Dr. Barry Dworkin » Pharmacology

Measles outbreak spreads in BC

Dr. Barry Dworkin — Fri, 09 Apr 2010 11:28:14 +0000

Madely Health Headlines Commentary for April 9, 2010

Source:

B.C. measles outbreak expands to 26 cases

H1N1 pandemic severity update and the effectiveness of antivirals in otherwise healthy adults

Dr. Barry Dworkin — Wed, 09 Dec 2009 15:03:47 +0000

Madely Health Headlines Commentary for December 9, 2009

Sources:

British researchers say little evidence Tamiflu works, but WHO says the drug is useful

Swine Flu Pandemic May Be Less Severe Than Expected

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.

Protecting immune system from attack

Dr. Barry Dworkin — Fri, 12 Nov 2004 22:14:36 +0000

Originally published in The Ottawa Citizen Friday, November 12, 2004
Original Title: Infection control for dummies

Infection control can be a complicated matter, especially for viruses that spread as easily as the flu. The flu can spread through direct hand-to-hand contact, via airborne droplets (fomites) after a sneeze, and with contact with recently touched surfaces such as doorknobs, telephones, countertops and desks.

Preventing infection does depend upon “boosting your immune system,” but not in the way some believe it to be.

Our immune system begins at birth as a bunch of raw army recruits. They are healthy and strong but lack experience at recognizing and fighting the enemy. With training and combat they gain experience and become more efficient in their role as a standing army. Some are selected for special-forces duty and reconnaissance missions. They are able to track down and identify their target so that the army can move in and destroy it.

Our immune system follows this analogy. It has the potential to respond to threats from viruses and bacteria. Indeed, it will respond well to minor threats such as colds and minor cuts and scratches. But other pathogens, like the measles virus, polio, diphtheria, meningitis, typhoid and hepatitis, among others, can overwhelm the immune system. It tries to fight back, sometimes succeeding but with great collateral damage to organs and other structures.

If the system is trained to recognize these pathogens before the war, it stands a greater chance of protecting the body. This is the underlying reason why vaccines work.

Vaccines stimulate the immune system to develop antibodies, the body’s special forces that will seek out, identify and target the invader for the main battle group. Without these specific antibodies, the immune system is not co-ordinated to quickly prevent the attack and damage; you either lose the battle, suffer collateral damage or play a game of attrition — a draining experience.

Some argue that exposure to the pathogen is the preferred route of developing immunity, as opposed to using a vaccine. Indeed, the infected person will create antibodies and immunity if they survive the real infection. But this may come at a cost of permanent damage.

The vaccines contain either killed or weakened strains of the organism that have orders of magnitude less potential to cause harm compared to the original virus or bacterium.

Indeed, some will disagree with me and cite Internet references or studies that indicate the opposite. The response is that the studies to support vaccine use far outnumber the ones that imply the opposite. There is no conspiracy.

The flu vaccine is a “best assumptions” vaccine. It is predicated on what flu virus strains we expect will come into Canada and the United States from other regions of the world. If the assumption proves incorrect or incomplete, the importance of proper hygiene practices becomes more apparent.

What other infection control measures can people take for the upcoming flu season?

If you have the flu, isolate yourself from others and do not go to school or work. Wearing a properly fitted surgical mask and goggles with side protectors will help prevent catching the virus from an infected person or transmitting it to a caregiver.

Ineffective hand washing after sneezing into a tissue or coughing into the hand will leave viral/bacterial organisms on the hands. The perfect cleanser does not exist. However, a combination of products will offer substantial protection.

Soaps are excellent detergents and remove grit, grime, dirt, soil, and other organic compounds. The non-antimicrobial soaps fail to remove resident disease-causing bacteria from the skin but do remove some transient bacteria. Sharing a plain soap bar has the potential to spread disease because it can become contaminated.

Numerous studies indicate that alcohol (ethanol) washes dramatically reduce hand bacteria and viral counts after washing for 30 seconds. The alcohol gels should be used for at least 20 to 30 seconds and cover the entire hand and under the nails. Apply about a nickel- to quarter-size blob in the palm. If the hands dry in less than 15 seconds, insufficient gel was used.

There is an antiviral flu medication available called Tamiflu. It must be used close to the onset of the flu and will only reduce, not eradicate the symptoms and duration of the illness.

Carry a small squeeze bottle of alcohol gel with you and use it routinely to prevent the usual winter colds and flu this season.

Prepare now for the flu season

Dr. Barry Dworkin — Mon, 18 Oct 2004 22:18:43 +0000

Originally published in The Ottawa Citizen October 18, 2004
Original Title: The HN factor

New information and reports of bird flu have shifted attention to the possibility of a new flu pandemic. The most lethal pandemic in our history occurred from 1917 to 1919 killing an estimated 20 million to 50 million people.

The World Health Organization (WHO) released a statement this month encouraging governments and pharmaceutical companies to begin production of bird flu vaccines.

To date there has not been any documented human-to-human transmission of the bird flu virus, but it is the high mortality rate for those who have caught it that has garnered attention. Millions of chickens have been killed during the past few years to contain the latest incarnation of the bird flu.

Why does the flu pose such potential danger, what are its origins and why does the vaccine change every year?

Imagine a beach ball with a small stick trapped inside it. Covering much of the beach ball’s surface is gritty sand. This is what influenza looks like under an electron microscope. The stick is the genetic material that infects us. The beach ball is the shell that protects the genetic material until it can invade our cells. The grains of sand represent the pieces of protein called antigens protruding out on the shell surface.

The antigens are designated with the “H” (hemagglutinin) and “N” (neuraminidase) monikers. For example, the bird flu has a designation of H5N1.

If our immune system is sufficiently primed for this viral invasion it will attack the antigens on the shell. The shell will break open and the immune system’s cells move in to destroy the genetic material before it causes disease. Our bodies develop immunity with each exposure to the flu virus and with each vaccination.

Many viruses slowly mutate or change over time. Most healthy people can adapt to these minor changes.

Epidemics and pandemics occur when the virus (usually Influenza A) undergoes a radical genetic change over a short time. This occurs when a human and bird virus both infect an animal simultaneously. The viruses swap genetic material, forming a new strain.

Because the immune system has never seen this new strain, it has no counter-measures to fight it; the body is defenceless.

Scientist Yoshihiro Kawaoka, of the University of Wisconsin-Madison and the University of Tokyo, looked into why the Spanish flu was so lethal. He stated, “We found that just one gene called HA, hemagglutinin, is sufficient to make a benign virus pathogenic.” The results of the study were reported in the journal Nature.

“One of the hallmarks of the 1918 Spanish flu is hemorrhage in the lungs,” said Mr. Kawaoka.

The suspicion is that the Spanish flu originated from birds. The research team wanted to look for clues within the genetic code of the virus that could help predict future lethal strains before they had a chance to spread.

Those most vulnerable are people over age 65, pregnant women, young children and those with chronic illnesses like asthma diabetes. Hospitalization rates for children under the age of two who have the flu are equal to those over 65.

The historical record of flu pandemics, the last in 1968, indicates a cycle of roughly 20 to 30 years; we are overdue. The WHO’s concern is that the world is unprotected against the bird flu virus, hence its recommendation for vaccine development.

The vaccine’s ability to protect you is determined by how closely they can match the strains that will arrive in North America each year. With a close match, protection rates against clinical influenza approach 70 to 90 per cent.

The flu vaccine contains dead viruses; it does not cause the flu. The vaccines cause side effects less than five per cent of the time. These commonly include a low-grade fever and fatigue for eight to 24 hours after immunization; minimal discomfort compared to the actual flu.

The vaccine is recommended for:

Persons 65 years of age or older;
Residents of nursing homes and chronic care facilities that house people with chronic medical conditions;
Adults and children who have chronic heart and lung disorders, including children with asthma;
Adults and children who with chronic diseases including diabetes mellitus, kidney failure, anemia or poor immune system function;
Healthy pregnant women in their second or third trimester;
And you!

Ottawa Public Health does not recommend the vaccine for people with:

A previous allergic reaction to influenza vaccine;
An allergy to eggs or thimerisol;
A changing neurological condition;
A history of Guillain-Barre Syndrome;
A history of Oculo-Respiratory Syndrome.

Studies in the United States demonstrate marked cost savings to the health care system and increased work productivity. In one study, vaccinating working adults reduced absenteeism by 50 per cent.