antipsychotics and tricyclics due to decreased cardio vagal tone
  • Increased sensitivity to diuretics (due to decreased TBW)
  • Increased penetrability of drugs across the blood brain barrier (causing increased CNS side effects of medications that get to the CNS

The take home message regarding medication absorption, distribution, metabolism, elimination, and pharmacodynamics in the elderly?
“In the geriatric patient, assume any new symptom or complaint is the result of drug therapy until you can prove otherwise”

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