Dr. Barry Dworkin » Toxicology

A headline’s tale of two flu stories: Reality vs deliberate misrepresentation of risk

Dr. Barry Dworkin — Sat, 17 Oct 2009 22:03:26 +0000

I am not a fan of how newspapers use headlines to misrepresent stories to provke unwarranted fear, and heightened risk perception. Today, the Ottawa Citizen published two stories about seasonal and H1N1 vaccine. The first story, For Guillain-Barre survivors, flu shot stirs up unwelcome memories, emblazoned on the front page has all the elements of what is regrettably become the norm in newspaper headlines. Headlines are not under control of the journalist. The article was written by Sharon Kirkey.

Ottawa Citizen journalist Dan Gardner’s book, Risk: The Science and Politics of Fear discusses this journalistic approach to sensationalizing news called the Example Rule.

This rule is used to present rare occurrences as if they are common or lurking among us, misrepresenting true risk. Therefore, it was no great surprise to read the front-page headline of today’s Ottawa Citizen continuing this tradition. It outlines the history of a woman who develops a rare neurodegenerative disease called Guillain Barre Syndrome (GBS) and implies a link to the flu vaccine.

The medical content of the story accurately presented the risks of developing GBS, about 1-2 per 100, 000 people. There is some evidence that indicates that the flu vaccine may add an extra 1 per 1 million people. However, the headline clearly did not reflect this. It cites one Ontario study that the seasonal flu vaccine increases the relative risk of contracting GBS by 45 percent.

The absolute risk change of the 1 in a million increase was mentioned immediately following the 45 per cent claim. This former should have been the only statistic cited.

Relative risk is presented to emphasize dramatic change. It is used by media, pharmaceutical companies, food manufacturers, and the Natural Health industry among others to bolster their health claims.

Relative risk does not provide context for the change in risk and should not be included in health reporting. However, it is the number that will be cited by the reader when they discuss this issue with others, hence the problem of skewed risk perception.

The story ends with the woman who had GBS stating, “I made a promise to myself, that if I ever walk again, I will do whatever it takes to keep whatever doesn’t belong in my body out of it.” Although it is understood that traumatic experiences can influence one’s sense of risk, the statement is used to conjure up the idea that unnatural substances are implicated in the disease process and are to be avoided.

If that were the case, one could argue that we should avoid touching any manufactured product, walking down the street and being exposed to car exhaust’s polyaromatic hydrocarbons, and using chemical cleanser’s and agents among others. Exposure to some of these potentially harmful compounds is likely in the parts per million or billion as well. We do not routinely think about this because our sense of risk from these everyday products and activities is low.

News reporting should present information with context. The public should be treated with respect, which includes removing the fear mongering for the sake of selling newspapers, TV and radio shows and magazines. Globe and Mail health reporter Andre Picard has commented on this issue as well as Dr. Noni MacDoanald in an article written for the Canadian Medical Association Journal.

The second story written by Pauline Tam, Our best shot against swine flu?, deserves kudos to the reporter for excellent evidenced-based content and science writing.

Ms. Tam accurately represented the uncertainty that is inherent in medical research yet clearly emphasized the strength of evidence against many misperceptions about the flu vaccine.

She covered the issue about adjuvants or immune system boosters and reviewed how the adjuvant improves efficacy of the vaccine. The adjuvant, squalene, is produced by our liver and is found in many foods as natural oil.

One wonders why, given the focus by some groups on how natural products are better than synthetic, there is such controversy. It would make sense that the logic should remain consistent.

Ms. Tam also reviews the preservative thimerosal found in some multidose vaccines and cites evidence from numerous reputable sources regarding its safety profile.

What Ms. Tam accomplished it to foster critical analysis of health information and present it in context allowing the reader to make an informed decision and risk assessment. She shows medical research is always evolving and is not perfect (nor should it ever be if we are to continue to learn) and how it is a jigsaw puzzle of information pieces that are brought together to create the best picture to date about flu vaccine efficacy and indication for use.

Background:

The evidence-based website Up to Date cites this data:

Vaccination — Guillain-Barré syndrome has followed vaccinations, but this danger may be overstated.

Influenza vaccination — In the United States, an increased risk of GBS was associated with the swine influenza vaccine in 1976, although the severity of the risk has been controversial. Subsequently, no increased risk was observed up to 1991.

Individuals who received either the 1992-1993 or 1993-1994 influenza vaccinations were not at significantly increased risk for GBS, but combining the two seasons suggested that influenza vaccination resulted in approximately one additional case of GBS per million patients inoculated. This risk appears to be substantially less than the overall health risk posed by naturally occurring influenza.

The annual reporting rate of GBS following influenza vaccination in adults declined significantly from 1996-1997 through 2002-2003 in the US. Nevertheless, the long onset interval for post vaccination GBS compared with other post vaccination adverse events (median 13 days versus one day, respectively) is consistent with a possible causal association between GBS and influenza vaccine.

Other data are conflicting, but suggest that influenza vaccination is associated with a low or negligible risk of GBS. In a self-matched case control series from Ontario, Canada that identified 269 hospital admissions for GBS diagnosed within 42 weeks of receiving influenza vaccination, the estimated relative incidence of GBS during the primary risk interval (weeks two through seven after vaccination) compared with the control interval (weeks 20 through 43) was 1.45 (95% CI 1.05-1.99). However, a separate time-series analysis of 2173 hospitalized cases of GBS showed no statistically significant increase in hospitalizations for GBS after institution of the universal influenza vaccination program in 2000.

References:

Guillain-Barre syndrome following influenza vaccination.
Haber P; DeStefano F; Angulo FJ; Iskander J; Shadomy SV; Weintraub E; Chen RT
JAMA 2004 Nov 24;292(20):2478-81.

The Guillain-Barre syndrome.
Ropper AH
N Engl J Med 1992 Apr 23;326(17):1130-6

Guillain-Barre syndrome after influenza vaccination in adults: a population-based study.
Juurlink DN; Stukel TA; Kwong J; Kopp A; McGeer A; Upshur RE; Manuel DG; Moineddin R; Wilson K
Arch Intern Med. 2006 Nov 13;166(20):2217-21.

The Guillain-Barre syndrome and the 1992-1993 and 1993-1994 influenza vaccines.
Lasky T; Terracciano GJ; Magder L; Koski CL; Ballesteros M; Nash D; Clark S; Haber P; Stolley PD; Schonberger LB; Chen RT
N Engl J Med 1998 Dec 17;339(25):1797-802.

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.

Club Drug Use Carries Uncertain Risks

Dr. Barry Dworkin — Tue, 26 Apr 2005 03:29:58 +0000

Originally published in The Ottawa Citizen April 25, 2005
Original Title: Three More Members of the Club

Part One
Final of two parts

When discussing the potential side effects of drugs, risks must be viewed within a realistic context. Indeed, my last column on Ecstasy, or MDMA, and today’s on GHB (gamma-hydroxybutyrate), Rohypnol (flunitrazepam) and ketamine, contain information that is factually correct.

Each person reacts differently to the effects of a drug.

GHB, developed in 1960 by the French as an anesthetic, is a salty powder that is dissolved in water. It is manufactured from common industrial chemicals that can be purchased with home-production instruction manuals from websites.

It is structurally similar to a naturally occurring central nervous system transmitter, gamma-aminobutyric acid (GABA). GABA is believed to regulate sleep cycles, body temperature, memory and brain glucose levels. Its unpleasant salty or soapy taste can be masked by mixing it in flavoured or alcoholic drinks.

GHB’s effects are dose-dependent. The initial euphoria occurs about 15 to 30 minutes after ingestion, reaching a peak in 20 to 60 minutes. This effect can be tempered if taken with food. The use of alcohol or other central nervous system depressants can increase GHB’s potential toxic effects. The drug’s concentration within the powder is not known, increasing the risk of overdose.

The signs and symptoms of GHB intake that can precede overdose are dizziness, increased salivation, muscle relaxation and amnesia. There is evidence to suggest that as the level of consciousness wanes, the risk of a slower heart rate (bradycardia) and low body temperature (hypothermia) increases. Overdose might lead to abnormal and ineffective breathing patterns, seizures, coma and death. Recognition of the early signs and symptoms can help prevent this outcome.

Long-term regular users of GHB might develop drug dependence. The withdrawal syndrome can include insomnia, tremors and anxiety.

The drug Rohypnol, also known as the date-rape drug, is the same class of medication as Valium: It is a potent benzodiazepine. This prescription drug is available in many European and Latin American countries for use as a preoperative anesthetic, sedation, and as a treatment for insomnia. Being a prescription drug, there is quality control in its manufacturing process.

Rohypnol can induce sleep (hypnotic), reduce stress, inhibition and anxiety through sedation, and is a muscle relaxant at doses of one to two milligrams. The onset of action is about 30 minutes after ingestion, with a peak effect occurring after two hours. The drug’s effect can last up to 12 hours.

Exceeding the recommended dose can lead to loss of memory of events occurring from the time of ingestion onward (anterograde amnesia), lack of muscle control and loss of consciousness. Users who consume alcohol can increase the drug’s effect.

Depending on the dose and other concurrent drug use, some users can develop low blood pressure, confusion, dizziness, aggressive behaviour, urinary retention (inability to urinate) and visual disturbances.

Benzodiazepines are not usually recommended for long-term use because of the high risk of drug dependence. Some prescription benzodiazepines can cause dependence with two to three weeks of daily use. Withdrawal must be medically supervised in order to prevent seizures.

Ketamine is a derivative of phencyclidine (PCP). It prevents brain cells (neurons) to reclaim various neurotransmitter compounds that are released by one neuron to communicate with another. The neurotransmitter levels can build up and overstimulate certain brain areas. This effect can cause hallucinations and strange thoughts and ideations.

Ketamine is difficult to produce in a home lab because it requires a specialized manufacturing process. Most of the supply is taken from veterinary and human anesthesia products. Pharmaceutical grade ketamine comes as a liquid that can be swallowed or injected. Club users will allow the liquid to evaporate in order to collect the powder. The powder can be mixed with tobacco or cannabis and smoked or snorted.

Ketamine has a rapid onset of action that lasts 30 to 45 minutes. It can cause a dreamlike state or a feeling of floating outside the body. Increasing doses can lead to confusion, anterograde amnesia and delirium. Depending on the dose, other drug and alcohol ingestion and the person’s ability to metabolize the drug(s), some can develop hypertension, rapid heart rate (tachycardia), palpitations, a reduction in breathing effort (respiratory depression) with periods of apnea (no breathing).

Chronic users can become addicted. Withdrawal can be severe and require medical supervision to assist in the detoxification process.

The purpose of this series was to provide information about what is known about these drugs and not to be interpreted as scaremongering.

Information should be provided within a frame of reference or context that provides the reader with a means to gauge true risk. To wit, some users will not experience the severe side effects of club drugs; others will.

More research is required to provide people with an accurate assessment of their chances of experiencing these harmful effects. Until then, the user is travelling through uncertain risk territory.

The Club of Tortured Souls

Dr. Barry Dworkin — Tue, 05 Apr 2005 03:27:11 +0000

Originally published in The Ottawa Citizen April4, 2005

First of two parts

Recently, one of my patients with bipolar disorder took Ecstasy at a rave. Within 60 minutes she had collapsed on the dance floor from dehydration.

After a thorough assessment in the emergency room, she was given intravenous fluid replacement and sent home. The following day she came to my office for a follow-up visit, experiencing a precipitous decline in her mood.

This two-part series will look at four commonly used club drugs: Ecstasy (3,4-methylenedioxymethamphetamine or MDMA), GHB (gamma-hydroxybutyrate), Rohypnol or the date-rape drug (flunitrazepam), and ketamine. How do these drugs work and what are the health risks?

The club drugs stimulate the release of the neurotransmitters serotonin, norepinephrine and dopamine from brain cells. These neurotransmitters are intimately involved with mood stability. People use club drugs to enhance social interaction: They feel less inhibited and experience increased empathy, physical closeness and euphoria.

MDMA is the drug of choice at a majority of raves. It is an amphetamine derivative originally developed in 1914 for use as an appetite suppressant, but it never got past animal testing. Its chemical structure is similar to the hallucinogen mescaline. MDMA is addictive but less so than amphetamine, and it does not cause psychosis as often as LSD or other hallucinogens.

Many of the illicitly manufactured MDMA tablets are not pharmaceutical grade. They can contain “binders” or extra ingredients such as caffeine, dextromethorphan (cough suppressant), pseudoephedrine (decongestant), or hallucinogens like LSD or other potent amphetamine derivatives. The latter two ingredients in combination with MDMA can have strong unpleasant hallucinogenic effects.

MDMA’s effects occur 30 to 60 minutes after ingestion, faster if it is crushed or if its powder form is snorted. The effects can last up to eight hours. Serotonin, dopamine and norepinephrine flood the synapses or spaces between the nerve cells. This effect is enhanced by MDMA’s ability to block a brain enzyme that breaks down these neurotransmitters.

The euphoria occurs after a brief feeling of agitation, time disorientation, lack of appetite and reduced thirst. Some people may experience a mildly locked jaw (trismus) or will grind their teeth (bruxism). Both of these side effects can be tempered by sucking on a lollipop.

The overstimulation of the brain and central nervous system can lead to a serious life-threatening condition. The heart rate and blood pressure can increase above acceptable limits. Some users will experience tremors, seizures, clinically significant irregular heart beat (arrythmias), parkinsonism, esophoria (the eyes turn inward — cross-eyed) and an inability to urinate (urinary retention).

The most serious side effect of MDMA ingestion is an elevated core body temperature (hyperthermia) due to serotonin syndrome. This syndrome can lead to muscle rigidity and seizures, muscle breakdown (rhabdomyolysis), acute kidney and liver failure, adult respiratory distress syndrome, and blood clotting abnormalities.

MDMA also stimulates the pituitary gland in the brain to release antidiuretic hormone (ADH). This hormone will reduce the kidneys’ ability to produce urine in response to an increased fluid load; they cannot excrete water into the bladder.

This creates a ‘perfect storm’ of pathology. The body overheats from dancing and the effects of the drug. The kidneys shut down. The user will dramatically increase his or her intake of water and other fluids in response to increased body temperature. Without the kidney’s ability to excrete water, the fluid overload reduces the blood sodium concentration (hyponatremia) through dilution. Low sodium concentration levels coupled with high body temperatures can cause confusion, delirium, paranoia, headache, anorexia, depression, insomnia, irritability, and a rapid, involuntary, oscillatory motion of the eyeball (nystagmus), all of which may continue for several weeks.

Several days after using ecstasy, the effects of serotonin depletion can cause depression, and for some it is severe. People who repeatedly use MDMA increase their risk of cognitive deficits and potentially permanent memory impairment.

MDMA does change the brain’s normal function. Indeed, studies indicate that long-term use in typical recreational doses can lead to a paranoid psychosis that cannot in practice be distinguished from schizophrenia. Prolonged drug abstention will lead to a reversal of the psychosis.

There are some animal and human studies that indicate that MDMA use (possibly in conjunction with cannabis) can lead to cognitive decline in otherwise healthy young people.

My patient with bipolar disorder experienced a precipitous decline in mood because the MDMA depleted the serotonin stores in her brain. People with mental illness are more vulnerable to the deleterious effects of MDMA and other club drugs. It is akin to a patient with asthma or chronic lung disease who smokes. They will tend to have more severe disease and attacks than someone who does not smoke.

These drugs are adulterated with other chemical additives and, although most club drugs look like prescription medicines, they are illegally made and can cause harm even in small doses.

I will return to the club in my next column to review GHB, Rohypnol and ketamine.

Southern Exposure: Day of the Tentacle

Dr. Barry Dworkin — Sat, 12 Mar 2005 03:21:30 +0000

Originally published in The Ottawa Citizen March 11, 2005

The thrill of the winter sojourn to warmer climes and ocean activities like scuba diving, surfing and snorkeling, among others, can lead many to overlook other notable health and safety precautions.

If you’re heading south for some fun in the surf, remember the ocean is an alien world with creatures that, for all their beauty, can be a literal shock to the system.

What do you do when stung by a jellyfish, step on a sea urchin’s spine, encounter the whip of a stingray’s tail, or eat a poisonous fish?

Certain reef fish like grouper, king mackerel, sturgeon and snapper can ingest microscopic organisms called dinoflagellates either directly or by eating smaller fish. One particular species, gambierdiscus toxicus, produces a toxin that becomes increasingly concentrated as it travels up the food chain.

Thousands of people eating these fish found around Hawaii, Florida, Puerto Rico and the U.S. Virgin Islands can develop Ciguatera (seeg-wha-terra) poisoning. The severity of poisoning depends on the fish size and the number of exposures. The classic symptom found in 80 per cent of patients is a cold sensation reversal, where hot sensations are perceived as cold and vice versa.

Gastrointestinal and neurological symptoms usually begin one to six hours after ingestion and last seven to 14 days, and in some cases months to years. They include nausea, vomiting, watery diarrhea, abdominal pain, numbness, vertigo, severe weakness, muscle aches, slowed heart rate (bradycardia), low blood pressure (hypotension), diffuse pain and decreased vibration and pain sensations.

There is no immediate cure, only symptom relief. Cooking, freezing, salting or smoking the fish does not deactivate the toxin. If these fish are eaten, avoiding eating the fish’s internal organs like the liver because the toxin concentrates in these areas.

Travellers to Hawaii and California who eat tuna or mackerel may develop scombroid. Poor handling and refrigeration of the fish can cause a buildup of histamine and histamine-like substances within the dark meat. The person develops symptoms 30 minutes after ingestion. Symptoms can last about eight hours and include flushing, nausea, vomiting, diarrhea, severe headache, palpitations, abdominal cramping, dizziness, dry mouth, hives, and red eyes.

Treatment includes the use of antihistamines administered by mouth, intravenous or into the muscle, depending on symptom severity.

Encounters with jellyfish are memorable. Their long tentacles have stinging cells, or nematocysts, that sting. Nematocysts found on amputated tentacles and dead jellyfish will sting as well.

Symptom severity depends on the number of stinging nematocysts, the toxicity of the venom and each person’s unique reaction. The poison is destructive; it damages skin, red blood cells, heart tissue and nerves.

The most common symptom is local pain followed (in order or likelihood) by a “pins and needles” feeling (paresthesias), nausea, headache, chills and, rarely, cardiovascular collapse or shock. Symptoms can last up to three days.

Treatment focuses on pain relief and controlling neurologic symptoms. Use gloves or forceps to remove any visible tentacles. Avoid touching towels used to wipe off the nematocysts; they will sting. A 30-minute application of vinegar (five per cent acetic acid) will stop any remaining nematocysts on the skin from releasing their venom. Salt water is a good substitute if vinegar is unavailable. Never use fresh water because it will stimulate venom release.

Scraping the nematocysts off the skin using shaving cream and a razor is another solution. There are reports that cold and hot packs can help sooth the pain.

Stepping on a sea urchins’ toxin-coated spines will cause pain and burning and occasional skin discolouration lasting about 48 hours. The spines will break if you try to remove them by hand. Fragments will remain embedded in the skin and can cause infection. Surgical removal and wound debridement may be necessary.

The stingray’s venomous spine is at the end of its tail. The venom will reduce blood flow to the affected limb causing tissue death and destruction, poor wound healing and infection.

Intense pain is immediate and can be accompanied by salivation, nausea, vomiting, diarrhea, muscle cramps, shortness of breath, seizures, headaches, muscle cramp and cardiac arrhythmias. Fatalities are rare.

Bleeding from the puncture site is controlled by direct pressure to the wound. Hot water soaks will help reduce the pain.

Wound care includes thorough rinsing of the affected area with fresh water. Patients should check for redness and swelling at the site; a sign of infection. Sometimes, part of the spine will remain embedded in the tissue; surgical removal may be necessary.

A tetanus shot may be required for stingray and sea urchin stings. Although fatalities are rare for all these toxic reactions, prompt recognition of the symptoms can lessen the discomfort and morbidity.

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.

Herbal remedies can work, but they are not always safe

Dr. Barry Dworkin — Tue, 02 Sep 2003 12:34:59 +0000

Originally published in The Ottawa Citizen September 2, 2003
Original Title: Eau Naturelle

Herbal remedies are medical concern. A substantial minority of people use them. Indeed, many people do not tell their doctor about herbal medication use unless directly asked. This is not a recipe for good comprehensive health assessment. Some herbal preparations will adversely interact with prescription medications.

At times, there may be an automatic dismissive response on the part of physicians should patients bring up the topic of herbal treatment options. This reaction comes in part from the outrageous claims (without supportive evidence) for some of these remedies. Some herbals list a multitude of unrelated diseases. Claims for Echinacea, for example, include using it to treat acne, strep throat, gonorrhea and even typhoid fever.

There is a saying, “Extraordinary claims require extraordinary evidence”. Physicians face the overwhelming task of trying to explain why the herbal/drug does not work for a particular condition(s) in five minutes or less. It is the responsibility of the claimant to prove the veracity of the health benefits, not the physician.

The popularity of herbal preparations rests in part on the notion that “natural is safe”. In fact, nature produces some of the most potent toxins and poisons known like botulinum toxin, lysergic acid (a component of LSD), cyanide, snake venom, belladonna and alcohol among others. Marijuana, peyote, mushrooms and moulds all produce substances that alter our body’s normal physiologic processes. All herbal products contain biochemical compounds as all organic living matter does.

Physicians need factual and credible scientific information to address their patients’ questions and concerns. Research continues to present interesting applications for some herbal regimens. For this reason, all herbal preparations should face the same safety assessment playing field, as do all prescription and over-the-counter medications because they are indeed drugs. Where they come from is irrelevant.

If we accept that herbal preparations possess the ability to alter our physiology then we must determine if it has beneficial therapeutic effects. Let us look at some of the latest research for some of the more popular herbal/plant medications; Echinacea, St. John’s wort, garlic, Gingko Biloba and Saw Palmetto. Do they stand up to scrutiny?

Echinacea, derived from the Asteraceae or Compositae family of plants, is purported to fight the common cold, urinary tract infections, vaginal yeast infections and genital herpes among 15 other uses.

Native Americans first used it to treat respiratory infections, snakebites and other ills. It use in the 1800s was a blood purifier and dizziness treatment. In the early 1900s, it was used to treat cold and flu and as an anti-infection agent.

Echinacea preparations may decrease the duration and severity of colds and flu but does not prevent them. Because of the multitude of Echinacea plant sources each with different chemical compositions, it is unclear which preparation is most efficacious. It fails to treat urinary tract infections, genital herpes and vaginal yeast infections.

Saw Palmetto is used to treat the symptoms of an enlarging prostate gland or Benign Prostatic Hypertrophy (BPH). Many clinical studies lasting up to 48 weeks show significant improvement in many symptoms. Patients report a reduced number of daytime and nighttime bathroom visits, easier start to urinary flow, less dribbling after urination and less painful urination.

Its effectiveness seems to be on par with the prescription drug Proscar. However, it does not reduce prostate size or PSA levels. Other BPH medications such as Flomax and Hytrin seem to be superior to Saw Palmetto for relieving symptoms.

The active ingredient of St. John’s wort, hypericin, is possibly as effective for the treatment of mild to moderate depression as the selective serotonin reuptake inhibitors (SSRIs) like Zoloft and Prozac. It is not indicated for severe depression. There is insufficient evidence to support other claims as a treatment Hepatitis C and diabetic nerve pain.

Of the 30 health claims for Gingko Biloba, several studies indicate it seems to be possibly effective for the treatment of dementia from Alzheimer’s or stroke, acute altitude sickness in mountain climbers, vertigo and distance walking leg pain in people with blocked arteries of the lower limbs.

Studies lasting three months to a year show that Gingko leaf extract can stabilize or improve some measures of cognitive and social functioning in patients with different types of dementia. In effect, the research indicates this improvement amounts to a six- month delay in disease progression. There are no head-to-head studies comparing Gingko to conventional medications for the treatment of dementia.

Garlic’s main use is in the prevention of cardiovascular disease. Most of the evidence shows it does reduce total cholesterol levels by four to 12 per cent but is ineffective raising the HDL or good cholesterol levels. Statin medications (lipitor and others) decrease levels by 17 to 32 percent and do raise HDL levels. Garlic can also interfere with blood thinner medications increasing bleeding risk. Patients who need a significant reduction of their cholesterol levels should not use garlic.

Further research will help identify the therapeutically active ingredient(s) of these plants. Consult with your doctor and pharmacist about drug interactions and drug safety concerns before starting any herbal medication especially if you are taking prescription medication.

Links: ConsumerLabs (http://www.consumerlab.com/)
Health Central (http://www.healthcentral.com/centers/OneCenter.cfm?Center=Herbal_Remedies).

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).

Leaves of three, let it be

Dr. Barry Dworkin — Wed, 25 Jun 2003 00:46:16 +0000

Originally published in The Ottawa Citizen June 24, 2003
Original Title: Poison Ivy

During the summer months, it is common to see people come in with peculiar linear or blotchy blistered red rashes. Welcome to poison ivy country.

Poison ivy was named in 1609 by adventurer, explorer and president of the British colony of Jamestown, Capt. John Smith. It belongs to the cashew family.

Found in areas of southern Canada and parts of the United States, it grows as a vine on trees or as a bush in grassy or bare areas. Often you will encounter it along the edges of roads, footpaths or fields, a new shopping mall or a housing subdivision where it does not have to compete with other vegetation. Hiking trails in and around Ottawa-Gatineau post poison ivy warnings.

Poison ivy is readily identifiable. The leaves grow on the stalk in groups of three. Their colouration starts as red in the spring, changing to shiny green in summer, then yellow, red or orange by the fall. Poisonous white, waxy clustered berries appear later in the season.

Poison ivy is related to poison oak (Pacific Northwest and western Canada) and poison sumac (eastern United States). However, these plants are shrubs and have seven to 13 leaves per stem, unlike poison ivy.

The sap (oleoresin) from the vine or shrub, and urushiol oil (from the Japanese, urushi meaning lacquer) are intensely irritating to the skin. One billionth of a gram (a nanogram) will cause a rash. An affected person’s average exposure is 100 nanograms. To put this natural irritant’s strength in perspective, seven grams (a quarter-ounce) would be enough to cause a rash for everyone on Earth.

The oleoresin can remain active on any surface, including dead plants, for up to five years. Collecting firewood over the winter can inadvertently include the poison ivy vine. Burning the vine will release the urushiol into the air leading to lung and eye irritation.

Poison ivy rash is not an infection but a chemical irritation. The fluid within the rash’s blisters does not contain the oleoresin and will not spread the rash. It will spread from person to person if the hands or clothing remains contaminated with oleoresin. Washing the oleoresin from the skin, clothing and surfaces eliminates the risk of contaminating others.

About 50 to 70 per cent of the population is allergic to urushiol, especially those with cashew allergies. The rash appears 24 to 48 hours after contact with the resin. It quickly becomes red and intensely itchy. Blisters can form. Often, the rash appears in streaks where the vine has scratched the skin.

The rash usually resolves one to two weeks after exposure. Some people with no previous exposure to poison ivy will develop the rash seven to 10 days after exposure. Frequent exposure to poison ivy increasingly stimulates the allergic response and the rate of rash and blister formation.

There is a 10-minute window of opportunity after exposure when thorough soap and water washing of the skin can minimize the chance of a rash. Remove any clothing contaminated by the oil, and wash it thoroughly, being careful not to touch the clothes with your bare hands.

Treatment options depend on the severity and discomfort of the rash. The use of antihistamines, cool compresses, Aveeno colloidal oatmeal baths and topical steroid creams can limit mild to moderate reactions.

Do not intentionally break the blisters. They act as a protective covering for the healing skin underneath them. It can lead to secondary bacterial infections, complicating treatment and potentially worsen scarring. Consult your doctor if large blisters form on your hands. It may be necessary to drain the blisters to allow more freedom of movement, reduce hand stiffness and loss of function.

Wet-to-dry dressings on oozing blisters can dry them out so you can apply steroid creams. Your pharmacist can help prepare a Burow’s solution. Apply this solution to a single thin cotton sheet or fabric and apply it to the skin. Allow the fabric to dry over 30 minutes. Repeat the procedure several times. For those who suffer extensive skin damage, your doctor may prescribe a short-term course of oral steroids. The rash usually resolves within two to four weeks. Prevention is a matter of avoiding the plant. Pets — especially dogs — can pick up the resin on their fur, so be mindful after Greenbelt excursions.

Resources:

http://poisonivy.aesir.com/;
http://ncnatural.com/wildflwr/obnxious.html;
http://www.aad.org/pamphlets/PoisonIvy.html

How to avoid mosquito bites – DEET Repellents Must Be Used With Care

Dr. Barry Dworkin — Sun, 23 Jun 2002 00:33:47 +0000

Originally published in The Ottawa Citizen June 22, 2002
Original Title: Don’t Let the Bugs Bite!

Every summer our skin is subject to the mosquito onslaught. Young children’s skin tends to react more strongly from bites. A young child’s immune system has not had the pleasure of the hundreds of times adults have been exposed to mosquito saliva. With age we develop antibodies so that by adulthood our response to these bites is more subdued.

Clinical complications to common North American mosquito bites are infrequent. Complete eyelid closure due to swelling commonly occurs in small children. Similar dramatic swelling of the face can also occur. Eyelid swelling does not often lead to infection. Lymph nodes in the neck can swell in response to scalp and facial bites that can persist for several weeks.

A few simple precautions can help avoid mosquito bites. The skin should be covered with protective clothing such as long pants and long-sleeved shirts. Children’s play areas (such as a sandbox) should be placed in open sunny areas (remember sunscreen use) and not near vegetable gardens, brush or trees. Most bites occur in the early dusk or early dawn.

DEET (N, N-diethyl-meta-toluamide) is one of the most effective commonly used topical insect repellents. In 1946, the U.S. Army developed it for use in insect-infested areas. It was made available to the general public in 1957. Although the exact ingredient or combination of ingredients that repel mosquitoes and ticks is unknown, it is likely to be toluene. Toluene is an organic solvent used in rubber and plastic cements and paint removers. DEET belongs to this family chemical family.

DEET is absorbed through the skin. Since children have a greater body surface area to weight ratio the side-effect risk is greater. Although toxic encephalopathy (brain poisoning) and seizures are associated with its use in children, these rare instances occurred with prolonged exposure to DEET. Swallowing DEET can be fatal. Coma, seizures and hypotension (low blood pressure) occur within an hour of ingestion.

Rashes, hives, blisters, skin and mucous membrane irritation and numb or burning lips tend to be more prevalent with DEET concentrations of 50 to 75% or when used in excessive amounts. There is no evidence that it causes cancer or birth defects.

Commercial preparations are available as sprays and rub-ons. Although comparative studies show only moderate advantage, the effectiveness of each is partly related to the concentration of DEET. A combination of clothing sprayed with an insecticide (NIX) or an odour repellent plus DEET applied to exposed skin surfaces appears to be the most effective bite protection available.

Due to the toxic side effects of skin absorption, DEET concentrations of less than ten percent or none at all should be used directly on children’s skin. Adults should not apply concentrations greater than 30% onto their skin.

DEET sprays should be applied to children’s clothing before they are worn. Entomologists wear a special mesh jacket that is placed in a Zip-lock bag with DEET for two hours. Greater concentrations of DEET can be used in this case. It can be worn over clothing and is effective for many days. Skin absorption is minimized because of the avoidance of direct skin contact. DEET can damage some synthetic fabrics and plastics.

DEET should not be applied to the skin during pregnancy.

Children should not apply DEET themselves. Parents should apply it to their own hands then put it on the child avoiding their face, hands, open sores or cuts. Prolonged or excessive use of DEET, application in enclosed spaces and failure to wash off the repellent once indoors can increase the risk of side effects.

Mosquito coil smoke contains about 70 different volatile organic compounds including allethrin, phenol, benzene, toluene and xylene. Animal studies with long term exposure (8 hours a day, 6 days a week for 60 days) to mosquito coil smoke showed metaplasia (abnormal growth) of skin cells, poor weight gain and lung damage. It should therefore not be used in enclosed or poorly ventilated areas.

Avon Skin So Soft bug repellents contains citronella oil (0.05 to 0.10 %); a safer alternative having less potential toxic effects. It has a very acceptable odor and appears to adhere to the skin better.

Citronella is a volatile oil derived from obtained from the leaves and stem of the plant Cymbopogon winteratus. Used for over 50 years as an insect and animal repellent, it is found in many familiar insect repellent products: candles, lotions, gels, sprays and towelette wipes for use on clothing and people. Citronella is also present in some home lawn and garden pellet products to repel dogs and cats. When used as directed, citronella products are not expected to cause harm to humans, pets or the environment. These repellents are not as effective as DEET and provide about 30 to 40 minutes of protection from bites.

Proper use of these products will minimize any potential for harm and keep the bugs out of your hair.

Product	DEET %	Toluamide (%)
Off Skintastic lotion	7.125	0.375
Off Skintastic for kids spray	4.75	0.25
Muskol with sunblock 15	9.5	0.5
Deep Woods Off	95.0	5.0
Muskol Spray	23.75	1.25
Muskol 8 hour lotion	28.5	1.5