SAN DIEGO—"There is often a wide discrepancy between what we think our patients are taking and what our patients are, in fact, taking," Peter A. Boling, MD, director of the MCV Campus Geriatric Section at Virginia Commonwealth University, Richmond, said at the annual meeting of the American College of Physicians. Studies have shown that almost one third of patients are not taking drugs that are recorded in their chart, and 20% are taking a dose different from what their doctor thought they were taking, Dr Boling stressed.

Medication Reconciliation

Despite the recent focus on medication reconciliation—the process of comparing a patient's medication orders to all the medications the patient has been taking—"We are far from where we need to be in this area," Dr Boling says. "I think it's one of the greatest threats in terms of the safety of the Medicare population."

Peter A. Boling, MD

Among the causes of adverse drug events, some can be more easily corrected by physicians, but others are more dependent on system solutions, says Dr Boling, who is also interim chair of the Division of General Internal Medicine at Virginia Commonwealth University.

"For example, improper drug use or selection is something that we have a lot of say in. One of the things that we don't control so well is multiple providers."

The updated Beers List includes several drugs that are still being frequently prescribed, he says. "I saw a geriatrician give a patient with orthostatic symptoms 100 mg a day of amitriptyline in the last month, so we're still doing some of these things and contributing to the problem," Dr Boling said.

And the patients who are most likely to have adverse drug reactions are older, sicker, and are taking more drugs because of having several comorbidities. And this means they are more likely to have drug interactions.

"The problem we all face is that we don't really know what patient is having which drug–drug interaction," he says. "And adverse drug reactions are often symptomatic, so any new symptom in an older patient should be considered first a drug side effect until proven otherwise."

About 80% of serious adverse events are exaggerations of therapeutic effects (eg, overdiuresis, overanticoagulation, hypoglycemia) rather than side effects. Therefore, you need to "be really careful about that, and don't treat a drug side effect with another drug, unless you absolutely have to have that first drug on board," he says.

There are many reasons for patient noncompliance, but "we have a lot of ability to impact this," Dr Boling says. "We can simplify the regimens, make things convenient—talk to your patients about the need for these drugs. A lot of times patients don't take a drug, because they think it's your agenda, not theirs, so you really need to explain to them why and convince them to take it. Or if you can't convince them, then take it off the list."

Drug Pharmacokinetics

The pharmacokinetics of drugs change a lot with aging. Most biological functions decline in terms of the basic reserves and the abilities of those bodily systems to provide backup support as patients get older. An example is renal plasma flow. "By the time you're 85 or so, it has dropped by more than 50% from baseline," he says.

Although gastrointestinal absorption is usually unaffected, gastric acidity declines in 5% to 10% of patients, which may affect absorption of drugs such as iron. "More important are potential problems created by placing incompatible drugs in the stomach together," Dr Boling adds. "For example, coadministration of multivitamins and levofloxacin [Levaquin] negates absorption of the antibiotic, and coadministration of thyroxin with a number of agents, including calcium, blocks absorption of thyroxin, leading to overprescribing and potential toxicity."

Changes in body compartments with age produce sizable (25%-30%) changes in the proportion of body fat, muscle, and water, he noted. "This alters the distribution of many drugs and can affect clinical practice. In some cases, such as lipophilic benzodiazepines or amiodarone [Pacerone], toxicity is increased as drugs build up in the system, while water-soluble drugs with a decreased volume of distribution like digoxin [Lanoxin] reach toxic levels more quickly at lower doses."

The liver is an essential organ for drug metabolism. There is, on average, about a 40% reduction in hepatic blood flow overall in the older population. But "this is tremendously variable," he stresses.

"So if, for example, you have patients who have severe heart failure that improves with treatment, they're actually going to have a much better hepatic drug clearance, because their portal pressures, their hepatic vein pressures, are going to be less, and the ischemic effects on the hepatic metabolism will be less," he notes. "Conversely, if their heart failure declines, and they go into a decompensated state, they're much more likely to have problems clearing drugs that are oxidized in the liver."

Approximately 60% of all drugs are cleared out of the body through oxidative metabolism in the liver. "Unfortunately, we don't really have a way of measuring your patient's current drug clearance in the liver," Dr Boling says. "What we can do is use the creatinine clearance on lab reports as a guide for drugs that are cleared by the kidney. You should be adjusting any renally cleared drug according to the patient's renal clearance report."

Therapeutic Regimens and Medicare Part D

When putting together a therapeutic regimen, consider the patient's overall prognosis. Dr Boling highlights the following points:

• Base treatment on functional status and prognosis for survival
• Approach a frail 70-year-old person who is debilitated and likely to die within 2 or 3 years from chronic disease(s) differently from an 85-yearold who is functionally intact and likely to live another 8 or 10 years
• If the time it takes to show a difference in meaningful outcomes with a drug in clinical trials exceeds the expected survival, hesitate before adding the drug
• Consider patient preferences; ask what their goals are
• When reviewing and simplifying the medication list, reduce or eliminate drugs with high anticholinergic load
• Make sure you know and record in the chart the name of the person responsible for managing your patient's medications.

He also recommends using ACOVE (Assessing Care of Vulnerable Elders) indicators as a guide:

1. Have a defined, written indication for every drug that you prescribe for the long-term
2. Educate the patient and/or caregiver about any new drug (purpose, dose, timing, common side effects)
3. Maintain a current, reliable medication list
4. Document response to therapy for every new drug within 6 months
5. Conduct a complete drug review at least annually
6. Monitor warfarin therapy carefully with a warfarin flow sheet
7. Monitor diuretic therapy with laboratory testing within 1 week after starting the drug and at least yearly thereafter
8. Do not use chlorpropamide for hyperglycemia
9. Avoid strongly anticholinergic drugs
10. Avoid barbiturates
11. Avoid meperidine (Demerol)
12. Monitor renal function and potassium in patients taking angiotensinconverting enzyme inhibitors.

The arrival of Medicare Part D made the construction of therapeutic regimens even more complicated. However, the legislation has produced some benefits, Dr Boling says. For example, older patients are becoming much more aware of drug costs than was the case before.

Because Part D can be so difficult to navigate, however, Dr Boling stresses that "all physicians should make at least one trip to www.Medicare.gov and run through the process of looking for a Part D plan, so they can see firsthand how complex this program is."

He suggests using an available formulary database, such as ePocrates or Lexi-Comp, to guide your prescribing.

Cost Considerations

Physicians are going to be under increasing pressure in the next 10 to 15 years to limit the cost of healthcare for the elderly and are going to have to learn to be good at "picking out the things that have the most bang for the buck," Dr Boling says.

Consider using generic drugs and selecting lower-cost agents when you can do so without compromising clinical outcomes.

"Also, many high-priced drugs have been heavily marketed based on small, statistically significant differences in clinical trials with very large numbers of subjects," he says. Remember to look at the absolute risk reduction rather than the relative risk reduction and the number needed to treat, which is 1 divided by the absolute risk reduction, he suggests.

ONLINE EXTRA:

Can Polypharmacy Be Avoided?

In general, physicians are essentially committed to polypharmacy in older patients.

"Can we avoid polypharmacy? No, we can't. You just have to be intelligent about how you do your polypharmacy," Dr Boling says. "Do it as least 'toxically' as possible. For many conditions, there's quite good evidence that active treatment does make a difference in a relatively short time frame."

Consider Drug Efficacy

Drug efficacy varies by diagnosis, according to Dr Boling, and this should affect your approach to treatment.

CVD

When it comes to cardiovascular disease (CVD), plenty of good evidence shows that patients' risk for CVD increases by 75% by age 75. And since it is in the older population that you get the biggest "bang for the buck" when treating hypertension, if you have a relatively healthy older patient, treat systolic blood pressure (BP), he says. There is also good evidence that lowering BP is likely to reduce the incidence of stroke within a relatively short time (2-4 years).

Diabetes

The prevalence of diabetes is rising in the older population. The majority of new diagnosis of diabetes in adults occurs in 1 of 2 age-groups: (1) 50 to 65 years or (2) 80 to ≥85 years, Dr Boling says.

"If you have a relatively frail older person in your practice who doesn't have a long time to live, I would argue that, unlike the pay-for-performance guidelines aimed at lowering hemoglobin A1c to 6.5%, you're unlikely to produce a meaningful benefit from these patients unless you've got about 10 to 15 years to work with in terms of their life expectancy," he says.

Osteoporosis/Osteoarthritis

In contrast, osteoporosis therapy does not take a long time to produce a meaningful change, with respect to fracture reduction, which is a very important end point in frail older people, he notes.

Osteoarthritis is a prevalent disease among the elderly and a disease for which we have very poor therapies, Dr Boling says.

"We don't have drug therapy that's meaningful for osteoarthritis, and it is going to have a big impact," he stresses.

In addition, the literature is rife with evidence of renal failure and gastrointestinal bleeding in older patients who take nonsteroidal antiinflammatory drugs to treat the pain associated with osteoarthritis.

Several of Dr Boling's patients have told him that the cyclooxygenase-2 inhibitor that was taken off the market (rofecoxib [Vioxx]) "was actually really good for them," he says. "They had a lot of pain relief from it and, unfortunately, we didn't get to have the conversation as to whether they would accept a 50% increase in CV event risk in exchange for having daily pain relief."

Alzheimer's Disease

By the time a person is 85 years old, the prevalence of Alzheimer's disease (AD) is about 30%, "Meaning that as we go into the baby-boom generation, if we are successful in keeping people alive and unsuccessful in finding a cure for this disease, we're going to have a fairly large number of demented people," Dr Boling says. At this point there are no truly effective therapies for AD, he adds. "What we do have is palliative therapies."

Dr Boling points out that "there's a debate going on in geriatric medicine"—"should we be giving cholinesterase inhibitors to a large number of demented older patients with AD? I'm going to say that in many cases the answer probably is yes, as long as we can afford to do it."

He concludes, "I don't think the palliative pharmacotherapy of this disease is any less beneficial than the palliative pharmacotherapy of all sorts of other diseases that we seem comfortable with providing on a regular basis. There are examples of diseases for which there is evidence of benefit."