Dr. Barry Dworkin » Prescription Drugs

Vioxx risk varies according to patient

Dr. Barry Dworkin — Wed, 24 Aug 2005 23:15:21 +0000

Originally published in The Ottawa Citizen August 24, 2005

What have we learned about the cardiovascular risk of Vioxx, with so much media attention lately? Health Canada set up a 13-member expert panel to review and critique the scientific evidence for the Cox-2 painkillers Vioxx, Celebrex and Bextra. The panel recommended in its July report that Merck could resubmit Vioxx for approval.

What were the reasons for this turnaround?

The non-steroidal anti inflammatory drugs (NSAIDs) have provided great relief for people suffering from arthritic and other painful conditions. Prior to the release of Cox-2 inhibitors, long-term NSAID use, especially in the aged, increased the risk of gastrointestinal bleeding and cardiovascular and kidney problems in susceptible individuals.

The Cox-2 inhibitors were promoted as a solution to the gastrointestinal bleeding complications. This was good news for people who required long-term symptom control.

The report released by the panel reviewed the scientific literature collected by the University of Oxford. The data included 138 clinical trials representing more than 144,000 patients. The panel concluded that most NSAIDs, including the Cox-2 inhibitors, share the same risk profile for the development of cardiovascular disease, high blood pressure and kidney disorders.

In a recent Sunday House Call interview on 580 CFRA, Dr. Arthur Bookman, associate professor of medicine at the University of Toronto, who is also president of the Canadian Rheumatology Association and a panelist on Health Canada’s expert advisory panel, said they reviewed every study of greater than one month duration that looked at a Cox-2 inhibitor versus a traditional anti-inflammatory drug such as diclofenac (Voltaren), naproxen (Naprosyn), ibuprofen (Advil, Motrin) or sugar pill (placebo).

They found that when the other Cox-2 inhibitors were compared to other NSAIDs such as diclofenac or ibuprofen, the heart attack risk rate was similar.

Yet studies indicated that Vioxx posed a greater risk of heart attack in older patients who had heart disease or a pre-existing risk of cardiovascular disease. Why was this result different from the other studies of Cox-2 inhibitors versus traditional NSAIDs?

In the analysis of the data, the panel discovered that ibuprofen (Advil, Motrin) had similar health risks. Indeed, ibuprofen was similar to Vioxx with respect to the increased risk of cardiovascular disease. However, Vioxx was pulled from the market because of claims that it was responsible for thousands of deaths.

“The reason Vioxx looked so bad,” explains Dr. Bookman, “is that it was compared with a traditional anti-inflammatory agent called naproxen. Naproxen has a protective effect and it seems to protect against heart attacks, not quite as good as Aspirin but it does protect against heart attacks.”

Dr. Bookman said that clinical trials comparing the Cox-2 inhibitors to sugar pills or placebo seemed to indicate the Cox-2 inhibitors were solely responsible for the increased heart attack rates. However, once the panel analysed the medical literature, both the Cox-2 inhibitor and the traditional anti-inflammatory drugs like ibuprofen and diclofenac were all increasing heart attack rates to similar degrees. “Naproxen was the only exception and it did not seem to increase heart attack rates,” said Dr. Bookman.

“The older you are, the more caution you have to exercise taking any type of anti-inflammatory,” says Dr. Bookman. “But if you have a risk of heart attack and that risk is high, then that risk is going to be increased with the traditional anti-inflammatory agents and with the Cox-2 inhibitors.

“So if you are a person who has had a previous heart attack, who smokes, who has a strong family history of heart attack, and who has a blood clotting problem, then you probably should not take an anti-inflammatory agent without careful consultation with your doctor.”

Almost all medications have side-effect risks. The benefits of the Vioxx and Celebrex as pain relievers outweigh the risks, according to the panel. It recommends that patients be provided more information on the labels and in the package insert.

Healthy people have an extremely low risk for adverse cardiovascular effects from all NSAIDs and Cox-2 inhibitors. The risk does increase with long-term use and in patients who are at risk of heart disease.

“Health Canada should consider that ibuprofen only be sold after discussion with a pharmacist, and must ensure that the risks of cardiovascular events are prominently displayed in materials that individuals receive at the time they purchase the drug,” says the panel report.

Great damage to the public trust occurs when the perception is that the review process fails to protect them from harm. Indeed, many health professionals depend on the review process to include all adverse reactions, benefits and risks.

The panel concurs and states that all information from all randomized trials should be available. Independent groups must have the opportunity to go through that same information and come to their own conclusions about the benefits and harms of these drugs.

It’s vital to know how drugs interact

Dr. Barry Dworkin — Tue, 30 Nov 2004 12:55:16 +0000

Originally published in The Ottawa Citizen November 30, 2004
Original Title is “Cytochromes: A Primer”

What is a drug interaction? Many believe it occurs when one or more medications directly affect the effectiveness of another. But how does it happen?

An understanding of the mechanisms that lead to this situation will enable the reader to ask a pharmacist pointed and specific questions about his or her prescription.

There are many seemingly random and chaotic lists of potential drug-drug interactions. Indeed, it can be an overwhelming proposition to try to list all of them.

Physicians, pharmacists and other health professionals need a logical evaluation of these interactions to sift out those that are clinically significant. To be clinically relevant, these interactions should be documented in humans, not animal studies.

For example, the blood-thinner warfarin (Coumadin) has to be consistently monitored and adjusted at times to maintain its anti-clotting effect. A drug that increases Coumadin blood levels can lead to an increased bleeding risk, and those that decrease blood levels increase the risk of a clot or stroke.

In this case, Coumadin has a narrow therapeutic range; dosing is incrementally adjusted over days to prevent wide swings in anti-clotting effect that could prove harmful to the patient.

Drugs can interact with four major body functions. They can alter how well drugs are absorbed by the intestine, change their breakdown and elimination rate (detoxification rate in the liver), reduce or increase the rate of excretion and elimination by the kidneys, and alter how well the drug spreads through the different body tissues and fluids.

Food and antacid use can delay intestinal absorption of medications. This is helpful especially for some medications that are absorbed too rapidly on an empty stomach; hence the recommendation to take with food.

Some antibiotics will eliminate some of the intestinal bacteria that will break down certain drugs such as digoxin, among others, possibly leading to toxic blood levels.

Why does grapefruit juice pose a problem? To understand this, a brief description of how the liver detoxifies the body is in order.

Most drugs are metabolized in the liver. Imagine the liver to be a giant biochemical processing factory. Within this huge factory, different departments specialize in processing specific drugs and toxins. Each department uses tools, designed to work on specific drugs, to complete its task.

The factory is called the Cytochrome P450 system. It is a complex mechanism that will use a variety of cytochrome enzymes (tools) to break down (metabolize) a variety of drugs. Indeed, a person’s genetic background can determine whether these cytochrome enzymes will be present in the liver.

Each of the cytochrome enzymes has a name that reflects its shape, structure and function; sort of like a set of wrenches and screwdriver bits.

If the enzyme is absent, the medication cannot be efficiently metabolized; people with this condition are termed poor metabolizers. It is as if that wrench and screwdriver set you bought at the hardware store to take apart that shelf is missing some sizes that you need; you now cannot dismantle it.

For example, one cytochrome called CYP2D6 is responsible for the breakdown of anti-depressants, codeine, statins (cholesterol medications) and beta blockers (used to treat hypertension). Five to 10 per cent of whites do not have this enzyme and thus cannot efficiently break down these drugs, whereas this occurs in less than one per cent in black and Asian populations.

These poor metabolizers can experience adverse side effects when given standard drug doses. Some people will not respond to codeine because they cannot metabolize and convert it to its active form, morphine, because they lack this cytochrome.

But genetics is only one way that someone becomes a poor metabolizer. Some medications and foods will block the activity of the enzyme, effectively deactivating it. Grapefruit is a prime example.

Grapefruit (juice) can affect a cytochrome called CYP3A for up to three days after ingestion. A standard dose of medications such as calcium channel blockers, among others, may result in a doubling of blood levels. This happens even if the grapefruit juice is ingested hours after dosing.

Indeed, grapefruit juice should not be part of the diet if someone is taking a medication metabolized by CYP3A.

Certain drugs can increase the rate of drug metabolism (drug breakdown). This process is called enzyme induction. Some patients will have to take a greater medication dose to achieve the same beneficial effect.

With your next prescription, your pharmacist or physician will be duly impressed when you ask them, “Does this medication affect the Cytochrome P450 system?” Even better, you will understand the answer.

Promising breast cancer treatment needs supporting studies

Dr. Barry Dworkin — Wed, 15 Oct 2003 21:04:31 +0000

Originally published in The Ottawa Citizen October 15, 2003

Original Title: A review of letrozole therapy for breast cancer

The announcement last week that Letrozole reduced breast cancer recurrence represents another step forward in the battle against breast cancer. When an announcement of a “groundbreaking” study, it is understandable to react with hope that a cherished life will be saved and suffering will end.

Methodical evaluation of new research and treatments is critical to provide the public and health care professionals accurate information. Indeed, it is especially important when dealing with common diseases that touch the lives of many families and friends. Television and radio news, because of time constraints, cannot cover all the details and critical analysis of each medical study.

It is necessary to digress for a moment to define two terms integral to providing perspective to study results. Most studies will report disease reduction in one or two ways: relative and absolute difference. It is these terms that can be a source of confusion and misunderstanding.

Suppose a disease incidence in a particular group was initially two per cent and after treatment was reduced to one per cent. One could conclude that the incidence was cut by 50 per cent ((2-1)/2). This is relative difference. Since the rate dropped from two to one per cent, the absolute difference is one per cent (2-1).

The well-designed letrozole produced clinically relevant information. Important limitations of the study need addressing to provide a balanced view of the results. Two editorials in the November 6, 2003 issue of the New England Journal of Medicine (NEJM) reviewed the data with a critical and supportive eye.

In any study, the sample size (study population) must be great enough to provide statistically significant results. The letrozole study met this criterion by enrolling 5187 women eclipsing the minimum statistical requirement of 4800.

The study evaluated post menopausal women over the age of 50 years with estrogen receptor sensitive breast cancer. Each had recently completed five continuous years of Tamoxifen therapy. The investigators wanted to know if Letrozole, introduced following Tamoxifen therapy, would reduce breast cancer recurrence compared to women who did not take letrozole (the placebo group).

The length of the study was to last five years. It was halted at 2.4 years because the reduction in breast cancer recurrence exceeded their expectations. It was decided that it would be unethical to withhold this treatment from the placebo group.

Of the 5157 women, 75 out of 2575 (2.9 per cent) in the Letrozole group and 132 of the 2582 women (5.1 per cent) in the placebo group had a recurrence of their breast cancer. In other words, 57 fewer women compared to placebo developed breast cancer. This result was reported as a 43 per cent relative reduction ((132-75)/132).

The absolute reduction of breast cancer is somewhat different. Indeed, Dr. Harold J. Burstein in a NEJM editorial states, “To date, letrozole has reduced the aggregate number of recurrences of breast cancers from 5.1 per cent to 2.9 percent-a reduction of approximately 1 event per 100 women treated per year.” The one in 100 statistic is calculated by dividing the absolute reduction of 2.2 per cent (2.2 women per 100 women) by 2.4 years.

The study presents other limitations. The investigators admit the lack of a true five-year duration makes it difficult to project the long-term consequences of letrozole treatment. At best the study’s conclusions reflect only two to three years of Letrozole treatment.

It is difficult to extrapolate the information past three years. Indeed, the stated objective of the trial was “to determine the disease-free survival and overall survival for women who has previously received = 5 years of adjuvant (tamoxifen) randomized to receive either letrozole 2.5 mg daily or placebo for five years.”

Overall survival was not significantly different after two years between the placebo and letrozole group. Extrapolation of the data into the third and fourth years indicates five to six per cent more women in the letrozole group would have survived.

John Bryant, Ph. D. and Dr. Norman Wolmark in their NEJM editorial comment that these findings cannot “be used to support a recommendation of five years of letrozole treatment, since none of the patients have been followed that long.”

They further state that the long term safety of this medication with respect to heart and bone health and quality of life could not be determined. Letrozole blocks the production of estrogen. It is associated with the development of osteoporosis, hot flashes, night sweats, muscle ache, arthritis, osteoporotic fractures, potential cardiovascular disease and impaired sexual function.

It is therefore difficult to make clinically appropriate judgments about the risks versus the benefits of the treatment when the full extent of its side effects and efficacy remains unknown.

As with other treatments, time, experience and more clinical trials will help answer some of the unknowns. Letrozole is an option for specific patients but they must be apprised of the limitations of the data. It is imperative that post menopausal women with estrogen receptor sensitive breast cancer discuss her options with her oncologist.

Safety with medication vital during pregnancy

Dr. Barry Dworkin — Tue, 19 Aug 2003 22:54:58 +0000

Originally published in The Ottawa Citizen August 19, 2003
Original Title: Medication safety during pregnancy

Moms-to-be should speak to their pharmacist and doctor about prescription medications and any other drugs they might be taking’ What medications are safe to use during pregnancy? Should I stop my prescription medications? How can I treat my heartburn? Can I drink coffee?”

Health care providers need accurate information to answer these questions. Some women have medical conditions that require ongoing treatment. If they stop, they could increase the potential risk to their baby and themselves.

Minor health problems might require medical therapy, and pregnant women may use over-the-counter medications (OTCs) to treat them.

There is understandable angst and concern about medication use during pregnancy. One or two per cent of birth defects are due to drug exposure during that time. Ninety five per cent of defects are due to random chance or genetics.

It is unethical to subject pregnant women to clinical trials to establish the safety of a particular medication. The risk to the fetus and mother outweigh any potential benefit of the research — a lesson learned from the use of thalidomide.

In 1975, the U.S. Food and Drug Administration defined pregnancy risk factors for all drugs, and Motherisk (www.motherisk.org) provides a similar service to the public and health care providers.

In June, the Centre for Addiction and Mental Health (CAMH) released a booklet called Is it Safe for My Baby? It offers assessment of risk and recommendations for the use of medication, alcohol, tobacco and other drugs during pregnancy and breastfeeding.

This excellent guide reviews the safety of more than 200 substances when pregnant or breastfeeding. It includes a host of information covering over-the-counter and prescription medications, illegal drugs, herbal preparations, cosmetics, household chemicals, solvents, paints and cleaners.

The booklet’s release comes at a time when some prescription-only medications are now reclassified as OTC medications.

Pregnancy is not a static situation. Certain medications might be safe in the last trimester but not in the first. The reverse is also true. Let us look at some common concerns during pregnancy: pain, heartburn, nausea, constipation, caffeine, tobacco, marijuana and herbal remedies.

Tylenol (acetaminophen) is present in many OTC cold and flu medications. There is no known link between it and birth defects. ASA-containing products such as Aspirin and non-steroidal anti-inflammatory (NSAID) medications seem to be safe in the first two trimesters of pregnancy but only in low doses. However, greater doses might cause bleeding in the newborn, decreased birth weight and prolonged pregnancy.

Therefore, ASA and NSAIDs should not be used in the last trimester (28 to 40 weeks).

Infrequent use of Tylenol with codeine or other prescription narcotics is safe, but daily use can increase the risk of miscarriage, premature delivery and complications during delivery. If possible, stick with acetaminophen alone to treat pain.

Heartburn can worsen as the size of the uterus increases. Increasing pressure within the abdominal cavity can cause stomach acid to splash up into the esophagus. Antacids such as Tums, Maalox, Rolaids and Gaviscon are generally safe to use throughout pregnancy. If these options fail, the use of Zantac or Pepcid would be the next safe step.

For nausea, Diclectin (pyridoxine/doxylamine) is the only medication approved by the Society of Obstetricians and Gynecologists of Canada for use during pregnancy. The society does not recommend Gravol (dimenhydrinate) for routine use, but it is used in its intravenous form for severe vomiting and dehydration (hyperemesis gravidarum).

Fibre laxatives such as Metamucil or Prodiem and stool softeners Soflax and Colace are safe to use. The stimulant laxatives such as Ex-Lax, cascara and castor oil might cause uterine contractions and should be a last resort.

Caffeine in excess of 300 milligrams per day (three regular cups of coffee) can increase the risk of miscarriage and low birth weight babies. Caffeine consumption in a combination of other products such as 500 millilitre energy drinks (50 to 125 milligrams), a 45-gram chocolate bar (50 milligrams), 355-millilitre colas (30 to 90 milligrams) and a cup of tea (20 to 90 milligrams) can easily exceed the maximum allowable daily limit.

The harm from tobacco is dose-dependent. The more you smoke, the greater the miscarriage risk, premature delivery and low birth weight babies. It is the carcinogenic compounds and other chemicals rather than the nicotine that increase the health risk to the fetus.

Cannabis (marijuana) poses the same risk to the fetus as tobacco with an extra caveat: Newborns might have more sleep disturbances and other cognitive difficulties.

While some clinical data exists for some herbal remedies, the effect of others remains unknown. Ginkgo biloba can cause bleeding, dong quai (ephedra) and feverfew can induce premature labour.

Discuss your concerns with your doctor or pharmacist before taking medication and review all your prescription medications during your pregnancy.

The information booklet is available from CAMH for $2.50 (1-800-661-1111 or by contacting marketing@camh.net).

© Dr. Barry Dworkin 2003

MDs, patients must adjust attitudes toward antibiotics

Dr. Barry Dworkin — Wed, 22 Jan 2003 02:18:23 +0000

Originally published in The Ottawa Citizen January 21, 2003
Original Title: So many bugs, so little time

Educational campaigns alerting physicians and the public about the dangers of indiscriminate prescribing and use of antibiotics is beginning to raise awareness of the problem. This is a worldwide health issue. In many developing countries, prescriptions are not a requirement to purchase antibiotics. In the West, the indiscriminate use of antibiotics in livestock and fish further complicates matters.

More than 40 per cent of all antibiotics are used as livestock growth promoters in animal feed on U.S. farms. This misuse of antibiotics promotes the development of resistant strains of bacteria poses a risk for the human population. The gradual discontinuation of antibiotic use in animals is a recommendation from a World Health Organization Panel.

What is bacterial resistance? Long-term exposure to the same antibiotic can cause some bacteria to change. Sometimes they accomplish this on their own accord. These changes can enhance the germ’s ability to defend itself against antibiotic attack. Increasingly, they are winning the fight. They can reproduce even while you are taking an antibiotic. This is what germs being “resistant” to an antibiotic mean.

The news reports talk of hospital superbugs, methicillin resistant Staphylococcus aureus (MRSA) and vancomycin resistant enterococcus (VRE), resistant to every available antibiotic. Although once the domain of hospitals, there is concern that these bugs will eventually end up in the community. Indeed, there are resistant strains of tuberculosis present in certain areas of North America.

We are virtually defenseless against these germs. There are few new antibiotics on the horizon to counter this threat. Are we to face the same helplessness and suffering that was so common prior to the advent of antibiotics in the 1940’s?

In 1998, the Workshop Report: Forum on Emerging Infections, Division of Health Sciences Policy, Institute of Medicine, Washington, D.C. estimated that 20 to 50 percent of antibiotic prescriptions prescribed by community primary care physicians in the United States were unnecessary. So too were 25 to 45 per cent of all U.S. hospital-based prescriptions.

The report urges primary care physicians to adjust their prescribing behaviors to ensure that the crisis does not worsen.

What have we learned about antibiotic resistance?

The longer the antibiotic use in the general population to treat a specific infection, the more likely resistance will appear.
Resistance progresses from low to high levels. The reverse is less likely to happen.
Once a microbe becomes resistant to one antibiotic, it often will do so again against another.
Antibiotic resistance will not disappear. It may slowly reverse itself with the cessation of indiscriminate use.
The antibiotic alters germs within a person’s body. These germs can spread to other people in the surrounding environment.

You and your doctor must work together in order to better control antibiotic resistance. Childhood vaccinations and routine boosters through adulthood reduce the risk of certain bacterial infections.

Physicians sometimes prescribe an antibiotic because of patient demand. Some insist they receive an antibiotic for their sore throat because their previous physician always prescribed one. This form of prescribing strengthens the patient’s belief that antibiotics treat all forms of sore throat. The expectation of an antibiotic prescription means that the patient is more likely to return to the doctor’s office for every sore throat.

The Workshop report recommends that physicians take the time to educate patients about antibiotic use. They state physicians prescribe antibiotics only if there is convincing medical evidence of a bacterial infection.

In family practice, it is common to encounter complaints of sore throat, cough, earache, sinus congestion and urinary bladder pain. These problems are not always bacterial in origin.

If the diagnosis of a bacterial cause for these infections is unclear, several tests can help the physician determine whether there is a need for antibiotics:

Send a throat swabs to the lab for a bacterial culture or perform a five-minute rapid Strep throat test in the office.
A chest x-ray can help diagnose pneumonia.
A one-minute simple urine test strip can diagnose a bladder infection.
Not all earaches and sinus congestion require antibiotics. Sometimes it is prudent to wait a day or two to monitor its progress before initially opting for antibiotic therapy.

In the event of a positive test, complete the full course of antibiotics in order to eradicate all the disease-causing bacteria. Stopping treatment at the mid-way mark encourages resistance among the few surviving bacteria.

Your doctor should take the time to explain why antibiotics are not used to treat viral infections. Most people want reassurance that their illness is not serious. Accurate information empowers patients to understand the nature of their illness. Many accept the explanation and learn from the experience.

Next week’s column will review the differences between bacteria and viruses. How do antibiotics work? Get your microscopes ready.

Medication only part of asthma care

Dr. Barry Dworkin — Tue, 12 Nov 2002 13:02:55 +0000

Originally published in The Ottawa Citizen November 12, 2002
Original Title: A Puff of Fresh Air

Part I – Be alert for early warning signs of asthma

Asthmatics can suddenly crash and burn. Last week’s column made note that asthma is an inherently unstable disease. Some patients unknowingly play with fire by ignoring the symptoms. A good web site to determine the risk of asthma in children and adults is found at http://allergy.mcg.edu/home.html.

Most physicians agree that aggressive treatment to stabilize and control asthma is a top priority. What approaches do physicians apply to prevent the serious consequences of asthma?

An initial patient history provides valuable information. Although medications are a mainstay of treatment, treating asthma is not just about prescribing them and wishing people well. The ultimate goal is a comprehensive approach that includes the minimum amount of medications to provide a maximum positive benefit.

An individualized approach includes determination of a history of allergies, sporting activities, smoking, medication use and work environment among other factors.

Removing asthma-triggering substances or optimizing protection from the elements or noxious substances is a helpful step. Indeed, piling on ever-increasing doses and types of medication to compensate for worsening asthma without determining its triggers misses an important aspect of care.

For arguments sake, assume that correcting for the above factors has not led to stable asthma control. The patient continues to suffer from his or her asthma. The choice of medication follows a rational stepwise approach.

The goal of asthma treatment is to reduce the inflammation and airflow resistance of the airways to improve lung function. The choice of medication depends on the severity of the illness.

Short-acting bronchodilators, usually packaged in blue-coloured inhaler delivery systems, include salbutamol, found in Ventolin, Apo-Salvent and Airomir, Bricanyl (turbutaline), Berotec (fenoterol) and Atrovent (ipatropium bromide). In very young children, liquid Alupent (orciprenaline) may be used to help diagnose Asthma prior to the use of inhalers. These fast-acting agents relax the smooth muscle bands around the airway. The diameter of the airway increases making it easier to breathe.

Bronchodilators can cause jitteriness and a temporary increase in heart rate. This usually subsides within ten to 20 minutes. Overuse of these medications can render them less effective.

Longer acting bronchodilators (turquoise packaging), Oxeze (formoterol) and Serevent (salmeterol), last up to eight to 12 hours between doses. They remain effective with long-term use.

The anti-inflammatory agents (inhaled steroids) are the key to treating asthma. They shrink the swollen inner walls of the airways curtailing mucous secretion and blockage. These medications (brown or orange packaging) include Flovent (fluticasone), Pulmicort (budesonide), Q-Var and Becloforte (Beclomethasone). A non-steroid formulation, Tilade, is available but is not commonly used for compliance and taste reasons.

Long-term studies indicate that there is little to no growth suppression in children who use them. They provide excellent asthma control. The most common side effects of inhaled steroids are a hoarse voice and oral thrush. Rinsing and gargling immediately after use reduces this risk.

Two combination inhalers, Advair (Serevent and Flovent) and Symbicort (Pulmicort and Oxeze) can improve overall asthma control.

Leukotriene inhibitors (Singulair and Accolate) block a specific biochemical pathway related to a delayed allergic response that stimulates inflammation. They are an adjunct to the standard asthma medications and tend to work better for people with exercise-induced asthma. A daily tablet for some people may reduce their daily dose of inhaled steroids.

For severe asthma exacerbations, oral or intravenous prednisone may be required. Prednisone, a steroid, rapidly reduces inflammation over 12 to 24 hours. It is used when asthma does not respond to the usual treatment regimen or the patient is temporarily unable to inhale their medication. The severity of the asthma exacerbation dictates whether the patient ends up at home or in hospital.

Asthmatics can have different symptoms. Those that wheeze and cough only while participating in aerobic activities have treatment that differs from someone who has symptoms at any time of the day or night. The bottom line is to prevent the progression of the disease. Some, as they age, will suffer fewer attacks while others have it for life.

Many people do not correctly use their inhalers. The proper technique is critical to successful therapy. These patients usually conclude that the medication did not work when in fact little medication reached the lungs. Your doctor, public health nurse or respiratory technician can show you how to use them.

Bronchodilator use more than two to three times per week indicates poor asthma control. Asthmatics experience more bouts of pneumonia, colds and flu. Some cannot keep up with the physical demands of their job or sport. There are Olympic athletes that depend on their asthma medications in order to compete.

Some asthmatics continue to smoke. Their asthma attacks become progressively more severe and frequent. In my practice, several wonderful patients continue to deteriorate. Each asthma attack is worse than the last. I fear they will soon succumb to their asthma if they do not quit smoking.

There is a tendency to experience our illnesses from an individual perspective. In fact, most illnesses affect the entire family. As difficult as it is to quit smoking, the challenge is to stay alive to see your children grow up. Consult with your doctor and do what you must to succeed, for everyone’s sake.

Elderly suffer after lengthy use of anxiety drugs

Dr. Barry Dworkin — Tue, 23 Apr 2002 22:10:43 +0000

Originally published in The Ottawa Citizen April 23, 2002
Original Title: Around the Benz

Mr. T. is a strapping 85 year-old man who suffers with an anxiety disorder. He also cares for his wife who is severely affected by Alzheimer’s. Twenty years ago he was prescribed clonazepam (Rivotril), a benzodiazepine (BDZ). He became dependent upon them to control his anxiety. BDZs and the elderly do not mix well.

Benzodiazepines such as Alprazolam (Xanax), oxazepam (Serax), diazepam (Valium), Rivotril and lorazepam (Ativan) are widely prescribed medications. They are used for the immediate treatment of seizures and convulsions, detoxification from alcohol, muscle spasms, pre-surgical sedation, insomnia and most commonly for anxiety related disorders and conditions. Some people use them for jet lag use or if they have an air travel phobia.

Perusing the product monographs found in the Compendium of Pharmaceutical and Specialties (CPS), the big blue tome in your doctor’s office, benzodiazepines are not indicated for long-term use. Approximately 15 percent of the adult population has taken a BDZ one or more times over the past year. One to two percent has taken them daily Mr. T. is a strapping 85 year-old man who suffers with an anxiety disorder. He also cares for his wife who is severely affected by Alzheimer’s. Twenty years ago he was prescribed clonazepam (Rivotril), a benzodiazepine (BDZ). He became dependent upon them to control his anxiety. BDZs and the elderly do not mix well.

Perusing the product monographs found in the Compendium of Pharmaceutical and Specialties (CPS), the big blue tome in your doctor’s office, benzodiazepines are not indicated for long-term use. Approximately 15 percent of the adult population has taken a BDZ one or more times over the past year. One to two percent has taken them daily for 12 months or longer. Some patients have been using them for decades. The elderly are major consumers of this medication.

Patients prefer them because of their rapid onset of action and that they can be used on an “as needed” basis. They are problematic medications because of their abuse potential and effect on concentration, driving and balance. Long-term daily use over months and years can lead to habituation, dependency and tolerance (needing increasing doses to produce the same effect).

They are responsible for confusion and poor balance especially upon awakening in the middle of the night as many elderly people are wont to do. They have an increased risk of falling that can unfortunately lead to broken hips, internal bleeding and head injuries. Driving the following day is statistically hazardous (doubling the risk of a crash) even after the sedating effects of the medication have waned. Reaction times and reflexes are diminished. This is true for young and old drivers alike.

BDZs are particularly damaging to the sleep cycle. The normal sleep cycle has four stages (1 – 4) plus a dream stage (REM sleep). The first two stages are associated with light sleep followed by the deeper more restful third and fourth stages. We all know these stages quite well. When roused from deep sleep we have that “hung- over” feeling whereas awakening from light sleep is a mere nuisance. Benzodiazepines increase the time spent in stage one sleep and interfere with the deep stages. Although you will sleep, it is not refreshing. Sleep cycles can be damaged by their long-term use. This is another reason why people have such a difficult time stopping BDZs. They become dependent upon them to induce sleep since their brain is now unable to do so independently.

Newer non-addictive medications are available to help people with insomnia such as Zaleplon (Starnoc) and Zopiclone (Imovane). Starnoc helps you fall asleep. Imovane reduces the duration of light sleep but increases the time spent in deep sleep thus preserving sleep architecture (the normal sleep cycle).

Although effective for acute (sudden) anxiety, BDZs do nothing to treat the underlying cause of anxiety disorders. These disorders are interrelated with Major Depressive, Obsessive-Compulsive, Generalized Anxiety and Panic Disorders. All these conditions are treated with non-addictive medications that treat the disease and not the symptoms. Anxiety usually wanes once the underlying cause is treated.

There specific indications for BDZ use. Most physicians do not like to prescribe them especially when other alternatives are available. The problem: Starnoc and Imovane are not covered under the Ontario Drug Benefit program. This leaves many patients and physicians unable to choose this option. Many elderly patients do not have supplementary health insurance. The group most at risk is yet again penalized. Score another point for the short-sighted bureaucrats at the Ministry of Health.

BDZs are relatively contraindicated in patients with current alcohol and drug abuse problems and for those in recovery programs. They should never be used during pregnancy because of the risk of birth defects. It can lead to dependence and withdrawal symptoms in the newborn. Patients addicted to BDZs are advised not to abruptly stop their medication because it can lead to seizures. Withdrawal has to be done slowly and under the direct management and close supervision of a physician.

Mr. T. switched to an anti-depressant medication. Over the course of five weeks he gradually reduced his clonazepam dose until he was able to completely stop. His anxiety has disappeared and my anxiety about a potential disaster abated. He is better able to care for his wife.

If you have concerns about this issue talk to your doctor. If warranted, seek alternative solutions to your problem. And get a good night’s sleep.

This Drug’s For You

Dr. Barry Dworkin — Tue, 11 Dec 2001 12:49:51 +0000

Originally published in The Ottawa Citizen December 11, 2001

In Ontario there are two drug programs designed to reduce the burden of medication costs: The Ontario Drug Benefit Program (ODB) and the Trillium Drug Program (TDP). The ODB covers the cost of medications for seniors, welfare recipients and the disabled. The TDP, a co-payment plan varies with an individual’s or family’s income.

Within the ODB there is a substantial list of medications that require the use of the Limited Use form. As the name implies, “Limited Use” is designed to control the use of newer more expensive medications. A patient becomes eligible to receive these medications if they “qualify” for them. Another component is the Section 8 reserved for medications covered only if it is critical to the patient’s survival. Bureaucrats decide on the use criteria. It frequently drives both physician and patient to frustration.

For example, Avandia and Actos are new medications used in the treatment of Type 2 (non insulin dependent) diabetes. They too are designed to control blood sugar but also have the advantage of promoting kidney protection, heart disease risk reduction and improved cholesterol profiles. Some patients are able to reduce the dose of their other diabetes medications. With early use especially in the younger diabetic, the risk of the diabetic complications can be reduced. However, these are Section 8 medications. Unless the patient has failed to have their blood sugar controlled with the other available medications, the cost will not be covered.

For the treatment of osteoporosis only one drug is covered: Didrocal. It maintains bone density in the hip and spine. More efficacious “Limited Use” medications like Fosamax or Actonel are available but cannot be used until there is proof that Didrocal was ineffective. If, while using Didrocal, you suffer a new osteoporosis fracture after a year or your bone mineral density has decreases by more than three percent over two years or you experience intractable side effects, then you can be prescribed Fosamax or Actonel.

Fracture repair and rehabilitation costs more than the medication. Consider the suffering and affect on quality of life. Hip fractures in the elderly can be fatal. Physicians are in the business of providing the best possible care for their patients. It is frustrating when there is a better medication for your patient but you cannot prescribe it. People have to experience uncomfortable side effects, suffer a grievous injury or demonstrate that the medication is ineffective before being eligible for coverage.

The issue is long term versus short term cost savings. We are aware of the increasing utilization of hospital-based care. Is it not better to invest in treatments that can potentially reduce future utilization? If we can keep someone away from diabetes-induced kidney disease, dialysis, heart disease, heart attack and amputation, is it not in everyone’s best interest to invest in their continued well being?

The cost of developing a new medication varies between 500 million and one billion dollars. On average one new drug is developed for every 5000 tested. It takes about ten years to bring a drug to market. Pharmaceutical companies must have a return on their investment but not to abuse their position. Why is there great cost disparity between the United States, Canada and Latin America for the same medications? Should not pricing be standardized worldwide? As much as I support the efforts of our pharmaceutical companies, they must be reasonable. What is an acceptable return on their investment? There has to be a balance between profits and humanitarianism. Despite popular belief, doctors are in cahoots with pharmaceutical companies. Most of us treat patients with medications that we ourselves would use under similar circumstances. Sometimes that involves prescribing a more expensive non-covered medication.

As it stands our healthcare system unsustainable. By 2020, Ontario’s elderly population will increase by 70% while the total population will increase by 25%. We cannot afford to cover the total cost of these medications. We can choose to use less expensive drugs for our health problems or opt to choose newer and perhaps more efficacious treatments but pay for them.

In Quebec, patients have a co-payment plan wherein the government covers the basic cost of medications and the patient pays the difference. A sliding scale based on income could reduce the burden for those less capable of paying for their medications.

The definition of who qualifies for complete coverage will have to change. It is not a palatable choice but we are forced to consider it. The sooner that government admits that it cannot afford the current healthcare system the better. Expecting governments to pay for everything is not an option anymore. It means applying for supplemental medication insurance with government providing coverage for the inexpensive basics. Those that can afford insurance can reduce the burden on the system so we can help the less fortunate. We have to be proactive, responsible and not wait for bureaucrats to fix it.