Healthy, Older and Wise – Just Say No to Drug Combos

Yet, far from being a fountain of youth, prescription drugs – especially in combination – may well be hastening the problems of old age: physical frailty, loss of vital-organ function and even mental decline.

The tendency of doctors to dole out multiple drugs to the elderly is worrying because this population group is getting larger by the day. Today, 13 per cent of the US population is over 65, a figure set to rise dramatically in the coming years. Yet, seniors consume, on average, 30 per cent of all prescription drugs (Health Prom Dis Prev, 1992; 8: 127-41). In the UK, the over-65s account for 18 per cent of the population, but nearly half of all prescription drug use (Pharm J, 1997; 259: 686-8).

And these figures are conservative as drug use among the elderly is believed to be grossly underreported.

Doling out drugs

The problem lies in the way doctors approach healthcare in the elderly, and their sketchy knowledge of which drugs are both effective and appropriate for this age group. A recent large-scale study of more than 765,000 seniors showed that more than one-fifth of their prescriptions were inappropriate for their age group (Arch Intern Med, 2004; 164: 1621-5). Ten years ago, a widely publicised report revealed that nearly a quarter of elderly Americans were being prescribed one or more medications that were countraindicated for this patient population (JAMA, 1994, 272: 292-317).

But the most dangerous practice of all – practised all over the world – is polypharmacy, where several different drugs are prescribed at once without sufficient understanding of how these drugs react in combination.

Most older Americans, for example, take an average of three to five drugs (J Am Geriatr Soc, 2001; 49: 277-83), and that doesn’t include over-the-counter medications or herbals. In Canada, 91 per cent of older patients are taking one or more drugs (prescribed or over the counter) – the average per patient was more than four apiece (Ann Emerg Med, 2001; 38: 666-71). In the UK, at least a third of patients over 75 are taking four or more prescription drugs (BMJ, 2004; 329: 434). An Australian survey of more than 200,000 veterans found that:

• more than half were taking more than five separate drugs
• one-fifth were taking more than 10 drugs
• around one in 14 was taking more than 15 drugs
• one in 30 was taking 20 drugs (Aust NZ J Public Health, 1997; 21: 469-76)

While this kind of reckless prescribing used to be confined to nursing homes, it’s now a risk faced by anyone over the age of 50. Besides ignoring the inherent dangers of interactions between drugs, doctors increasingly prescribe drugs ‘off label’ – that is, for conditions and at dosages different from those approved, a well-known major cause of adverse drug reactions.

As the number of drugs taken increases, the risk of adverse effects increases exponentially. Compared with taking only one drug, the risk of ill effects when taking five increases by a further 4 per cent. But if 16 drugs are taken, the added risk skyrockets to 54 per cent (Clin Geriatr Med, 1990; 6: 293-307).

Polypharmacy: a new illness

So common are drug side-effects that doctors now recognise ‘iatrogenic disease’ – doctor-induced disease – from prescribed drugs as a leading cause of illness and death.

Indeed, the Journal of the American Medical Association, the leading scientific publication for the US medical profession, announced that adverse drug reactions were the leading cause of death in hospitalised patients, after the other big killers: heart disease, cancer, stroke, lung disease and accidents. Also, adverse drug events in older patients led to hospitalisation in 25 per cent of those 80 years and older (JAMA, 1998; 279: 1200-5).

In the US, it’s been estimated that, for every dollar spent on drugs in nursing homes, another is spent treating the iatrogenic illness caused by those medications (Arch Intern Med, 1997; 157: 2089-96).

Worse, doctors may mistake an adverse drug effect for a new illness, and end up piling on even more drugs to an already overcrowded regime – the so-called ‘prescribing cascade’ – which, of course, leads to even more side-effects (BMJ, 1997; 315: 1096-9).

The older body

Most medicines are tested on healthy people in their 30s and 40s because, like children, the elderly are not considered ideal subjects for medical study. This is because an older body reacts differently to medication.

In the elderly body, four aspects make drug use potentially risky:

• absorption
• distribution
• metabolism
• excretion

Contrary to typical belief, absorption is not generally affected by age. Older people absorb medications fully, though perhaps more slowly. But once in the system, drugs may behave differently from how they would in a younger body.

In older people who are overweight, fat-soluble drugs can accumulate in fatty tissue and reach toxic proportions. Similarly, the uptake of water-soluble drugs may be slowed by increased fatty tissue, but their effects are greater and longer-lasting. In the elderly, the metabolism of drugs in the liver and excretion through the kidneys may also be slower or less complete, again with more risk of toxicity and damage to those organs.

Breaking the habit

Doctors and elderly patients – and the patients’ families – need to work together to break the habit of polypharmacy. Sadly, many physicians are loath to change their ways. A study from Australia showed that, even when general practitioners were presented with evidence of their own inappropriate prescribing habits over a two-year period, they still did not change their ways (BMJ, 1999; 318: 507-11).

This entrenched attitude makes it more incumbent upon the older patient himself to be a strong medical consumer and do his own homework about each drug being taken (see box), and to insist that your doctor cut out any drugs you don’t need.

Around half of the most popular prescription drugs (such as sedatives and mood enhancers) interact with alcohol (Generations, 1988; 12: 9-13). The older patient needs to be especially vigilant about this interaction, even with over-the-counter remedies, as many of these themselves contain alcohol.

Not prescribing drugs for self-limiting or lifestyle health problems is also important. Many of the ailments affecting seniors are linked to behavioural or lifestyle factors such as smoking or alcohol consumption. Likewise, many of the degenerative diseases that plague older adults can be traced back to six factors of unhealthy ageing:

Altered mitochondrial function due to oxidative stress. Mitochondria are the energy powerhouses of the cell, where nutrients are broken down to release energy for cell repair, defence mechanisms, neuromuscular function, and other processes that maintain the body and help resist ageing. Mitochondrial disorders such as fibromyalgia, heart problems, immune deficiencies, and central and peripheral nervous system problems such as Alzheimer’s and dementia are associated with accelerated ageing (N Engl J Med, 1995; 333: 638-44).

Increased protein glycation. In this process, blood sugar (glucose) is turned into glycated proteins, including glycohaemoglobin, which is involved in the control of blood sugar in diabetics – but too many of these proteins can lead to poor glucose control. Other proteins in the body become glycated when there is poor control of insulin and glucose metabolism. This can lead to periodontal disease and tooth loss (J Periodontal Res, 1996; 31: 508-15), skin ageing and wrinkling (J Clin Invest, 1993; 91: 2463-9), and an increased risk of heart disease (J Clin Invest, 1995; 96: 1395-402).

Chronic inflammation. This begins in the gut, triggered by allergens or parasites, and can give rise to local and systemic immune reactions with gut-associated lymphoid tissue (GALT). Among genetically susceptible individuals, chronic inflammation is associated not only with gastrointestinal and liver-related disorders, but with the risk of Alzheimer’s and heart diseases as well (Neurology, 1997; 48: 626-32; N Engl J Med, 1997; 336: 973-9).

Poor metabolism of homocysteine (an amino acid) increases the risk of heart disease (JAMA, 1997; 277: 1775-81), stroke and dementia among certain individuals.

Compromised detoxification means that toxins accumulate in the body, including drugs as well as environmental pollutants that may be toxic in themselves, and also contribute to free-radical production.

Altered immunity may result from all of the above. As immunity declines, susceptibility increases to infectious agents as well as to allergens.

These problems can all be modified through diet and exercise (see boxes on page 2 and above).

If your doctor doesn’t tell you – or, more likely, doesn’t know – you also need to find out which drugs are not appropriate for seniors (see box, page 3). It’s now known that one in four and one in seven older patients are receiving at least one inappropriate medication (Ann Pharmacother, 2000; 34: 338-46). The most often prescribed risky drugs are long-acting benzodiazepines (tranquillisers and sleeping pills), the antiplatelet drug dipyridamole (Persantine), the pain reliever propoxyphene (Darvon) and the tricyclic antidepressant amitriptyline (Elavil).

Staying alert for gradual changes that may signal a harmful side-effect is essential. Important ‘red-flag’ symptoms include changes in mood, energy, attitude or memory. Too often, these alterations are overlooked, ignored or just chalked off to ‘old age’ or senility. But virtually every heart drug, blood pressure drug, sleeping pill and tranquilliser can trigger these symptoms. So, when a psychological symptom appears – in yourself, a senior patient or a loved one – look to the medications first.

Cutting down on drug use

By asking a few simple questions, you can avoid the prescribing cascade. If you don’t feel confident enough to challenge your physician, take a supportive family member with you.

• Is this illness minor or self-limiting? If so, it may be best to go without drugs.
• Can I get better with lifestyle changes? Losing weight, stopping smoking, curtailing alcohol use and more frequent exercise can all provide substantial benefits, often working as well as – or even better than – prescribed drugs.
• How long has it been since the doctor has reviewed the drugs I am taking? Researchers suggest regularly bagging up all the medicines you’re using (including over-the-counter ones) and taking them to your doctor for a review. Check whether any of the drugs you’re taking can be discontinued.
• Do I need all these drugs? Chances are, the answer is no. Simplifying your drug regimen to include only those that are proven and essential will reduce the risk of drug-induced illness.
• Can the dose be reduced? Challenging your doctor on the dosage and frequency of the prescribed drugs can often result in a reduction, without any loss of benefit.
• What are the adverse effects of this/these drugs? Make sure that your physician has given you a comprehensive list of the potential adverse effects of your medications. Read all the information that comes with a drug so that side-effects are not ignored or wrongly put down to old age.
• Is there a less toxic drug that can do the same thing? There is almost always an alternative medication. Insist on the safest drug possible.
• Should I report this adverse effect? The answer is always yes. Underreporting of adverse drug reactions, or wrongly attributing such symptoms to old age, means that the extent of the problem of polypharmacy will remain largely hidden.

Healthcare in the over-65s rests on the false assumptions that to be old is to be sick and that medicine will cure these problems. To reach your three score and 10, you have a better prospect by looking to your diet and exercise, and saying no to drugs – especially a handful of them.

When prescribing for the elderly, ‘start low and go slow’ is the golden rule. Starting with a third to half the recommended dosage may help eliminate potential ill effects (Geriatrics, 1996; 51: 26-30, 35). In addition, there’s a whole range of medications considered inappropriate for the elderly.

Many produce ‘anticholinergic effects’: they disrupt parasympathetic nervous system function, resulting in confusion, blurred vision, constipation, dry mouth, lightheadedness, voiding difficulties and loss of bladder control. The list below was culled from the Beers list of inappropriate drugs for older patients (Arch Intern Med, 1991; 151: 1825-32) and other data (Can Med Assoc J, 1997; 156: 385-91).

• Antiarrhythmics (e.g. disopyramide): may induce heart failure, strongly anticholinergic
• Antidepressants/antipsychotics (e.g. amitriptyline, doxepin, imipramine): highly anticholinergic and sedating
• Antidiarrhoeals (e.g. diphenoxylate): drowsiness, cognitive impairment and dependence
• Antiemetics (e.g. trimethobenzamide): tremors, restlessness, changes in breathing and heart rate
• Antihistamines (often, over-the-counter drugs used to treat the common cold): strongly anticholinergic, wrongly used to induce sleep; if taken for seasonal allergies, go for the lowest effective dose
• Antihypertensives (e.g. methyldopa, reserpine): methyldopa can slow heart rate and cause depression; reserpine causes depression, erectile dysfunction, sedation and lightheadedness
• Barbiturates (all except phenobarbital): highly addictive, more side-effects than other sedative hypnotics; should not be started as a new therapy except for seizures
• Benzodiazepines (e.g. chlordiazepoxide, diazepam, flurazepam, triazolam): prolonged sedation, increased risk of falls and fractures; triazolam may cause mental and behavioural abnormalities
• Gastrointestinal antispasmodics (e.g. belladonna-containing Donnatal, clidinium, hyoscyamine, propantheline): highly anticholinergic, substantially toxic in general
• Genitourinary antispasmodics (e.g. oxybutynin): anticholinergic effects; use the lowest effective dose
• Hypoglycaemic agents (e.g. chlorpropamide): slow to clear from the body; prolonged and serious hypoglycaemia, serious oedema
• Meprobamate (e.g. Miltown, Equanil): for anxiety, highly addictive and sedating, may contribute to falls and fractures
• Methylphenidate (Ritalin): agitation, stimulation of the central nervous system, seizures
• Narcotics (e.g. meperidine, pentazocine, propoxyphene): addictive; hallucinations and confusion; ineffective for pain relief
• NSAIDs (e.g. indomethacin, phenylbutazone, ketorolac, mefenamic acid, piroxicam): indomethacin causes serious central nervous system effects; phenylbutazone suppresses bone marrow; ketorolac, mefenamic acid and piroxicam increase the risk of upper gastrointestinal bleeding
• Peripheral vasodilators (e.g. cyclandelate, ergot mesyloids): for dementia and migraine; rarely effective
• Platelet-aggregation inhibitors (e.g. dipyridamole, ticlopidine): prevent blood from clotting in stroke or heart attack victims; ticlopidine is no better than aspirin, but is more toxic
• Skeletal muscle relaxants: of questionable effectiveness; anticholinergic effects, sedation and weakness.

A sedentary lifestyle, smoking and hypertension all raise the risk of heart failure to roughly the same degree. But, although less than 10 per cent of women over 75 smoke, more than 70 per cent are too inactive (Arch Fam Med, 1998; 7: 285-9) – in itself a major cause of illness.

Almost all older individuals can benefit from additional physical activity that includes a mix of aerobic exercise (such as walking), strength training (using weights), and balance and flexibility (yoga or tai chi). Older adults who remain active reap many rewards (Am Fam Physician, 2002; 65: 419-26, 427-8), including:

• better heart function
• better circulation
• improved glycaemic control
• stronger bones
• better balance
• less pain
• healthier joints
• better sleep quality
• less fatigue
• sharper minds
• lower risk of colon, breast, prostate and rectal cancer.

Vitamin C, another protective antioxidant, helps prevent cancer and heart disease (Clin Invest, 1993; 71: 3-6) as well as enhances wound-healing, collagen production and immune function (Altern Med Rev, 1998; 3: 174-86). Best taken with cofactors such as bioflavonoids and rutin, or other antioxidants. Daily dosage: at least 1 g

B vitamins in the form of 400 mcg/day of folic acid can lower homocysteine levels, thus preventing atherosclerosis (hardening of the arteries), heart attack, stroke and possibly Alzheimer’s (Can J Cardiol, 1999; 15 [Suppl B]: 35B-8B), and adding vitamin B12 (500 mcg/day) may boost the effect. Together, they can reduce homocysteine by 25-33 per cent (BMJ, 1998; 316: 894-8). Take as part of a B-complex formula. Daily dosage: 400 mcg (folic acid), 50-100 mcg (B12), 500 mg (B5), 50 mg (other B vitamins)

Carotenoids are antioxidants that can slow the ageing process and treat age-related diseases; some 21 kinds have been identified in human blood. Beta-carotene enhances immune function and lowers the risk of cancer and heart disease when 25,000-50,000 mg/day is taken (FASEB J, 1995; 9: A436). Lycopene, abundant in processed tomato products, but also available as a supplement, is the most prevalent blood carotenoid. It can lower the risk of age-related macular degeneration (Arch Ophthalmol, 1995; 113: 1518-23) – as can lutein and zeaxanthin (Am J Clin Nutr, 1995; 62 [6 Suppl]: 1448S-61S) – and help prevent or slow the progression of prostate cancer (J Natl Cancer Inst, 1995; 87: 1767-76). Daily dosage: 15 mg

Vitamin D is an important nutrient for the prevention of many diseases of old age, including brittle bones (N Engl J Med, 1992; 327: 1637-42) and some cancers. Those who spend a lot of time indoors may be deficient. Supplement with vitamin D3, the natural form of this vitamin. Daily dosage: the daily reference intake (DRI) for older people is 600 IU, but have your levels assessed first as too much can be just as damaging as too little

Minerals such as manganese, zinc, selenium and copper assist antioxidant enzymes in the body. Zinc is especially important as levels decline with age, often due to a reduced efficiency of the thymus gland. This can lead to immune deficiency, impaired wound-healing and a lowered resistance to infection. Daily dosage: 30 mg of zinc with 2-3 mg of copper

Coenzyme Q10 can also help protect against oxidation and age-related diseases. This antioxidant is essential for energy production in the mitochondria, especially in the heart. Daily dosage: typically 50-100 mg; for those with cancer, heart disease or immune disorders: 100-400 mg.