Pharmacology is not one-size-fits-all. If you’ve read this article on pediatric pharmacology, then you definitely understand this concept. Now we’re going to look at the other end of the spectrum to discuss how aging affects medication administration in the elderly.
Recall that pharmacokinetics is essentially what the body does TO the drug when it is administered. The four pillars of pharmacokinetics are: absorption, distribution, metabolism and excretion. Today we’ll be talking about the age-related changes that occur in all of these pillars. The short version is that many times drug dosages will need to be lower in the elderly. The name of the game is “start low and go slow.” Complexities of pharmacology in the elderly is also often compounded by the presence of multiple disease conditions leading to polypharmacy. Let’s dive into the details.
Absorption is the process of the drug moving from the site of administration into the bloodstream. Though there are significant changes to gastric emptying time, small-bowel surface area and gastric pH, in most cases the absorption of drugs is not significantly different in the elderly.. In general what it does change is how long it takes for the drugs to have an effect. However, there are always exceptions so here are a few prime examples.
- Decreased gastric emptying leads to altered absorption of some medications such as levodopa and digoxin.
- Decreased active transport leads to a decrease in the transport of vitamins and electrolytes.
- Decreased intestinal surface area leads to a general decrease in drug absorption for some medications (digoxin is another prime example of this).
- Increased gastric pH can affect medications that rely on a specific pH level.
- An example is calcium carbonate, which needs a more acidic environment for optimal absorption. For this reason, elderly adults are typically prescribed calcium citrate which dissolves more easily in higher gastric pH levels.
- Another clinically significant example is enteric-coating which is utilized for the purpose of extended release. The coating is designed to remain intact in the low pH environment of the stomach, and then dissolve in the higher pH of the small intestines.
- In the elderly, where gastric pH is higher, these medications can have an “early release” causing adverse GI effects.
What about the transdermal route?
Transdermally delivered medications are typically considered beneficial for the elderly because of the steady rate of administration and ease of use. Some examples include fentanyl, nitroglycerine, estradiol, rivastigmine and scopolamine. Some of the advantages of transdermal administration are the circumvention of hepatic first-pass metabolism, decreased GI adverse effects, higher likelihood of compliance and more consistent drug concentrations.
Though skin definitely changes with age, studies have shown that these changes in lipid structure and hydration really only affect medications with hydrophilic properties. If dose alterations are needed in the elderly, it’s typically due to age-related cardiovascular, renal, and hepatic changes.
Distribution is the process of transferring a drug from the bloodstream to the tissues where it can exert its effect. As we age, total body water decreases while body fat increases. The distribution of highly lipophilic drugs is therefore increased. Great examples are risperidone, atorvastatin, ciprofloxacin, azithromycin, and propofol. So what does this mean for your patient?
Lipophilic drugs may have an increased half-life when body fat is higher, leading to increased levels and prolonged effects of these types of medications.
Distribution is also affected by the presence or absence of plasma proteins. As we age or are malnourished, serum albumin decreases. This leads to changes in the binding of some medications. So if your elderly patient has malnutrition, for example, this reduction in serum albumin can lead to higher levels of unbound drugs like warfarin and phenytoin. And this, in turn, can lead to serious adverse effects and toxicity.
In general, metabolism is the process that drugs go through that makes them either more active or less active…though generally metabolism makes drugs less active. The process of metabolism converts the compound from its original state (which is active) and converts it into something else (which is less active and then…able to be excreted from the body). A key player in metabolism is the liver. Not only does the liver metabolize many medications, it is also responsible for something called the “first pass effect.”
When you take a medication by mouth, it is absorbed through the intestinal mucosa and then enters hepatic circulation and taken directly to the liver for metabolism…even before it goes to the heart for circulation. In some cases, the first-pass effect can reduce a medication’s efficacy by up to 90% when compared to IV administration. This explains why IV doses are sometimes so much smaller than PO doses (A great example of this is midazolam. A common IV dose for pediatrics is .025 to .05 mg/kg for procedural sedation vs .25 – .5 mg/kg. So if the child weighs 30 kg, the low-end dose would be .75mg IV vs 7.5 mg PO.
In elderly patients, metabolic activity is reduced and so is the first-pass effect. For these reasons, decreased doses are often needed in your elderly patients. Some examples of medications that rely on hepatic metabolism and will require scrutiny are ibuprofen, diltiazem, warfarin and levodopa. Remember, start low and go slow!
Elimination is the final pillar of pharmacokinetics. The key player here is the renal system and aging has a significant impact here. After age 40, creatinine clearance starts to decline along with GFR and tubular function. The result is many drugs have reduced elimination by the kidneys. So, any medication that relies heavily on renal clearance will need to be scrutinized for proper dosing. Some great examples of these drugs are morphine, metformin, gentamicin, gabapentin, digoxin, and diuretics like furosemide and spironolactone. Again, with the elderly we start low and go slow!
Let’s talk pharmacodynamics
In addition to the pharmacokinetics, pharmacodynamics come into play as well. The key takeaway here is that elderly individuals will be more sensitive to the CNS effects of medications, especially if they have underlying cognitive impairment. Take diphenhydramine, for example. Elderly patients are more sensitive to the CNS effects of this medication, which is an anticholinergic. One of the main adverse effects the elderly can have with diphenhydramine is acute confusion that can be quite pronounced. They are also likely to more strongly experience the other adverse effects such as dizziness, urinary retention, tachycardia and blurred vision. Be very wary of giving diphenhydramine to your elderly patient and consider alternatives when they are available.
What is a BEERS drug?
A term you may hear when learning about the elderly and pharmacology is Beers drug or Beers List. And no, it doesn’t mean it comes in an ice cold bottle with a wedge of lime. Beers Drugs are those that are marked as potentially inappropriate for use in older adults. The goal is to increase medication safety with this special population that is prone to polypharmacy. Diphenhydramine (and other anticholinergics) are on this list due to the risk for cognitive decline. Others include ACE inhibitors due to risk for hyperkalemia, warfarin due to the increased risk of bleeding and benzodiazepines for the increased risk of falls. There are quite a few medications on the Beers List, and you can view recent additions and updates here or in the Davis Drug Guide if you happen to have an online account or reference book.
One of the highest pharmacologic risks for the elderly is polypharmacy and heightened risk for adverse interactions and effects. The practice of “deprescribing” involves the practitioner evaluating the patient’s medical condition and current pharmacologic regimen to remove as many medications as possible. The process of removing medications is often not as cut-and-dried as stopping them altogether. The practitioner and patient must work together to taper or withdraw as appropriate with ongoing monitoring conducted as needed.
Studies show that deprescribing leads to:
- Fewer medications overall, which tends to improve adherence.
- Improving or preserving cognitive function
- Reducing fall risk
- Reducing risk for hospitalization and even death
- Adherence can be challenging in the elderly population for a variety of factors A 1998 study showed that adherence to pharmacologic regimens varies based on the drug dosage, the form of the drug, cost, physician-patient communication and insurance coverage.
- Complicated regimens and cognitive decline also play a role.
- Swallowing difficulty. Many elderly patients have difficulty swallowing, so may avoid taking pills in their original form. These patients may need medications crushed and added to food such as applesauce or pudding, which can be quite bitter tasting and decrease medication adherence. Patients may not understand they should not crush enteric coated or extended-release tablets, leading to serious adverse effects and even toxicity.
- Medications that require close monitoring, such as warfarin, may be utilized inappropriately in patients who do not have the resources for regular visits to their physician or lab.
What can the nurse do?
A 2017 systematic review outlined specific nurse-led interventions to improve medication adherence and safety among this patient population. These include:
- Patient education (always!). Make sure you are teaching the appropriate person and utilize “Teach Back.”
- Provide written easy-to-follow instructions and schedules.
- Utilize medication management tools such as electronic pill dispensers or pill organizers that separate medication for each day of the week and even AM/PM.
- Reminders via telephone or electronic devices; there are several apps created specifically for this purpose.
- Assessing all medications with each home visit.
So there you have it! Your basic guide to pharmacology and the elderly patient. Looking for the very basic info?
Here’s your TL;DR:
- Physiologic changes associated with aging lead to alterations in absorption, distribution, metabolism and excretion of medications.
- The name of the game is to “start low and go slow.”
- Beers List flags medications that may be inappropriate for the elderly
- The goal of deprescribing is to enhance medication safety and adherence in the elderly.
- Nurse-driven interventions can improve medication adherence and safety.
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