Drug Interactions in the Elderly

Summarized by Robert W. Griffith, MD
September 28, 2007

Summary

The need to identify, manage, and prevent drug interactions is particularly important for older patients. They may be taking a number of medications, and often have several chronic disorders. A holistic, multiprofessional, team-based approach is recommended, assisted by computerized prescribing software with appropriate alerts.

Introduction

Elderly patients are more likely to experience drug interactions than younger people. They take more medications, they have more co-existing diseases, and they may not have an adequate nutritional status. Moreover, there are more of them who have survived severe health challenges - e.g. organ transplants or HIV infections - than younger folk. Fortunately, health professionals' knowledge of the risks of interactions in the elderly has improved, which mitigates the problem somewhat. However, there is room for improvement, as shown in a recent article in the Lancet. Here are some points taken from this article.

The types of drug interactions

It's not enough to examine the effect of one drug on another - a so-called drug-drug interaction. There are drug-disease, drug-food, drug-alcohol, drug-herb, and drug-nutrition interactions. One can also include drug-patient interactions, where the specific genetic make-up in the patient affects their individual response to a drug.

Drug-drug interactions can be pharmacokinetic or pharmacodynamic. In a pharmacokinetic interaction, one drug can influence the other's absorption into the body or the rate of its breakdown, changing the amount of the dose of the second drug that's available to do its work (or produce an overdose or toxic effect). A pharmacodynamic interaction occurs when one drug affects the way another drug produces its effect on the target tissue in the body, either inhibiting or enhancing the effect.

An example of a pharmacokinetic interaction is when ciprofloxacin (an antibiotic) is given with olanzapine (used for mental disorders); the antibiotic blocks the liver enzyme that breaks down olanzapine, producing blood levels that cause muscle spasms and falls. A pharmacodynamic drug interaction is exemplified when ciprofloxacin is given together with glibenclamide (an antidiabetic); ciprofloxacin reinforces gibenclamide's effect on the blood sugar, producing profound hypoglycemia.

Drug-disease interactions are likely with chronic disorders of the liver (responsible for breaking down drugs) or the kidneys (responsible for excreting drugs and their breakdown products). Patients with such conditions may require lower-than-usual doses of many drugs. More rarely, a disease can affect the tissues where a drug has an effect; an example of this is the administration of metaclopramide (used to treat an inactive stomach) in Parkinson's disease patients, which can worsen the Parkinsonian symptoms. Australian researchers have reported that actual drug-disease interactions are two to three times more frequent than actual drug-drug interactions.

Drug-nutrition interactions can occur when inadequacies in the diet can allow deficiencies to develop. For instance, too little protein can result in a low serum albumin level; drugs that are large carried bound closely to protein would then be present in greater amounts of their 'free' or immediately active form, producing overdose effects. An example is when the anti-epileptic phenytoin is given to a patient with a low albumin level, causing confusion, insomnia, and staggering.

Overweight and obesity, perhaps related to nutrition, can also affect the dose of drug required for a desired effect. A small thin elderly person often requires a lower dose than a large, overweight patient; ignoring this may result in side effects in the small subject, or a lack of effect in the overweight patient.

Drug-herb interactions are increasingly common, because patients have turned to alternative medicines more often in recent years, and they don't inform their doctors of the herbs and supplements that they are taking. This is particularly the case with older patients. For example, taking gingko along with aspirin causes a decrease in the function of the blood platelets, so that there's an increased risk of bleeding. People often believe that alternate medications are, by nature, harmless and unable to produce or precipitate side effects.

Drug-alcohol interactions are usually an example of drug synergy; the soporific effects of alcohol potentiate the sedative action of bromazepam and other minor tranquilizers (see link below).

Inadvertent Drug-Drug Interactions

The risk of drug interactions increases with the number of drugs taken. Physicians are often unaware of all the drugs their patients are taking; sometimes a patient will visit two doctors, each of who prescribe medications. Patients may visit different pharmacies, rendering the pharmacy software-generated warnings virtually useless. And older people are notorious hoarders - they may keep unused medications for years, and turn to them when they feel symptoms warrant their use.

An Approach to the Problem

The authors of the article suggest that physicians should consider the following:

1. Concentrate on potential drug-drug interactions that are common, which involve drugs with a narrow dose range - e.g. digoxin, phenytoin, or warfarin (a blood thinner) - and where lab monitoring tests are usually available. Such interactions are detected by computer software systems.

2. Think carefully before prescribing a drug to someone who is already taking nine or more drugs, or has 5 or more comorbidities (co-existing medical conditions) - these are 'exposure' levels at which a new drug-drug or drug-disease interaction is highly likely.

3. Avoid, if possible cascade interactions. This is when an adverse drug reaction is interpreted as a new medical disorder, and a new drug is prescribed to treat the symptoms. A study has provided a good example. Patients with Alzheimer's disease who are prescribed a cholinesterase inhibitor, such as Donepezil (Aricept®) or Rivastigmine (Exelon®), may develop urinary incontinence; this may lead to a prescription for an anti-cholinergic drug, which would not have been necessary if the first drug had been correctly selected or dosed.

If an interaction is diagnosed

This is what the doctor may do in such circumstances:

1. If possible, discontinue one or other of the drugs at fault. Otherwise, try changing the dose or the time of administration.

2. Review all the drugs the patient is taking for their appropriateness, and to ensure the lowest effective dose is being used.

3. Consider substituting the suspect drug with another of similar efficacy but a lower chance of interaction.

4. Order monitoring of drug serum levels, if such tests are available.

5. Be ready to discontinue drugs if a cascade interaction is suspected.

Prevention is better than cure

One of the best preventive steps is achieved by computer systems that screen for interactions at the time of electronic prescribing, and show alerts before the prescription is filled. This should be done consistently and continuously, and linked to a source for intelligent recommendations about alternative therapies. There is a risk that health professionals may ignore or over-ride such alerts, but, with better education, such instances will become fewer.

The optimum health management team for geriatric patients should consist of a physician (preferably a geriatrician), nurse, and pharmacist. Working together they should be able to avoid most drug interactions.

Source

• The challenge of managing drug interactions in elderly people. L. Mallet , A. Spinewine , A. Huang, Lancet, 2007, vol. 370, pp. 185--191

Related Links
Drug Interaction Checker Tool
Top Ten Drug Interactions in Seniors
Drug-Alcohol Interaction Risk for Seniors

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