Positive Options for Living with Lupus (10 page)

The Problem of Polypharmacy (Taking a Lot

of Drugs at Once)

Before looking at the drugs used to treat the various symptoms associated with lupus, here’s a word about taking drugs in general.

“Polypharmacy” means “many drugs,” and it refers to problems aris-ing from the unwanted duplication of medications or from adverse interactions between drugs. Most of us get used to taking aceta-minophen for a headache, a course of antibiotics for a bladder infection, or an antihistamine for hay fever, but these common medications are all taken in response to recognized symptoms, taken alone, and stopped once the symptoms subside (or once the course is complete, in the case of antibiotics). The drugs prescribed for lupus are less symptom-specific. In addition, lupus patients have the same common ailments requiring medication as the rest of the population, so at times they may find themselves with a veritable pharmacy laid out on the dressing table. What’s more, the fatigue and emotional ups and downs that often accompany lupus can play havoc with memory and attention, potentially causing problems with a patient’s drug regimen.

The advice of the experts is as follows: Write your medication schedule down—which pill, how many, at what time of day, and whether it is to be taken before or after food. Ideally, check each one off the written list as you take it. You should probably also make a note of any drug that doesn’t agree with you. Some drugs can POL text Q6 good.qxp 8/12/2006 7:39 PM Page 58

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increase photosensitivity, for example, already a problem for many with lupus; others produce side effects such as an upset stomach or rashes in some people. If you experience side effects from any drug, make sure to record which one and exactly how it affects you, and make sure it is listed as problematic on your medical and dental records.

The problem of polypharmacy is not unique to people with lupus. The preventive regimens designed to protect against heart disease and other conditions of old age—for example, menopausal symptoms, high blood pressure, raised cholesterol, and diabetes—

Randomized Clinical Trials (RCT): The Therapeutic Gold Standard The idea of using the scientific method to test the effectiveness of drugs or other medical procedures is a relatively modern concept.

Curing people has historically been as much about faith and luck as it has about medical understanding or effective treatment. But as the causes and mechanisms of disease emerged from mystery and super-stition, so the physician’s ability predictably to alter the course of disease—to intervene—increased.

The first example of what is now regarded as the gold standard for clinical trials—the randomized, controlled trial, or to give it its high-carat denomination, the randomized, placebo-controlled, double-blind trial—took place just after the Second World War in 1948 when Austin Bradford Hill set up a trial of streptomycin, an antibiotic derived from soil fungi discovered a few years previously, to measure its effectiveness in tuberculosis. Patients with advanced pulmonary (lung) tuberculosis (TB) were randomly assigned to one of two treatment groups. If doctors are allowed to choose which patients receive a new active drug and which are allocated to the control group, there is always the risk that they will put the patients with the best prognosis into the active group, thus skewing the outcome. When, in addition to patients being randomly assigned to either the treated or control group, patients don’t know whether they are on the active drug or not, the trial is known as “blind.” If, in addition, the medical team looking after the patient and running the study is not told which patient is in which group, the study is “double-blind”; neither the patient nor the medical staff know who is in which group. This prevents any hidden psychological bias for or against the new treatment. Clinical studies usually POL text Q6 good.qxp 8/12/2006 7:39 PM Page 59

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mean that many of us take a lot of pills starting in middle age. Lupus patients are old hands at it long before that.

Charlotte’s Story

Early in the summer of 1976, Charlotte, a senior in high school, was outdoors studying for final exams. She developed a f iery rash and felt generally unwell, but somehow she managed t o keep going and waited to visit the doctor until summer vacation started. At once he r ecognized the classic butter fly rash, organized a battery of tests, and told Charlotte she had lupus. The symptoms subsided over the summer with little medication.

measure the effect of a new treatment against a comparator: either the standard treatment of the day—it would be unethical to withhold all treatment from a sick person for research purposes—or, in nonfa-tal conditions, unlike TB, against a nonactive dummy pill (a placebo) to conceal from them whether they are taking the active treatments or not. Patients with some illnesses—depression, for example—may show marked improvement when receiving a placebo. This response to treatment, albeit with a nonactive compound, is called the placebo effect.

In the Hill study of streptomycin, 107 patients were enrolled. When the results were unblinded it was discovered that 14 of the 52 patients on standard treatment had died (remember that these were very ill people), but that only 4 of the 55 patients who had been given the active drug had died. Streptomycin really worked.

The supremacy of the RCT was reinforced in the early 1950s by trials of the Salk polio vaccine. It was tested using an elaborate double-blind trial on nearly two million children in the U.S. These early successes, together with early failures of clinical testing procedures—

for example, thalidomide, an effective drug for morning sickness in early pregnancy, was found to have damaged the fetus developing in the womb—led to the establishment of laws in Europe and the United States governing the testing of experimental drugs. These days, before a drug is approved for general use it must be tested against these standards. As David Healy says in his book The Antidepressant Era (Harvard University Press, 1997), “Randomized, placebo-controlled, double-blind trials are the appropriate means, indeed almost the only scientific means, to establish the efficacy of a treatment.”

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Charlotte took a year off and went backpacking across Europe.

Somewhere in what was then Yugoslavia she developed cystitis (bladder infection) and found herself trying to communicate with a local doct or in the rudiment ary German the y bo th spoke. “Keine penicillin” (no penicillin) insisted Charlotte, who knew she was allergic t o the drug. U nfortunately she couldn’t remember the name of the antibiotic that her family doctor did prescribe for her. She certainly didn’t know the German word for lupus. The local doctor prescribed a sulfa drug, and within two days Charlotte broke out in a rash—not just on her face, but on her hands, lower arms, and ankles. Even though it was No-vember, the drug had potentiated Charlotte’s photosensitivity.

Nonsteroidal Anti-Inflammatory Drugs

(NSAIDs)

The acronym NSAIDs—pronounced “en-sayeds”—is used freely in talking about dear old aspirin and its younger siblings. They are used to treat such a wide range of conditions that two important things about them are easily overlooked: They kill pain, and they reduce inflammation without belonging to the
corticosteroid
family of drugs
.
Corticosteroids are also powerfully anti-inflammatory and very effective in the treatment of lupus (see Chapter 7). However, they pack a payload of side effects, and they also have some rather disreputable relations: the anabolic steroids used by some athletes to enhance performance.

In the first half of the twentieth century, high doses of aspirin—

the oldest member of the NSAID family—were the standard treatment for rheumatoid arthritis, juvenile arthritis, and lupus patients with arthritic symptoms. However, once the dosage and side effects of these drugs were studied in properly controlled trials it emerged that good old aspirin had quite a few serious side effects. It irritates the lining of the digestive tract, causing indigestion and intestinal bleeding, and it may also affect the liver. People with lupus, it appears, are more likely than most people to be prone to abnormal liver reactions to aspirin, especially in high doses, so the develop-POL text Q6 good.qxp 8/12/2006 7:39 PM Page 61

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ment of NSAIDs about forty years ago was welcomed by rheumatologists and arthritis sufferers alike.

NSAIDs suppress pain by interrupting the messages sent from the site of the pain to the brain. The cytokines—the chemical messengers that become so overexcited in rheumatic conditions—produce substances called
prostaglandins
that cause inflammation.

Aspirin and the NSAIDs work by interrupting this process. That’s why you will sometimes hear them called “prostaglandin inhibitors.”

When production of prostaglandins is reduced, so are pain, swelling, and stiffness. They are good as a first-line treatment for these symptoms because they are fast-acting (as anyone who is a fan of aspirin knows, it offers pain relief within half an hour). Inflammation and swelling take a little longer to be affected, but they start to go down within a week or so on a regular course of NSAIDs.

Just as experienced users learn that one painkiller works better for them than another, trial and error are usually required to find which NSAID is effective and produces the fewest side effects for individual lupus patients, because NSAIDs also have side effects.

The most common is indigestion, a result of the irritation the drug causes to the lining of the stomach, which can ultimately lead to ulcers. More refined versions that aim to reduce inflammation without damaging the gastric lining have recently been developed and are known as “coxibs” or “COX-2 inhibitors.” (To learn how these work and about their drawbacks, read the box “Good and Bad COX.”)

When NSAIDs are used to treat rheumatoid arthritis or lupus they are primarily being prescribed to reduce inflammation and thus are required in higher doses than for a headache or muscle strain.

Finding the right drug and establishing the effective dose with mini-mum side effects may take some time. Although these are for the most part tried and tested, garden-variety drugs, some of which are even obtainable without a prescription, in the doses used to treat arthritic symptoms they need close monitoring. In addition to the risk of a wide range of side effects, some people are allergic to them.

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Good and Bad COX

NSAIDs work by blocking an enzyme known as cyclooxygenase (COX), which contributes to the production of prostaglandins that in turn release platelets that promote blood clotting and protect the gut, kidneys, and blood. This is why prostaglandin-inhibiting drugs can damage the gut and kidneys, producing the common side effects of increased gastrointestinal bleeding and upset stomach. A little more than twelve years ago, scientists discovered that there were in fact two sorts of COX enzyme: COX-1, which acts to protect the gastric lining, and COX-2, which is only found in inflamed tissue and which is produced in response to stimulation by those overexcited cytokines that characterize autoimmune diseases. The race was on to inhibit COX-2—the bad guys—while leaving COX-1 to carry on the good work.

taking. Bottom line: Remember to always report any unusual symptom or reaction to your doctor right away. It is estimated that as many as thirty million people worldwide take NSAIDs every day to control pain and inflammation. Family doctors are familiar with their side effects.

There are currently four COX-2 inhibitors (coxibs) on the market (see the box “NSAIDs Used to Treat Lupus”), and two more are in the pipeline. At first there was much excitement about these improved NSAIDs; in clinical trials of people with arthritis they controlled pain and inflammation without as many nasty gastric side effects. However, in September 2004, follow-up research in a large number of patients revealed that there was a slightly increased risk of “cardiovascular events” (heart attack or stroke) for those on a coxib called rofecoxib or Vioxx, and the makers withdrew it.

Inevitably this raised questions about the others. The argument goes that normally, although COX-1 tends to promote thrombosis (blood clotting), it is inhibited by the action of COX-2, so that blocking COX-2 would suggest that unopposed COX-1 would indeed increase cardiovascular risk. On the other hand, inflammation is also implicated in cardiovascular events, and therefore controlling inflammation by blocking COX-2 should be protective. As POL text Q6 good.qxp 8/12/2006 7:39 PM Page 63

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NSAIDs Used to Treat Lupus

First, think for a moment about drug names. Drug names belong to no spoken language and are almost impossible for the layperson to pronounce or remember. They are assembled piecemeal by the people who develop the drugs and are intended to provide clues as to what’s in the medications or how they work. But drug names only do this for experienced pharmacologists. Just to complicate matters, each drug has at least two names: its chemical name, which describes its active ingredients, and its trade name or brand name, which, like Coca-Cola or Pepsi, is capitalized. Trade names are meant to be catchy and easier to pronounce than chemical names, but they often aren’t. And they vary from country to country, which makes them even more difficult to recognize.

There is an unspoken belief among doctors that patients don’t really need to know more about their drugs than is included in the patient information leaflet enclosed in the packaging (and which aptly carries the acronym PIL). They think it will make you worry.