Polypharmacy, part 2. Risk of drug effects with multiple medications in the elderly: aging changes.

The Bottom Line

  • As people age, changes occur in the way their bodies process medications, and the benefit/risk profile of a medication may change.
  • Polypharmacy can be a potential problem if the medications (and vitamins, herbs and other food supplements) interact to increase, decrease or cancel the effects of different drugs.

In Part 1 of this blog we presented evidence showing how many older adults are likely to be taking multiple medications (polypharmacy). When we combine different medications, there can sometimes be a risk that they can affect each other in unexpected ways. That is, one medication may influence another medication to potentially give you unwanted effects; this is called an interaction. Sometimes these interactions can be negative and we call these adverse events or “side effects”.

In Part 2 of this blog we discuss how polypharmacy affects us as we age. 

Is polypharmacy always cause for concern?

Polypharmacy is not necessarily a bad thing. It is appropriate to take several medications if each one is meeting a specific health need (such as, arthritis, or blood pressure problems). In this case, the benefits outweigh the harms of taking several medications.  However, benefits or harms from a medication may change over time (in the section below, we describe how this happens). 

So how do we know when polypharmacy does not help? Taking multiple medications can be a problem when: 

  • a medication does not provide  a substantial benefit according to your personal goals and needs, 
  • when the medications  increase the risk of bothersome or serious side  effects,
  • the risk of a medication outweighs the benefits.

What does the research show us about polypharmacy and interactions?

On the one hand, there is good news, as taking multiple medications means that effective treatments exist for many of the health problems that seniors have. However, the risk for side effects increases with a greater number of medications, as well as with increasing age. A recent well conducted systematic review showed that adverse effects from medications occur in 58% of people using five medications (1). Older adults are especially susceptible to adverse effects from medications. For example, some medications can cause problems with your memory and other brain functions (called cognitive impairment), urinary incontinence, or impaired balance. This research shows that any of these consequences can increase the risk for falls in an older adult (1). Polypharmacy is also associated with difficulty remembering to take medications on a regular basis (1). 

How do medications interact when treating multiple conditions? 

There are two important things we need to understand about our bodies when we are taking any type of medication. The first thing is how our bodies affect the medications– we call this pharmacokinetics. The second thing is how medications affect our bodies – this is called pharmacodynamics. Both of these processes are keys to understanding the benefits and harms of polypharmacy. We consider these two basic processes as we age.

Pharmacokinetics - how do multiple medications generally affect our bodies? 

One of the most important concerns when taking multiple medications is the risk of interactions. Medications may cause interactions with each other in many ways.  When combined, some medications increase the overall effect on your body. For example, both aspirin and warfarin (a medicine to prevent blood clots) can increase the risk of bleeding. When they are used together, the combined effects of aspirin and warfarin increase the risk of bleeding.  In contrast, certain medications, when combined, decrease the overall effect of each medication. For example, taking an antacid at the same time as an antibiotic, reduces the body's ability to absorb the antibiotic; this interaction reduces the effects of the antibiotic.  So, we can see that when some medications are combined, they may produce a “new effect” or interaction that can be helpful or harmful. 

Every time we take a medication, our bodies go through a series of steps to process the drug, rather like the way we digest food. This process is known as pharmacokinetic. There are several different types of pharmacokinetic processes and these are described below:

  1. Absorption-Tablets and syrups are absorbed through the intestines, creams and lotions through the skin, inhaled medications like "puffers" through the lungs, injections usually through muscle.
  2. Distribution-medications are spread to different parts of the body, depending upon their properties.
  3. Metabolism-The medication is changed or "digested" to make it easier for the body to dispose of it. This usually occurs in the liver but may involve other organs. Sometimes this step is necessary to enable the medication to be effective.
  4. Elimination-This step involves the body disposing of the medication, usually in urine or feces.  

These pharmacokinetic processes serve to raise or lower the amounts of drug available to exert its effect on the body. Interactions may occur when one drug affects one or more of the above processes, and changes the available amount of another drug.

How does aging affect the ability of the medications to affect our bodies (pharmacokinetics)?

As we age, changes which normally occur in these pharmacokinetic processes may affect the risk/benefit profile of medications. This causes older adults to be more vulnerable to medication-related problems. For example, our kidneys work less well as we age; this reduces the ability of the body to eliminate certain medications from our systems (1;2). A medication which is prescribed to a young person may have a different effect as the person ages. This makes it necessary to review the need for, and dose of, that same medication at regular intervals. 

Pharmacodynamics - how do our aging bodies respond to multiple medications? 

Our bodies can also affect a medication such that any benefits or harms are changed.  What a drug does to our bodies is called "pharmacodynamics". Most importantly, how medications affect the condition for which they are prescribed (e.g. lowering blood pressure or blood sugar) is key.  Pharmacodynamic effects can also cause medication interactions. When two or more drugs are combined they may cancel each other out, which may cause one or all of the drugs to have no benefit. On the other hand, when two or more drugs are combined they can increase the effect of one or both, which may result in a greater effect or more side effects (2;3). Drugs can also interact with food, vitamins and herbal products. For example, grapefruit juice affects the enzymes which break down some cholesterol lowering drugs (e.g. atorvastatin). Grapefruit juice acts to  reduce the metabolism of the drug and increases the effect on your body, similar to taking a higher dose. The opposite effect can also occur, whereby some herbal products (like St John’s Wort used to treat mild depression), increases the breakdown of other drugs (e.g. blood thinning medications like warfarin). In this example, the warfarin is less available to the body, and has less effect. Another pharmacodynamic problem is that some drugs can aggravate specific diseases. For example, over the counter decongestants that may be taken during flu and cold season can cause blood pressure to rise. If a person has high blood pressure, it may be unsafe to take decongestants. Check with your health care professional first!  

What is the bottom line about polypharmacy?

Medications can be very helpful but they can also be harmful. Medications may interact with one another and cause increased or decreased effects. How our bodies affect the medications (pharmacokinetics) is one reason we may get interactions or side effects.  Interactions or side effects can also occur because of the effects of the medications on our bodies (pharmacodynamics).  As one ages the benefit and risk profile of a medication may change.  

In Part 3, we will discuss what we can do to assess and prevent problems associated with polypharmacy as we age.

This four-part series of blog posts explores various aspects of polypharmacy. Part 1 defined the issue. In Part 2, we discuss how aging changes the way our body responds to medications, including when taking multiple medications. Part 3 looks at online drug interaction checkers. Part 4 examines medication reviews.

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  1. Patterson SM, Hughes C, Kerse N, Cardwell CR, Bradley MC. Interventions to improve the appropriate use of polypharmacy for older people. Cochrane Database Syst Rev 2012;5:CD008165.
  2. Ramage-Morin PL. Medication use among senior Canadians. Health Rep 2009 Mar;20(1):37-44.
  3. Aronson JK. Classifying drug interactions. Br J Clin Pharmacol 2004 Oct;58(4):343-4.

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