A Tenuous "Alli"ance

It appears that GlaxoSmithKline has recieved approval to market Alli overseas to our European cousins.

This means the product will now be proposed for final approval by the European Commission and marketing authorisation could be granted in the coming months. On licence grant, orlistat 60 mg would be the first licensed weight loss aid available without prescription throughout Europe.

You hear that? An FDA-approved weight-loss supplement! It's a miracle!

Alli was actually released to US markets last summer as one of the more unusual Rx-to-OTC product conversions that we've seen recently. Popular once prescription-only Zyrtec I expected, but Alli was really out of left field. I actually meant to blog about Alli when it was released, but somehow it got away from me. Now I can do so to commemorate its release across the pond.

What is Alli? Alli contains the same active ingredient as a prescription drug that was developed by the Swiss company Roche Pharmaceuticals--the generic name for it is orlistat. It is the first over-the-counter drug approved as a weight loss aid by the FDA, mostly because there's good clinical data that it's actually effective when used properly.

OTC "diet pills" generally contain high doses of stimulants/caffeine, claim to suppress appetite, or somehow purport to "melt fat" or "block calories." Some stimulant weight-loss supplements contain as much caffeine per capsule as three cups of coffee and have "serving sizes" of two or three caps at a time! Clever wording is usually employed to conceal the simplistic nature of these products--Zantrex-3 refers to its caffeine content as "a proprietary xanthine-based stimulant." Caffeine is part of a chemical family called methylxanthines. Other times numerous herbal ingredients or Latin names for botanicals obscure the true content of the supplements except to the most attentive consumers.

Alli, true to its claims, is different. How does it work?

First, a bit of basic biochemistry. There are three major "macronutrients" required for human nutrition--carbohydrates (sugars), lipids (fats), and proteins. All of these are absorbed through the intestine whenever you eat. Macronutrients are then delivered to the liver or various cells of the body that can use them. Carbohydrates are easy; the body breaks them down into smaller units and uses them to produce ATP, a small molecule that is the primary source of energy for the body at the cellular level.

Proteins and fats cannot be used directly by most cells. Instead, the liver processes them into more readily useful forms. Some proteins can be converted into glucose, the most basic (and preferred) form of fuel for body systems, especially neurons. Fat metabolism is more complicated and involves many steps that ultimately culminate in the release of free fatty acids; these are also usable as fuel by many body systems.

If you eat too much of anything, be it proteins, carbohydrates, or fats, the body is remarkably efficient at storing the excess energy produced. The most energy-dense form of stored energy is fat; fats produce the most energy (in calories) per gram. This fat winds up getting stored throughout the body as a reserve for times when food sources are scarce. Each pound of fat on your body represents a total stored reserve of 3,500 calories. Yum!

I've heard it mistakenly stated that you "can't get fat" eating a high-protein diet because "carbs make you fat" or, more obviously, "fat makes you fat," but this is completely false. Your body can (and will) make fat out of anything the liver can get its...um...lobes on.

What does this have to do with Alli?

Alli is not actually absorbed into the bloodstream. Instead, it floats around in the intestines and binds to fat molecules, preventing those from being absorbed. If your body doesn't absorb the fat molecules, it can't process them--in a sense, it's like you never ate them in the first place. Alli binds an average of 25% of consumed dietary fats, potentially reducing caloric intake from a fatty meal significantly.

Problem: Alli is not magic. It cannot break the laws of physics and destroy matter (and I suspect converting fats to energy in your intestine would have odd effects, were it possible). If you don't absorb the fats, they still have to go somewhere. Since they're already 3/4 of the way through your digestive tract, and getting the whole system to flow in reverse is both very unpleasant and very difficult, I'll let you think about it on your own for a second.

A funny aside: The makers of Alli recommend that you not wear light-colored pants while taking it.

I personally like to think of Alli as "negative reinforcement." Operant conditioning is basic psychology. Continuously eat fatty meals on Alli and you're going to suffer chronically oily stools. You're either going to learn to control your dietary fat intake or you're going to throw away your Alli.

This isn't to say that Alli is bad. As part of a comprehensive diet and exercise plan, it will help you lose more weight, even if it's only a few extra pounds. But the reason Alli can get FDA approval, aside from the fact that it's been subjected to more rigorous clinical trials, is that Alli doesn't claim to be magic. "Eat all you want and still lose weight!" "Melt fat away while you sleep!" Due to loose regulations, dietary supplement manufacturers make these kinds of claims all the time. But the makers of Alli had to be realistic about the potential benefits of their drug to get it approved. This isn't a bad thing. It's what we should expect from all drug and supplement manufacturers--indeed, it's what should be legally required.

Anyway. Now Europeans can experience the thrill of Alli without a doctor's prescription!

...just remember to wear dark pants.

But Think of the CHILDREN!

You ought to recognize that line as a classic refrain of those in a state of "moral panic."

According to a recently released study, 3% of all children and adolescents in the United States go without health insurance at some point in a given year:

That translates into almost 3 million U.S. children with no medical care at all and no access to prescription drugs over a full year. Slightly more than half of that number qualify for public coverage but aren't enrolled.

Overall, more than 9 million U.S. children are uninsured; some 18 million have a coverage gap at one time or another, according to the study.

But, surprisingly, this includes kids whose parents have coverage:

The authors of the first study looked at data from 2002 to 2005 on children and adolescents under the age of 19 living with at least one parent. The study included more than 39,000 participants.

Their analysis found that 3.3 percent of children and adolescents were uninsured, even though they had at least one insured parent. (emphasis mine)

What about demographic information?

Uninsured children and adolescents were 58 percent more likely to be Hispanic than white non-Hispanic; had double the odds of being from a low-income versus a high-income family; were 48 percent more likely to be from a middle-income rather than high-income family; and twice as likely to come from a single-parent home than a home with two married parents.

...children whose parents had less than a high school education were 44 percent more likely to be uninsured; they were also 64 percent less likely to be insured if their parents had public coverage rather than being privately insured.

None of this should be a surprise. Poor kids don't have adequate health care coverage. Middle-class kids are less likely to be insured than kids from richer families; kids whose parents make between $38k and $72k a year are just as likely to be uninsured as their poorer counterparts. Kids with parents who have limited education are less likely to be insured, probably because the parents are less likely to have jobs that offer comprehensive family healthcare plans.

Why haven't we passed legislature to provide all children with health care coverage? Remember, the people who typically vote against candidates daring to propose universal health care are also the people who are most opposed to family planning.

"But N.B.," say some members of the audience, "the article says that over half the kids involved qualify for public assistance but aren't signed up. That's the fault of parents, not the government."

You're right. But not providing health care for children is sheer negligence, and we punish people for child neglect already. The definition of child neglect is "any recent act or failure to act on the part of a parent or caretaker which results in death, serious physical or emotional harm, sexual abuse or exploitation." It is considered neglect to fail to provide for a child's basic needs, and medical care is included among them.

About half of U.S. children without health insurance had to go without medical care or prescription medications while they were uninsured, said researchers from the University of Rochester Medical Center. Even more children went without preventive care, including receiving necessary vaccinations.

If you don't see why this is a problem, you're part of it. And if you don't see why there need to be laws mandating health coverage for children (and adequate government assistance for those who need it), you're still part of the problem. Until there are laws mandating health care coverage for all children, we're losing a battle. There are kids out there who don't get treatment for the most basic illnesses because they lack health care coverage. Maybe one of them is yours.

"Children are like flowers," they say. "You can never have too many."

If you aren't watering your garden and your flowers are dying, maybe you should rethink that assertion.

So...please! Think of the children!

One More Thing to Write your Congressman About

PalMD has pointed out yet another area of healthcare that is clearly lacking and potentially in need of intervention.

In order to know how much short-acting insulin to take, a diabetic has to insert a test strip into their glucometer, prick their finger with a small needle, and touch the drop of blood to the test strip. This is usually done (at least) on waking, before every meal, and at bedtime---at least four times per day. Thankfully, blood glucose monitors are quite inexpensive and last a long time. Test strips, however, are expensive and disposable. How expensive? Depending on the brand of meter being used, and how many times you need to test, $30-$200 per month. These strips are usually not covered by insurance.

To give a comparison, good medical treatment for coronary heart disease, which usually requires about four medications, costs around $16/month. Older forms of insulin are also rather inexpensive (but the newer ones are costly). Without insulin, diabetics die---fast. Without test strips, diabetics don't know how much insulin to use.

He's absolutely right--and this is an absurd situation. Why don't insurance companies generally pay for something that is at least as necessary as insulin itself?

So...do something about it! Write, using this link. Or perhaps this one. Do both. The first is for the House and the second the Senate.

Don't know what to say? Try starting with what Pal suggested:

Diabetes is a serious disease affecting more than 20 million Americans. Part of the treatment of diabetes is the regular testing of blood glucose levels. In order to do this, diabetics must purchase glucometer test strips, which cost around a dollar a piece, and are usually not covered by insurance. For diabetics, especially those who have financial difficulties, the cost of test strips, which can be up to hundreds of dollars per month, makes diabetic treatment impossible.

I respectfully request that you look into potential solutions for this very serious problem, and bring this to the attention of your colleagues.

Sincerely...

Retail Pharmacy: Bringing Home the Bacon

I'm afraid that I must both simultaneously agree and disagree with a recent post by The Angry Pharmacist about an issue that hits fairly close to home.

Pharmacy professors wield the term "patient care" to their students like its what brings home the bacon every pay-period. Hate to break it to you kiddies, but they are full of shit.

You know what makes the store money? Filling prescriptions. Like it or leave it, filling an Rx fills your paycheck. This precious 'patient care' where you go out front and waste your time consult Mrs Smith on how to take her atenolol for the 4th time this month ends up costing the store money in the long run because you are not filling prescriptions. Spending hours with patients may make you feel warm and fuzzy, but getting off your ass and filling Rx's is what keeps your paychecks from bouncing.

As one of those ignorant pharmacy students, I'm sure my opinion is worthless, but I think that this sort of thinking is both immensely practical and startlingly backwards.

When I settled on pharmacy as a career I was 16. No one in my family was a pharmacist. No one in my family was a healthcare professional of any sort, for that matter. What initially appealed to me was medicinal chemistry. I wanted to research the next generation of drugs, develop treatments or cures for man's most devastating illnesses, and spend most of my life in a lab surrounded by bubbling beakers.

Once I actually got into heavy lab science (analytical chemistry) I decided I hated it. I made some phone calls and arranged for a summer job at a pharmacy in my hometown. After about three weeks of working there I was solid enough on all the mundanities of the job (register duty, cleaning and organization, data entry, etc.) that I was able to start dedicating my "brain time" at work to learning about drugs.

I started learning drugs in the most disorganized fashion possible, which is probably good because my mind wraps itself around trivia and traps it forever. I asked questions of the pharmacists on duty. I pulled package inserts off bottles while I worked and read eagerly. I was lucky to have preceptors that were willing to take the time to answer my inquiries and who encouraged me to continue trying to soak up as much knowledge as I could. The "big secret" that helped everything fall into place was the pharmacist who told me that drugs in the same class have similar names (like all ACE inhibitors ending in "-pril"). Suddenly I realized that I could generalize my knowledge about some specific drugs.

What was the point of that long story?

I started out thinking I wanted absolutely nothing to do with patients because I hated dealing with people and loved chemistry. Loving chemistry translated into loving drugs. I started studying drugs in a vacuum, practically absent of other knowledge about the human body. I learned about the functions of the body based on the activity of drugs, not the other way around. This is probably the most detached-from-reality way to go about the process. The people involved were irrelevant. The drugs were cool. They weren't.

Four years later I live for patient care. Not because I necessarily like patients more, although I did discover that I'm not as misanthropic as I thought. No, I live for patient care because patient care is when I'm getting the most out of the effort I've put into learning things. Not being able to do patient care would be like telling a carpenter that he needed six years of school to get licensed but that on the job all he'd be allowed to do is hold the toolbox and make sure that the boss was using the right tools.

But N.B., you're thinking, TAP didn't say patient care was unimportant or bad. He said it wasn't profitable. "Patient care" doesn't pay the bills. Dispensing prescriptions does.

I agree that somebody does need to be paying attention to whether or not a business is making money. I don't ever want to be that person. That's why I would never start my own pharmacy, although I considered it at one point (it's also business suicide in today's climate, but whatever). I want to take care of patients without being worried about whether or not I'm filling enough scripts per week to pay my overhead, and if that makes me an empty-headed pharmacy student, so be it. Because if script volume is the most important indicator of whether or not I'm doing a good job then I am not a clinician, I'm a salesman.

Modern big-box stores and corner pharmacies are taking a loss on operating their pharmacy departments. It's the honest truth. The money is made elsewhere. How else could the big-boxes justify giving away generics at $4 or select antibiotics for free? They know the pharmacy doesn't make money; the pharmacy attracts customers. The pharmacy is not making money no matter what. What you are doing by filling more scripts is not making money, it is losing less money.

TAP's opinion on this subject is that the solution is to target the PBMs, or pharmacy benefits managers, that screw pharmacists over by reimbursing them considerably less than what they deserve. A business cannot operate by selling its product at a loss, but the PBMs essentially say something like this: "Well, you collected the patient's $10 copay and you charge uninsured patients $150 for the drug? It costs you $120 to order the drug? Yeah, we'll give you $90 + $3.50 for the dispensing fee, take it or leave it." Fix the industry regulations that let the PBMs get away with robbery and we're all good.

Because I'm young and naïve, I'm too stupid to know my ideas are bad. So here's mine. Pitch out the idea that pharmacy is a business altogether. Fuck pharmacy entrepreneurship. Stop assuming that pharmacies should operate as "drug sellers" and start thinking of them as "drug providers." The old business model doesn't work anymore. No longer does Joe the Pharmacist open his own shoppe on the corner and grind powders with a mortar and pestle all day so that he can punch capsules or roll pills. Nobody sells patent medicines anymore (unless you count the altmed scammers). Pharmacy is now ruled by giants, not Joes.

We should turn pharmacy over to the ultimate giant--the Feds. No more corpo-pharma. Pharmacists become government-salaried employees. Prescription drugs (not OTCs), patient care, whatever, they all become services funded by your tax dollars, free or practically free depending on your income level. Pharmacists already counsel for free. They're already giving away their services without collecting a dime--because it's viewed as a professional responsibility. The only thing stopping them from giving away the drugs is the perception that it's necessary to make a profit because no one will keep you afloat otherwise. Currently, that's true. But it doesn't have to be.

Laugh if you want, call me a socialist (the ultimate bad word), whatever, but at least have the courtesy to tell me why you think it wouldn't work. Spain has a system sort of like this. Germany has its own version. A lot of European countries have variations on this model; even if the pharmacies aren't government-owned, public healthcare provisions cover the cost of patient care. Clearly the government is not expecting pharmacies to "operate at a loss." If it did, the pharmacies would go out of business and there would be be no more pharmacies, which is a rather self-defeating model if the purpose of having universal health coverage is to make sure people have access to care.

I know I'm committing the error of "is versus ought" here, saying all this. But that's okay. The current fight in pharmacy is trying to keep pharmacy a working "business" under the present model. We'll never win. Pharmacy is too big now for Joe pharmacist to contain its girth. The business end of pharmacy needs to be abandoned altogther in favor of a patient-focused model.

Here's the bottom line. If you operate a pharmacy (or a doctor's office, for that matter) like a business, profit must trump patients. This is contradictory to every code of medical ethics in existence. It's true, you might take some patients at a loss in "real" practice. But there still exists a conflict of interests; as long as pharmacists are concerned about keeping a roof over their heads and worried about "the bottom line" they will never be giving 100% to the patients they serve. Healthcare is a service field. It is lucrative for many people. But ideally the point of being a doctor or pharmacist is not to get rich. It is to help people--and be sufficiently compensated so that one can live comfortably during his "off hours."

Don't recoil reflexively when someone says "socialist" or "government-subsidized." Abandon the idea that individualism--i.e., capitalism--is the best solution. You can't even start your own pharmacy anymore and have it survive; claiming that starting a pharmacy is a sound business idea at this point is utterly foolish. Quit thinking about you and how you want to run your own business which is the American dream. Stop being a selfish prick and put your patients first!

And if that's not why you went into healthcare, leave. Because we don't want you here.

Student Finds Classical Reporting on "Holistic" Medicine Still Lacking Critical Rigor

The rise of "alternative medicine," if you can claim that it has risen at all, has mostly been due to word of mouth and unwarranted exposure by an uncritical press. Seeing as how CAM itself never actually changes, it should be no surprise to anyone that neither does reporting on it. We hear the same fallacies, the same appeals to authority and tradition, and the same overweighting of anecdotal evidence over and over again.

So I wasn't even a little shocked at this typical article on the common cold.

ABCNews.com asked four holistically minded doctors what they do when they feel under the weather. Their prevention and treatment advice might help you dodge or short-circuit the next bug that comes your way.

I'm not even entirely sure where to begin. "Holistically-minded doctors?" What does that even mean? Proponents are going to spout some gibberish about doctors that "treat the whole person, not just their symptoms," but let's see what these doctors recommend to "treat the whole person."

Let's start with Dr. David Rakel, MD.

There's no firm evidence that any medication or herb will prevent the common cold, said Rakel.

Hey, cool, he's actually concerned with whether or not there's evidence for the stuff he suggests!

At the first sign of symptoms, the goal is to attack the virus early because it replicates the most within the first 48 hours, pointed out Rakel. He might drink more green tea, which appears to have antiviral and antibacterial properties. And he would also drink three big glasses of orange juice to get more vitamin C...

...besides consuming more liquids, Rakel might take 20 to 30 milligrams of zinc acetate lozenges twice a day to improve his immunity. He takes zinc only for the first two or three days of a cold, when he feels it's most effective. He might add andrographis, an herb that's sometimes called "Indian echinacea." He would take 400 milligrams of this immune-stimulating herb three times a day.

That's why when it comes to his own health he takes a shotgun approach and tries everything that has ever been suggested for treating the common cold. Vitamin C, zinc, green tea (antioxidants), and "Indian echinacea," which must be better than "Western echinacea."

At least Dr. Rakel gets an annual flu shot, but he bemoans the presence of thimerosal in flu shots. I guess the fact that thimerosal-free flu shots is not important to him, or maybe he just thinks the CDC has it all wrong.

Strike one, MD's out. Who's next? Lynne Shinto, ND. You can probably guess where this is going.

She says she thinks that too much sugar can weaken immunity...when she gets a cold, her philosophy is to let it run its course. She'll turn to the usual suspects: bed rest, more fluids and chicken soup -- or because she's Japanese-American -- miso soup with shiitake mushrooms, fungi known for their immune-strengthening compounds.

Go Lynne! You strengthen that immune system! Is that the humoral or cellularly-mediated immune system? What do you mean you don't know? You're just sure it works? Well, as long as you're treating the real cause of disease instead of just addressing symptoms, like a good holistic doctor.

These approaches may make the symptoms feel better, she admits, but they likely won't make a cold go away faster.

Oops. I guess not. So you fail at both science and pseudoscience.

If Shinto's sinuses are congested, she turns to an "old naturopathic therapy" thought to stimulate the immune system. Called hydrotherapy, she might stick her bare feet in hot water for three minutes then in ice-cold water for 30 seconds, and she repeats this hot-cold sequence three times.

This is a fantastically plausible treatment for nasal congestion. Maybe the alternating peripheral vasoconstriction and vasodilation...no, this really is so implausible as to not warrant investigation.

What about another MD's perspective? Surely a second opinion is worthwhile. Dr. Kevin Barrows?

He's a big believer in meditation and has found this mind-body approach helps increase his awareness of subtle body shifts, a tip-off that he may be getting sick. For him, a sore throat is his early warning sign of a cold, his cue to start taking echinacea.

That's great, doc. I'm glad that you can recognize one of the most common symptoms of the common cold as...indicative of the common cold. But he didn't learn that in medical school. No, he figured it out through meditation! Once he determines that his chakras--er, his throat hurts--he knows it's time to start taking echinacea, the herb that a Cochrane review states "shows inconsistent benefit."

Sixteen trials including a total of 22 comparisons of Echinacea preparations and a control group (19 placebo, 2 no treatment, 1 another herbal preparation) met the inclusion criteria. All trials except one were double-blinded. The majority had reasonable to good methodological quality. Three comparisons investigated prevention; 19 comparisons investigated treatment of colds. A variety of different Echinacea preparations were used...

...there is some evidence that preparations based on the aerial parts of E. purpurea might be effective for the early treatment of colds in adults but the results are not fully consistent.

I know that whenever I have a problem, I'm willing to rush out and spend money on things that "might work."

Outside of a mental health context, I know that if I ever had a doctor who suggested "meditation" as a serious method for identifying or treating any illness I'd pull up my pants and walk out the door. Three doctors I'd never want to visit--assuming that their beliefs are being accurately portrayed in this article. Well, what about Dr. David Leopold, our fourth contestant?

At the first sign of a cold, Leopold treats his symptoms extremely aggressively. His goal is to support his immune system so that it helps clear the virus and slows down the spread of symptoms.

He takes zinc gluconate lozenges, drinks plenty of herbal tea and also uses a liquid tincture of echinacea. Despite research that questioned the herbs' benefits, "I'm convinced that most of the well-done studies of echinacea suggest it seems to be effective for reducing the severity and duration of a cold."

Just what I need, a doctor who flunked both statistics and immunology. No thanks.

The thing is, I'm not entirely sure that the blame is entirely on the doctors being quoted here. Now, granted, I don't think that their words (or positions) are being fabricated; I'm sure that, when interviewed about their "holistic medicine" use, all of these doctors (and the naturopath) volunteered honest information.

But here's the problem. This "sound-bite medicine" doesn't actually leave room for--or invite--serious discussion of anything beyond "some doctor said you should try this." And, in the interest of "unbiased journalism," the reporter behind this story didn't bother to fact-check any of the claims made by the doctors. After all, they're just harmless claims; the article isn't about "what is good medicine" but rather opts to provide some opinions by licensed medical practitioners.

Unfortunately, this approach is seriously misguided. Most people think of physicians of all stripes as having a good, solid understanding of medicine, and this implicit trust that doctors know what they're talking about is crucial. If patients think doctors are idiots, why would they ever solicit one for an opinion? The drawback to this is that off-the-cuff "opinions" about vitamin C, echinacea, or other various treatments that don't stand up as effective under serious scrutiny reinforce the misconception that these treatments actually work. Just try telling a patient whose doctor takes vitamin C that vitamin C doesn't treat or prevent colds. "If it doesn't work, why does my doctor do it?" What surprised me about this article is that it didn't even contain the "token skeptic" interview, but then, the article is subtitled "what alternative medicine experts do when they get sick."

Physicians who succumb to non-evidence-based thinking do more than harm themselves. They drag down patients with them, even patients they'll never meet, because their endorsement of unproven remedies assures that these treatments will never die out despite the immense evidence against their efficacy. As long as there are doctors promoting these remedies, no amount of double-blinded, well-controlled, properly randomized research is going to convince the public that they aren't effective--because their doctors, expected to be the gatekeepers of knowledge, are ignoring it.

But Doctor, I NEED Antibiotics!

How often do you go to the doctor? What prompts you to seek care?

For many people, the answer to that question is "at least once a year" and the reason is upper respiratory tract infection (URTI). Because of the amount of time and effort involved in isolating precisely what is causing an upper respiratory tract infection, doctors quite frequently prescribe unneeded antibiotics:

Various bacterial respiratory infections were diagnosed during 6.5% of physician office visits in 1999. One or more antibiotics were prescribed during 51.0% of those visits. The probabilities of resistance to the most frequently prescribed antibiotics varied from 20% to 40% and showed a weak positive correlation with the frequencies of antibiotic prescriptions.

It is a well-established fact that a huge percentage of antibiotic prescriptions are dispensed for conditions where they will have no effect, such as the common cold, simply because doctors feel that they have some obligation to write patients a prescription--or because the patients pressure the doctor and insist that they need an antibiotic.

But statistics released in this month's Pharmacist's Letter make the issue very clear. Overtreating with antibiotics does more harm than good.

There's only a 1 in 4000 chance that an antibiotic will help most acute upper respiratory infections.

But there's a 1 in 4 chance of diarrhea...a 1 in 50 chance of a skin reaction...and a 1 in 1000 chance it'll cause an ER visit.

...antibiotics [overuse] can also lead to more resistant infections that are harder to treat.

Now, as always, I encourage readers who believe that they might be suffering from any illness to consult their physicians. But think about those numbers for a second. There's only a 0.025% chance that it's going to do you any good to beg your doctor for an antibiotic prescription. The odds that you will wind up in the ER because of a bad antibiotic reaction are higher than the odds that the antibiotic is going to do you any good.

This does not mean that you should avoid antibiotics at all costs, believing that the risks always outweigh the benefits, because that is patently untrue. Keep in mind that these numbers only pertain to (generally non life-threatening) respiratory infections. What this really mean is that you should ask your doctor to be straight with you, especially if you are going to the doctor because you're coughing up phlegm or have a stuffy head. "Do you really think I need an antibiotic?" Make it very clear that you will take no for an answer if it is that physician's professional opinion that you don't need one. They didn't go to school for nothing.

Like Decaf Coffee, but More Dishonesty

I got a kick out of this article about a "new" dietary supplement that supposedly contains the FDA-banned stimulant ephedra while still being legal through various loopholes:

Garza, a bodybuilder who nearly won the Mr. USA competition in 2004, said XP2G is manufactured for his store by a private lab.

He said his pills are made from the same plants used to make traditional ephedra products but lack the ephedrine alkaloid chemicals named in the bans.

Garza said because XP2G lacks those particular chemicals, it does not present the same risk of side effects as traditional ephedra products, and it is not in violation of the bans.

Hmm. So it contains "ephedra" but it doesn't contain ephedra. Do you follow?

Ephedra is actually the name for a genus of plants. Extracts from the Ephedra sinica plant, known in Chinese medicine as ma huang, contain the stimulants ephedrine and pseudoephedrine (yes, the same stuff that's in Sudafed). The popularity of ephedra stems from its so-called "thermogenic" properties--it increases heart rate and blood pressure and raises blood sugar by stimulating the sympathetic nervous system. Most people know the sympathetic nervous system as the system responsible for the "fight-or-flight" response. Essentially, ephedrine acts on the same cellular receptors that epinephrine does. Epinephrine, if you aren't aware, is the same thing as adrenaline; they're just different names for the same chemical.

So what Garza is claiming that his proprietary formula contains parts from ephedra--the plant--but not the alkaloid stimulants that make ephedra "worth" adding to diet pills in the first place.

Why would you do this? Well, because, as I've previously stated, most people don't read anything beyond the front of the bottle when they're buying drugs or supplements. By being able to put "new and improved! Totally contains ephedra!" on the packaging, Garza will sell more product, especially to consumers who liked the old ephedra products that are now subject to FDA ban. What those consumers probably won't realize is that they're being scammed even worse than they were before; the manufacturer is using some loophole to claim the formulation contains ephedra when it doesn't contain the chemicals that make ephedra desirable. It's a bit like selling "coffee" to caffine junkies on the basis that your product "contains real coffee extracts!" without letting on that your product is actually decaf.

More troubling is the fact that Garza may, as they say in France, be totally full of merde:

University of Maryland professor Dr. Fermin Barrueto said legal ephedra is only a marketing gimmick. He said the only way to remove banned chemicals from ephedra is through a complicated extraction process that manufacturers are unlikely to perform.

Which means one of two things: The manufacturer is lying about including ephedra (and not including it, but listing it on the label anyway), or the manufacturer is lying about lying about including ephedra (including it despite it containing the banned alkaloids).

As they said in Smash TV: Big money! Big prizes! I love it!

It's Ozone Action Day: Don't Use Your Inhaler

Do you remember the CFC reduction efforts that went into effect in the latter half of the 20th century? CFCs, or chlorofluorocarbons, are a class of compounds that were traditionally used as refrigerants, solvents, or propellants in aerosol spray cans. When scientists determined that CFCs were contributing to the hole in the ozone layer. CFCs participate in a reaction with ozone where they act as a catalyst--i.e., they are not used up--that breaks ozone down into oxygen gas. Because individual CFC molecules are not used up in the reaction, a single CFC molecule may continue to break down thousands of ozone molecules over its lifetime.

What does this have to do with inhalers? By the end of 2008, CFC-containing inhalers will no longer be sold.

Traditional inhalers used to treat respiratory diseases like asthma used CFC-based propellants to deliver an aerosolized spray of medication directly to the lungs. But the time has come to phase out the old inhalers and replace them with new, more environmentally-friendly alternatives. The replacements, HFA inhalers, are just as effective as the old standbys without causing damage to the ozone layer or contributing to greenhouse gas production. The switch is a good thing, on the whole.

For once, Pharma is releasing a bunch of variations on their old products that aren't just a scam to extend their patents. They're actually doing something to help the environment. Y'know, aside from the fact that they're doing so because of Federal mandate.

There are a few minor issues that must be addressed. The new inhalers are just as good as the old ones, but FDA regulations consider them to be different, non-equivalent drug formulations. This means that you can't simply switch back and forth from CFC to HFA--in most states, the physician who writes the prescription must specify that the inhaler to be dispensed is an HFA inhaler. HFA inhalers are also going to cost slightly more--about $50 versus $30 for the old inhalers. But many manufacturers are distributing coupons that might help reduce costs for patients making the switch.

So if you use an inhaler, be prepared--you're going to have to switch, and soon. But the sooner the better, really. With every puff you're taking on an HFA inhaler instead of a CFC inhaler, you're contributing to the efforts to repair the ozone layer. That's like saving the world, one inhalation at at time.

New and Improved! Now With Even MORE Sodium!

Er, wait a minute, I'm not advertising Grandma Georgia's Lard-o-hardtack, I'm throwing Mike the Mad Biologist another set of major props.

There's just no way I could've said it better myself. Mike is nailing this healthcare thing lately.

...the key point is this: people don't want exciting 'health insurance products', they want adequate care when they are sick. Also, how are we supposed to choose the 'right' healthcare...

...none of us have any way to evaluate if the insurance we have picked will provide the healthcare we need if something disastrous (or even mildly annoying) strikes. I have no idea if something bad happens (and there are many kinds of 'somethings bad') whether my plan will provide the healthcare I need. Would I have access to the specialists I might require? Which treatments would be covered, and for how long?

Tonight, I raise my scotch glass to you, Mike, for a succinct and elegant explanation of everything that's wrong with McCain's vision of healthcare.

Also, Chuck Dupree, a commentor on Paul Krugman's blog, has hit the nail on the head and driven it through the board with one swift stroke:

Add me to the list of those who can’t figure out why we’re talking about insurance. I don’t want insurance. I want health care, and I don’t see why insurance companies should be involved.

Caveat Emptor: Drugs and the Free Market

First reported (within my circle of sources and reading material) by PalMD of denialism blog, the FDA is cracking down on the sale of many unapproved "cancer cures" being sold online and elsewhere. This, in itself, is excellent.

It is also a fantastic example why trusting the free market to solve all problems is a completely bogus idea.

I always come back to healthcare whenever I want to talk about the free market. This is partly because healthcare is what I know; I am much more capable of talking about the prices of drugs (in particular) and medical services than I am talking about the prices of various other products because I'm surrounded by them. But, more importantly, the healthcare "market" is a spectacular example of an area where "natural market forces" are completely insufficient regulation.

The short answer for why this is is that the costs of healthcare services are not always clear up front, so there's no way to "comparison shop." You usually get treated and worry about how much it will cost later, especially in an emergency situation. The capitalist model of self-regulation requires consumers to be able to discern the cost of services in order for it to make any sense. How can you be an informed consumer if you can't evaluate the cost or the utility (worth) of goods?

Sure, this is true on some massive scale when we talk about hospital stays and surgeries, but the problem with those is that the only consumers who actually know what they cost are already bankrupt because of them (everyone else is insulated from the scary truth of the real costs thanks to insurance companies). But those are the big-ticket items of the healthcare world. And you might argue that in some cases that they're often essential to the point where price is no object, because most people would rather pay any amount of money than die. (They might regret this decision later when they're being suffocated by hospital bills, but few rational people are going to say "nah, let me die, saving my life will cost too much.")

So let's talk about small out-of-pocket expenses of non-urgent matters.

Buying drugs is, in many cases, like buying any other good. There exists genuine competition in the market, especially when we're talking about non-prescription items. Should I buy Alavert or Claritin? Benadryl or the "store brand?" Which pain reliever do I choose? The fact of the matter is that 99.9% of the time all of these goods are equal. It doesn't matter, from a medical perspective, whether you buy Claritin or Alavert. They're the same drug. The only reason consumers might prefer one over the other is because of advertising and brand recognition--this is a "Coke or Pepsi" scenario.

Most consumers know that Coke and Pepsi are equivalent products (more or less). Sure, they might have a preference for one over the other, and that preference might even stand up to blind taste-tests. But how many consumers really know that the "store brand" is as good as the brand name when it comes to drugs?

If marketing research is any indication, the answer is not many. In 2005, generic versions of OTC drugs made up only 23.4% of the market share. Conversely, generic prescription drugs made up over 75% of the market share. Hmm. Why might this be?

When filling a prescription, most pharmacies will automatically substitute the generic if one is available as long as the physician has indicated that such a substitution is acceptable. Some states (Massachusetts, for example) actually mandate substitution unless the physician indicates otherwise. It's easy to see why generic prescription drugs predominate the market. Many commonly prescribed drugs are more or less only available as generics; the brand names are no longer made or no longer carried by pharmacies (how many people really care about getting brand name Amoxil?). I think it is safe to say that one major reason generic drugs predominate in the prescription drug market is that patients are not actively involved in the brand versus generic decision. They are leaving the decision to someone who is more educated about the product they are buying. The doctor and the pharmacist both know (and will reassure the patient if necessary) that the generic is just as good as the brand for a fraction of the cost.

Letting your pharmacist substitute a generic to save you money is kind of like getting insider information on stocks or letting your broker decide where to invest your money. You're not stupid for consulting your broker. You're smart. You're using your broker's expertise to your advantage. He probably knows a lot more about the stock market than you do, and you will make more money if you let him help you.

There's also the fact that the price difference between brand and generic in the prescription drug market is pretty large. Consider lisinopril, a drug used to lower blood pressure, prevent recurrent strokes, and protect the kidneys of diabetics. Generic lisinopril costs about 50 cents a tablet. The branded product costs twice as much. Cholesterol-lowering simvastatin's (Zocor) generic is about $2 per dose. The brand is about $5. Does it really make sense to pay twice as much for something if you don't have to? Of course not. Consumers aren't stupid.

The short story is that about 75% of consumers, given what amounts to "expert advice," will pick the cheaper prescription drug product. So why do only 25% of consumers pick the cheaper generic when making an OTC drug purchase?

The same reasons why they would choose a branded drug if there weren't a pharmacist between them and their prescriptions.

Brand reputation. Perception of generics as inferior products--misconceptions about quality, purity, and efficacy. Prior "bad experiences" with a generic drug. Inability to pronounce the generic drug's name (yes, I'm serious). And people are suspicious about the origins of "store brand" drugs. I'm not sure where people think they come from--they're made in the same factories and held to the same manufacturing standards as the brands.

There's limited standardization in naming generic OTC drugs. Because drug chains can't rely on brand recognition the same way ("Claritin is for allergies, I saw it on TV") most generic OTCs have very...generic...names. "Non-drowsy allergy relief." "Non-aspirin pain reliever." "Stomach acid relief." I kid you not when I say that there are probably half a dozen products on a given pharmacy shelf that have some variation on the phrase "cold symptom relief" as their only name, leaving the consumer to decide which product to purchase.

If the consumer does not first consult an "expert" (the pharmacist), they is left using the same reasoning tools that affect their decision about brand-name drugs. Anecdotally, I would say that most consumers don't know the active ingredients in their preferred OTC cocktails. They know the color of the box. They know what the product is called. And, most important to the consumer, they know what worked last time they were sick. They want that again, whatever it was, even if it's the wrong drug for the symptoms they have this time.

(Walgreens is brilliant in this regard by shoving the "Wal-" prefix in front of all their generic names. I get a lot of people who ask me for Wal-itin. I don't work for Walgreens. Our Claritin generic is obviously called something else. Many of them don't even seem to realize that Wal-itin is Walgreen's name for their Claritin generic--they think Wal-itin is its own unique drug, brewed in some secret Walgreens facility.)

The price difference between brand and generic OTC drugs seems smaller, which is another major factor. A box of 50 Tylenol costs $6.50 at Walgreens. A box of the generic costs $4.50, $2 less. Normally, when someone offers you the same product at a lower price, you take it. The generic market should be totally destroying Tylenol sales, but McNeil Consumer Healthcare still sold $129 million worth of their flagship product, "extra-strength Tylenol tablets," in 2003. That doesn't include sales of the popular Tylenol PM, Tylenol Cold, or liquid Children's Tylenol. The sum for all these product lines from 2003 is about $242 million.

Think about that for a second. Consumers spent an average of $2 more per purchase to buy products with the Tylenol brand name so frequently that McNeil made $242 million dollars. And they did it for the reasons I've already mentioned above--or perhaps others. Marketing experts spend their whole careers trying to understand and capitalize on this stuff; my understanding of it is very basic.

This isn't like buying generic foods, where you might get something you don't like as much as the brand product. The generic drug industry is tightly-regulated by the FDA. You can't sell generic drugs that are inferior to the brand names, unless your definition of "inferior" is different from the FDA's. The drugs have to work just as well.

You could argue that consumers might be buying the brands over the generics because of factors other than how well they work as drugs. Sometimes brand name drug tablets have coatings or flavorings that make them taste better than their generic counterparts. Maybe the packaging is easier to open. Some people are legitimately allergic to certain dyes or additives that might be present in the generic that aren't in the brand (but this is extremely rare). But this probably wouldn't account for 75% of consumers choosing brands over generics.

No, the short answer to why consumers choose branded products when buying OTC drugs is that they don't actually have all the knowledge necessary to make an informed purchase.

Man, that was long-winded. Let's come back to the original point of the entry.

If consumers aren't making informed decisions about whether to buy brands or generics when making OTC purchases, who the hell thinks that consumers will be able to make informed decisions about how to treat their own cancer?

I'm not talking about violating patient autonomy here. Patients should never be forced to accept treatments against their will. Patients should talk with their physicians and discuss treatment options, then choose whatever they feel is most acceptable. But it is up to the doctor--who has many more years of education on the subject--to lay out the options. If the patient believes that there is an option that the physician has not mentioned, he or she should certainly bring it up.

But when physicians say "no, I don't think that's a good idea," the answer is not to go ahead and do it anyway. By all means, ask for a second opinion. You're entitled to one. But do not decide that somehow you are more qualified than a trained oncologist to choose your own cancer treatment. You are not. Ignoring the advice of experts to pursue the beat of a different drum to your own detriment isn't individuality. It's idiocy.

This is why holding up "freedom of choice" when talking about unproven (and often highly suspect) treatments for cancer or any other disease is a bullshit move intended to distract from the real issue at hand. Your doctor telling you that herbal tea will not cure your cancer is not oppression. Shutting down salesmen who commit fraud isn't oppression, either.

But in the worldview of the champions of truly deregulated free-market medicine, the consumer is granted a delicious variety false empowerment. You have the right to choose any treatment you want--even those that don't work. And if you choose treatments that don't work instead of those that do, well, caveat emptor. May the buyer beware. All sales are final and non-refundable. The only person you have to blame for getting scammed is yourself. And this is disgusting.

So go ahead. Fight for your freedom to get ripped off. The primary characteristic of the free-market is that it's self-correcting, right? Frauds will eventually be exposed and people will stop buying their products.

But how many people should be allowed to die before we say "enough is enough?"

Bizarro Health Savings Account

So the company I work for automatically lists items as "FSA eligible" if they are commonly covered by a flexible spending account for health purchases, sometimes known as an HSA. An HSA, if you're not familiar with the concept, is essentially a "bank" of money that you pay into (often with each paycheck). This money is tax-free, but you can only use it to pay for your medical expenses. Some plans allow your unspent dollars to roll-over at the end of the year, whereas others do not, leading to a last-minute spending frenzy. Most HSA plans allow you to spend the dollars you have on any health-related purchase, but there are always exceptions. As a general rule, it's safe to assume that standard over-the-counter products are probably covered, so those last-minute spending frenzies usually turn into people buying more aspirin and bandages than they are ever going to use just so that the money doesn't disappear unspent.

Anyway, at my store, both the register and the customer's receipt specifically note items that are eligible purchases; the customer can keep the receipt in the event that there is a dispute with the insurance company. This also allows the customer to just swipe their HSA card and have eligible items paid for while ineligible items remain unpaid. This saves the cashier from having to ring the items up separately if the customer wants to pay for some items that are eligible and some that are not.

There used to be an occasional problem where ineligible items would get rung up with an HSA debit card by mistake. Ultimately the consumer would get an audit from their insurance company bitching at them about trying to use their HSA to pay for bread and greeting cards. A recent update to the system actually prevents the register from accepting an HSA card for items that the register does not recognize as eligible; the cashier will get an error message saying that the customer needs to use a different form of payment.

So imagine my surprise today when Mucinex and Benadryl didn't ring up as FSA-eligible items. That was odd, and potentially noteworthy, but not that strange. It was conceivable that recent policies had changed to prohibit consumers from buying OTC items without a prescription.

Then Oscillococcinum rang up as FSA-eligible and I stared at the register screen in disbelief.

To make a long story short, "Oscillo" is a homeopathically-prepared dilution of the organs of a muscovy duck. It is a "200C" dilution, which is impressive even by homeopathic standards; the original formula has been successively diluted in a 1/100 ratio 200 times, meaning that the ultimate concentration of duck organ solution is 1 with 400 zeroes following it. This is four times the estimated number of molecules in the known universe, so the probability that the resulting solution contains any of the original "duck molecules" is basically nil unless somehow we have an entire universe filled with "Oscillo." Not that that's a problem for devoted believers in homeopathy. The preparation is touted by its manufacturer as a remedy for "the flu." You know, an illness that actually kills people from time to time.

So let's get this straight. According to the computer system at work, your insurance company is more likely to let you spend your tax-free savings on fake medicine than real medicine. In fact, the register would not let me charge a box of Benadryl to this guy's HSA because it considered the drug "an ineligible purchase."

See why I used the word "bizarro" in the post title?

The Price of Potency

Male readers, would you risk your life for an erection?

It seems like a bizarre (and personal) question, but there are patients that are more than willing to do it. They are so willing, in fact, that they will lie to both doctors and pharmacists to get their hands on little blue pills when it's the little white ones that are keeping their heart supplied with oxygen.

Viagra, Cialis, and Levitra belong to a class of drugs called PDE-5 inhibitors. PDE-5, otherwise known as phosphodiesterase isoform 5, is an enzyme indirectly responsible for maintaining the amount of free nitric oxide, or NO, in certain parts of the body. PDE-5's claim to fame is that it decreases the amount of NO in the vasculature of the penis in an area called the corpus cavernosum. NO causes blood vessels to expand, which in turn causes an erection. By blocking PDE-5, the overall concentration of NO goes up, making it easier to achieve erection--but not in the absence of sexual stimulus (typically, anyway). If you want some good anatomical diagrams, try this link, which coincidentally explains more or less exactly how these drugs work in more detail.

Nitroglycerin and other nitrates work on the NO system, too. All of these drugs either directly degrade into NO or indirectly release NO via metabolism in the bloodstream. Angina pectoris (chest pain) is caused by the heart receiving insufficient oxygen. In the treatment of angina, NO causing expansion of blood vessels allows more blood to flow to the heart. It also decreases the pressure in other vessels, making it easier for the heart to pump blood; because the heart is not working as hard, it needs less oxygen. The result is a reduction in angina symptoms.

Both of these drugs increase NO levels. NO dilates blood vessels. Can you see where this is going?

Yes, combining nitrates with PDE-5 inhibitors can result in so much dilation of blood vessels that blood pressure drops to dangerous levels. If pressure drops too low, vital organs (such as the brain) can become starved of blood--which means that they are also starved of oxygen.

This drug combination is therefore contraindicated, i.e., a totally bad idea--and the kind of thing that a doctor (or more likely a pharmacist) could get sued for prescribing/dispensing. Giving a patient on nitrates a drug for ED is putting the patient at serious risk. But I've encountered patients who were willing to lie to everyone within a five-mile radius--doctors, nurses, technicians, pharmacists--to get their hands on the blue pills (or yellow ones, depending on their preferred drug).

The whole scenario raises some interesting questions. Why are male patients willing to lie to their healthcare providers? Perhaps they don't really understand the risk. Perhaps they think they understand the risk, but they don't care. Perhaps they're being fed all kinds of mass-marketing and commercial nonsense about how they'll never be able to satisfy their lovers without Big Pharma's magic erection pills. ED is a serious quality of life issue for a lot of patients--those with diabetes are among the most commonly affected. But when we as a society are putting pressure on men to the point where they are willing to risk their lives to get a hard-on, something is wrong. And this pressure isn't new--the search for aphrodisiacs has been on ever since the start of recorded history. A biological imperative? A product of culture? Who can say for sure?

Advertising in Bizarro World

The other day I picked up a new copy of everyone's favorite pharmacy publication, DrugTopics. I generally like DrugTopics, except when they're running Zicam ads or otherwise uncritically promoting unproven treatments because the manufacturers were willing to pay for a page. The Zicam ads are annoying because they attempt to lend legitimacy to a product that has done everything conceivable to skirt FDA regulation--like calling itself homeopathic when in fact it contains measurable amounts of zinc. At a "1X" and "2X" dilution, a "recommended daily dose" of oral Zicam "cold remedy" tablets contains 80 mg of zinc. That's nearly eight times the typical dietary intake, and your average multivitamin contains about 10 mg as well. In essence, Zicam is about as homeopathic as Prozac, except that Prozac required FDA approval and Zicam didn't. Way to go, guys.

But this post isn't about Zicam. No, another advertisement caught my eye this time around--it was an ad for Luvox CR.

Luvox CR is a new formulation of fluvoxamine, a drug used to treat depression and obsessive-compulsive disorder. It's in the same general family as all the other SSRIs--Prozac, Zoloft, Paxil, Lexapro, et cetera. Granted, there are subtle differences between all of these drugs, but it's fair to say that fluxovamine (more or less) doesn't do anything spectacular by comparison; it is, in fact, one of the oldest SSRIs on the market.

Luvox CR, like many other drugs, is a follow-on drug intended to extend the patent life of a drug entity. Of course, follow-on drugs typically tend to come out a few years before a patent expires as opposed to a decade later, so Luvox CR is kinda missing the boat, but they're trying. All of this is acceptable, if shady, given the tendency of drug reps to push follow-on drugs like they're the greatest thing since sliced bread (and, of course, are totally worth paying $5 a dose for as opposed to the 50 cents the generic version of the old drug might cost).

Here's why I'm making the bizarro world reference. The advertisement's tagline was, and I quote: "NEW LUVOX CR: AN ANTIDEPRESSANT WITH NO GENERIC EQUIVALENT!"

I blinked in curiosity after reading these words. Was this supposed to be a good thing? Are reps supposed to approach psychiatrists, talk them up about the wonders of their new product, and wow them at the end with a concluding "best of all, this drug is going to cost your patients a fortune?" Who is this supposed to impress? I'm pretty sure the only people who think that "no generic equivalent" is a merit are the drug companies.

Or maybe these sorts of advertisements aren't ads at all--they're a warning to uppity pharmacists not to try doing stuff like "saving patients money" by "requesting lower-cost alternatives" and "cutting into pharma's profits."

Did I publish that where it was publicly viewable? Oooops.

Seriously. This is my biggest gripe about the pharmaceutical companies and their method of advertising. I can deal with them buying filet mignon for doctors. I can tolerate the magazine ads and even the occasional television spot, even if I think direct-to-consumer advertising does a lot more harm than good (no statistics, just impressions). What I can't stand is pharma advertising flaws as merits. "Our product costs ten times as much as our competitor's!" is something you would never hear touted as a positive in any other industry.

But hey, I'd much rather pharma play fast and loose with patent laws to try to squeeze a few more good years out of drugs that the FDA has thoroughly reviewed than "big woo" (sometimes the same companies, for that matter) play the get-out-of-jail-free "it's alternative medicine" card. After all, big woo has to slap the quack Miranda warning on all their products.

It's a strange day and age when "costs more!" and "isn't proven to work!" are somehow twisted to be signs of a good product.

A Brief Personal Update: Plus, Insulin By Mouth? (Kinda)

After several panic-filled weeks of last-minute cramming for final exams, N.B. is finally "free" for the summer (aside from all those lick-and-stick hours at the local pharmacy where he earns his keep). The goal at this point is to finally find things I enjoy doing--like blogging--instead of shoving medicinal chemistry into my head so that I can pass the semester-end exam.

It also gives me time to do less academic (but arguably no less cerebral) things to do, like finally beating Metal Gear Solid 2 on the "extreme" difficulty. Preferably without using hundreds of continues. No, I haven't done it yet, but it's a by-end-of-summer goal.

In any case.

This particular story apparently isn't breaking news--and if you've been following it, it's a saga that has dragged on for several years, reportedly with the intervention of Big Pharma trying to shut down Little Biotech, or at least buy them out. But here's the exciting news for patients and investors alike. An oral insulin spray is still in development and has apparently performed well in trials. The medication is approved for use in Ecuador and India, and it is currently undergoing phase III trials in the U.S., suggesting that we may see some sort of release in the states in the next one or two years.

Buccal administration is a complicated-sounding way of giving medicine by having it absorb through the cheek. The cheeks and area underneath the tongue have a rich blood supply and fairly thin barriers between the bloodstream and the outside world, permitting specially-formulated drugs to cross easily. While a lot of buccal drugs are used for their local effect (like anesthetics), some are intended to effect the whole body, like the opioid pain-reliever fentanyl, which is available as what amounts to a sucker.

Another major advantage of buccal administration is that it bypasses both the stomach and the liver, preventing the drug from being broken down before it enters the bloodstream (in the case of the liver, this is called first-pass metabolism). Protein drugs, such as insulin, cannot normally be taken by mouth because the stomach and intestine will digest them like any other protein, rendering them inactive. To prevent insulin from being reduced to useless amino acid bits, it must normally be given by injection.

The reason inhalation was considered as a route of administration for insulin was because it, too, bypasses the breakdown that takes place in the stomach. Theoretically, the rectal route partially bypasses first-pass metabolism (it actually depends how far up you insert the suppository), but I can't imagine rectal insulin would be very popular, and there are other complications.

For the pharmacologists in the audience, now I'm trying to imagine what sort of formulation barriers might exist to insulin suppositories. Base incompatibility? Temperature/storage problems? I've never even heard of a protein drug being given by that route. But I digress.

The product that the article I linked is talking about is a spray--think something like breath spray--that is applied to the inside of the cheek. The spray would be metered to provide a precise dose, but fine-tuning might be difficult unless the spray can be "dialed" to spray different amounts of insulin. The details are still fuzzy, but the research is still very exciting.

Patient compliance--the ability and willingness of a patient to properly use his or her medications--is a huge obstacle for patients with diabetes. Anything that makes administration of insulin easier for adults and children alike is definitely a good idea, assuming of course that there are no long-term drawbacks and that the system is practical (inhaled insulin turned out not to be). I'm looking forward to seeing where this research goes.

Just Pissing It Away

It's been quiet in my corner of the blogosphere, but I lay the blame squarely on the fact that my latest round of exams has kept me extremely busy. Ths plus side of all this is that I get to come back to lots of news, all ripe for comment!

Like this article published today analyzing a couple studies from early 2000 about certain drugs prescribed for high blood pressure being potentially tied to bone loss, particularly in older men.

Most of the time, our sound bite-focused media doesn't get the whole story out there. This article is no exception.

Diuretics are commonly called "water pills," particularly by older people. I really, really hate that term. It isn't even remotely appropriate for describing how diuretics function. I suppose that the analogy comes from the idea that drinking more water causes increased urination, and taking diuretics causes increased urination; hence, diuretics are "water in pill form," except that that totally fails to explain how they work to lower blood pressure. Normally I don't think it's necessary for patients to know the mechanisms of action for the drugs they take--such details are excessively complicated. But we strive to explain things in the simplest way we can without sacrificing accuracy. Antidepressants, for example, are said to "balance or correct problems in brain chemistry." This is simple, but true at the base level.

Diuretics don't add anything to your body, and they certainly don't hydrate you. They have varying mechanisms of action, but what they really do is increase the body's excretion of certain elements that float around in the body in ion form. Sodium, potassium, and calcium are three good examples--they are commonly called "electrolytes," especially if you like reading the labels on your sports drinks. Generally, sodium loss is desirable in patients with high blood pressure. All of these ions must be present in proper concentrations for the body's various functions to work properly. Too much and too little are both bad. Diuretics are a convenient way to get rid of excess electrolytes.

The diuretic the article is talking about is furosemide, though there are other diuretics in the same family that have the same effect. Furosemide flushes out sodium, potassium, and calcium by preventing the kidneys from re-absorbing it at a specific point (the loop of Henle, if you're curious). Many patients on furosemide are also prescribed potassium supplements to counter the potassium loss. The calcium loss is not as frequently addressed, but it really should be; then again, most people don't get enough calcium anyway.

But saying diuretics in general are responsible for worsening bone loss is not only alarmist, it's false. Hydrochlorothiazide, or HCTZ, actually results in calcium retention. Sometimes this is a problem, as it can cause calcium levels in the blood to get too high. But for some patients with high blood pressure who are also at risk for osteoporosis, HCTZ is a great drug; it helps them retain extra calcium, improving bone density! This doesn't mean that everyone at risk for osteoporosis should be on HCTZ; increasing dietary calcium and vitamin D are a much better idea. But when treating patients with high blood pressure, it is often best to use drugs that "kill two birds with one stone." Likewise, it doesn't mean that patients at risk for bone loss shouldn't get furosemide. This is what trained physicians and pharmacists are for--evaluating the complicated mess of risks, benefits, and drug interactions that make modern medical therapy so difficult to manage.

And that's the bottom line--medicine is complicated. One 200-word article in a newspaper is never going to explain all the ins and outs of any particular treatment or drug; that's why scholarly journal articles are long, detailed, and extensively referenced. So consider very carefully where you get your information; chances are that if it was packaged for the general public and sold at the newsstand, you're not getting the whole story.

Alarmist Media Soundbites Annoy Pharmacy Student

Let it be known that there are few ideas that cannot be expressed in a more entertaining way by using AP-style headlines.

There's been a lot of talk about how common medication errors or overdoses occur in hospital settings, particularly in children. A good bit of this can be attributed to the recent heparin mix-up involving Dennis Quaid's children. This particular error, fortunately, caused no deaths, unlike some previous errors in Indiana a year or two ago. The Quaids have every right to be upset--and they have every right to campaign to make the issue more visible. Medication errors are serious business, and hospitals should do everything in their power to prevent them from happening.

That said, the issue is being way over-hyped by the media.

According to the first link, one in fifteen children admitted to a hospital--about 7.3%, or 540,000 children across the United States each year--is harmed by a medication error. These are the figures that are being pitched around by the media in multiple places.

But these figures are misleading and alarmist. What a shock! Here's the study they're citing.

Part of the issue is the definition of an adverse drug effect. According to the Washington Post:

More than half of the problems cited involved overdoses or allergic reactions to painkillers.

The "or" in that sentence complicates the issue, but here's a simple statistic. The two biggest classes of pain medication are NSAIDs like ibuprofen and opioids like morphine or codeine.

True opioid allergy is exceedingly rare. In fact, less than 1% of the population is estimated to be allergic to opioids. Likewise, only about 1% of the population is estimated to be allergic to NSAIDs (though NSAIDs may precipitate problems in some patients with asthma).

This means that if the numbers reported are accurate and 11 out of 100 children hospitalized experience an adverse effect, only one of those is truly allergic to the drug in question--and there's nothing that can be done about that, short of avoiding the drug. Unfortunately, patients without a history of an allergic reaction are not going to discover the allergy without being exposed to the drug. This seems largely unavoidable. So what about the other ten kids? If the Post is correct, all of them recieved some kind of overdose.

Let's take a look at the actual study:

Twenty-two percent of all adverse drug events were deemed preventable...ninety-seven percent of the identified adverse drug events resulted in mild, temporary harm. [emphasis mine]

Mild, temporary harm? What kind of harm?

The most common adverse drug events identified were pruritis [itching] and nausea, the most common medication classes causing adverse drug events were opioid analgesics and antibiotics

Huh.

Even patients not truly allergic to opioids may react with what is called a pseudoallergy. Where a true allergic reaction is a result of inappropriate overactivity of the immune system, pseudoallergy reactions are a result of sudden histamine release, causing flushing, itching, sweating, or hives. This is a well-documented side-effect of opioids. Is it totally preventable? Sure--by not giving opioids! Of course, this is why using the lowest effective dose of a drug is always a good idea--unlike true allergies, opioid pseudoallergies are dose-dependent, so higher doses increase the probability of a reaction. The good news is that antihistamines can be used to reverse the majority of these symptoms.

Antibiotics, conversely, wipe out friendly bacteria in the digestive tract, which is commonly accepted to be a cause of antibiotic-induced nausea and diarrhea. Other factors include the direct effect of the drug on the digestive tract, but decimating gut flora isn't doing anyone any favors. Some antibiotics are worse than others, but nausea is extremely common with antibiotic therapy--and, again, there's basically nothing that can be done about it.

At this point, the question should not be "how many children suffer adverse drug reactions?" This statistic is too simple to have any predictive power, especially when including mild or easily reversed side-effects that are extremely common (and predictable) or associated with the use of particular drugs. We should be more concerned with medication errors than minor adverse reactions. A patient getting a thousand-fold overdose of heparin is serious. A child getting a stomachache as a side-effect of antibiotics is not. So let's turn the statistics around--only 3% of adverse reactions were serious. A full 97% were mild and/or reversible. That sounds like good news to me!

I've come to expect that the media is going to spin everything they report to make it sound infinitely worse than it actually is--bad news sells. But the last thing we need is parents panicking about medication errors and being afraid to take their children to the hospital. Vigilance on the part of both parents and healthcare providers is good. Panic--and subsequent distrust--is not. Distrust of medical professionals is one of the main factors that turns patients to supporting woo.

And since I can't resist plugging my own profession, let's not forget that well-trained pharmacists are crucial players in reducing medication errors.

A Total Waste

According to a recently released report, lack of health insurance results in higher death rates.

A report issued Friday by Families USA, the national organization for health care consumers, concludes that nearly three people die each day in North Carolina because they don’t have health insurance.

The Families USA report says people without health insurance are more likely to delay seeking care because of the high bills, which means disease such as cancer are diagnosed at a later, more deadly stage.

Really?

I believe that this sort of thing speaks for itself. The cost of healthcare is astronomical--and it is quite simply unaffordable for the uninsured. By contrast, the insured in this country have an exceedingly poor grasp of the real cost of medical treatment, simply because they've been insulated from it by copays and percentages. Most people have some tenuous grasp on the idea that treatment for life-threatening illnesses is costly--treatments for cancer, for example, or any major surgery. But if outpatient pharmacy is any indication, most patients think that $50 is a "really expensive" drug product and they start complaining about how their insurance clearly didn't cover anything.

For some reason, telling them that the real cost of the medication is $250 doesn't change their tune.

What more can I say? I live in one of the richest countries in the world, but we have the poorest health outcomes per dollar spent. Despite the fact that America is the "first-world," people die from treatable illnesses because they can't afford to seek medical care until it's too late.

Flagellating a Long-deceased Equine

How much more of this are we going to have to take?

Vaccines do: Prevent potentially fatal or crippling diseases.

Vaccines don't: Cause autism.

Seriously. Only in a wealthy, priviledged country like America do people have the time and resources to blame medical care for ruining the lives of their children. People in third-world countries will quite frequently do anything to get medicine, vitamins, or vaccinations to prevent or treat polio, rickets, malaria, or any number of other diseases that have been effectively eradicated in the first-world--eradicated thanks to medical science, not ambulance-chasing lawyers seeking thimerosal settlements.

Let me restate that. People are spending hundreds of court-hours and millions of dollars in legal fees trying to prove that a medical intervention that people across the globe are dying to get their hands on harmed their children.

Is this really about protecting children? Or is it about reaching into corporate America's deep pockets and snagging a piece of the autism settlement pie with your sticky fingers?

Abused Vocabulary #2: Chemicals? In My Child's Hair?

I cringed today during one of my lectures.

The instructor was discussing pediculosis, otherwise known as lice infestation. Lice are a recurring nightmare for public places where children gather in large numbers--daycares and schools come to mind. I have vivid memories of the school faculty lining us up in the hallways outside the nurse's office for occasional lice inspections.

She went on to mention--but not necessarily recommend--"natural" treatments for head lice. Apparently, olive oil, tea tree oil, and mayonnaise, and various other products are occasionally used as alternatives to "chemical pesticides."

What threw me was the professor's specific quote: "Well, some parents are going to use these because they don't want to put chemicals on their children."

Huh. I don't know. I would be terribly concerned about rubbing oleic acid, palmitic acid, stearic acid, and lineoleic acid into my child's scalp, wouldn't you? I mean, they're acids. Acids are corrosive, dangerous substances that can dissolve rocks and metals!

Except that they're fatty acids. There's a big difference between hydrofluoric acid and oleic acid, especially considering that the latter is the major component of olive oil.

The point is that anything can sound scary if you describe it the right way--consider the dihydrogen monoxide issue. (For those who don't immediately get the joke, dihydrogen monoxide is water). And it drives me nuts when people who are supposed to be scientists--or worse, educators--haphazardly use the word "chemicals," apparently validating the public's irrational fear of the very word, a word associated with harmful, "unnatural" things like benzene and turpentine instead of water, salt, and sugar.

Of course, the joke is on them. The active ingredient in RID is made from crysanthemums.

A Remarkable Lack of Self-awareness

A tragic story released today by the Chicago Tribune really makes you wonder about people's abilities to critically examine their own point of view--even when lives are on the line.

Police are investigating an 11-year-old girl's death from an undiagnosed, treatable form of diabetes after her parents chose to pray for her rather than take her to a doctor...

...the girl's mother, Leilani Neumann, said that she and her family believe in the Bible and that healing comes from God, but that they do not belong to an organized religion or faith, are not fanatics and have nothing against doctors. [emphasis mine]

Are you sure about that?

According to the article, the girl had not been to a doctor since she was three (at least she got routine immunizations). Relatives, including an aunt, called the authorities to report that the little girl's life was in danger because her parents were refusing to take her to a hospital and were instead trying to heal her with prayer.

The interesting thing about the case is that, like so many others in the same vein, the legal route of investigation is whether or not the parents were negligent in caring for their daughter. The authorities (and most sensible people) will most likely conclude that not taking a comatose girl to a hospital qualifies as negligence.

The parents, on the other hand, are going to argue that "they did everything they could." They wanted their little girl to live; this was not negligence in the sense that they were unconcerned whether she lived or died. The father attempted to perform CPR. If the family's statements are to be believed, they did not want to see her die.

If the parents truly believe that they did everything they could, one of two things is the case. They were incompetent or they were brainwashed.

I'll leave which one up to the reader to decide.