Thursday, November 29, 2007

Blog Around the Clock

A blogger by the name of apgaylard posted this excellent bit about homeopathy yesterday, and it's a shame I didn't see it sooner. Through some remarkable detective work, he managed to dig up several studies that were done in an attempt to refute complaints by homeopaths that the results of some homeopathy studies were "secret." These studies, particularly strong evidence against homeopathy, were supposedly hidden from homeopaths--perhaps they suspected that they weren't as damning as they thought, and that homeopathy would finally get its due if they were only exposed to the light?

Naturally, that wasn't true.

Also, a big thanks to The Bad Idea Blog for the link to my entry about Hoodia. In return, I'll have to plug his thoughts on upcoming book-turned-film The Golden Compass, a film that has raised a remarkable amount of controversy among some acquaintences of mine and spurred some very interesting discussion. Bad's blog is excellent and I regret not reading it more frequently!

Pharmaphobia and Placebophilia

I really love compounding novel or at least semi-novel words from roots and stems. Perhaps I should consider a serious study of German.

If you whip out your copy of the Diagnostic and Statistical Manual of Mental Disorders, you'll see that a specific phobia is defined as an irrational fear of a specific object, situation, or environmental factor. Exposure to the phobic object typically produces classical symptoms of a panic attack--hyperventilation, increased heart rate, and feelings of anxiety. The phobic patient knows that his or her fear is irrational, but cannot overcome the fear through rational thought.

I've never met anyone who I would classify as a "pharmaphobe" in the sense that the sight of aspirin tablets caused them to collapse into a pile of terrified, quivering flesh, though it would certainly be interesting from a clinical perspective. No, what I'm talking about is a set of reactions to drugs and drug therapy that are associated with a mixture of misconceptions that many people I talk to seem to have. I have definite experience with people who say that they really don't like taking drugs. "Side-effect" is a really dirty word in the pharmacy business; patients want to know about them, but doctors and pharmacists don't want to scare their patients out of compliance. Part of effective patient counseling is knowing what side-effects a patient actually needs to be concerned about and communicating the issue of risks versus benefits.

I can sympathize with a desire to avoid drugs on some level. Taking medication is an acknowledgement that you are sick. I've heard stories about patients with chronic illnesses like high blood pressure or diabetes not taking their meds becuse it will mean facing their disease. They would much rather ignore it and hope it goes away instead of worrying about taking a lot of drugs. Patient compliance with a treatment course is a huge factor; drugs don't work if you don't take them. And when patients have to swallow a dozen tablets or capsules a day, if not more, many of them get discouraged and feel as though they have to structure their lives around taking their medication. There's a reason that once-daily dosing is preferred by both physicians and patients alike; it results in better outcomes due to increased compliance. Medical professionals sometimes call this "pill burden."

Likewise, it isn't necessary to take drugs for every ache. Not every headache calls for painkillers. Simple nausea, perhaps due to indigestion, will probably run its own course before any oral medication is going to have time to enter the bloodstream. A day with a stuffy nose doesn't necessarily require oral decongestants or nasal sprays to rectify.

The irony is that there's some overlap between the group that brandishes a holy symbol at your friendly pharmacist and the group that demands Benadryl after every sneeze.

Many people who have problems have a psychological need to feel like they're doing something to fix them, and sometimes they apply the same logic to their health. If something doesn't feel right, there must be a cure, and every moment they spent not seeking it is wasted in idleness. These people simply will not take no for an answer. They came to the pharmacy to buy something that will make them feel better, and they're going to find something, no matter what the pharmacist says. At some point, many of them eschew logic, close their ears, and leave us in the profession wondering why they ever asked for our opinion if they're already so knowledgeable about what will help with their symptoms. They really want to buy something, as though the act of purchasing a product will help more than anything else.

I had a conversation with a man yesterday of this very nature. He complained of a sore throat. No other symptoms. After further assessment of his condition and history, I recommended he try some acetaminophen.

"But I've already got that at home," he said, "and I wanted to get some Coricidin. Coricidin works well for me, and I have high blood pressure."

I've already talked about how much I hate marketing in medicine. It steers people in the wrong direction. It doesn't matter what's on the front label; that information is not regulated whatsoever. You have to turn the box around to get any useful information. I don't remember which product the man selected; there were probably five or six options. I think he chose the only one containing no pain reliever whatsoever and would not be dissuaded from his choice. He made his decision based on what seems like reasonable logic: I felt lousy before, I used this product, I felt better. Brand-name marketing is wholly reliant on this idea of recognition and loyalty. It wouldn't be so bad if it didn't obfuscate the issue for layman consumers thats what's in the tablets is everything and what's on the box is irrelevant.

But sometimes you can give no recommendation, or the patient is already doing everything they can. The common cold is the best example. I'll go through a patient's symptoms and necessary medical history. Once I have the information I need, they don't like any of my suggestions. "Antihistamines make me sleepy." Sometimes they're already taking a product containing everything I could logically recommend. "I'm already taking Advil Cold and Sinus, I thought maybe you could suggest something else."

(As an aside, the number of people who ask me for "non-drowsy Benadryl" is kind of staggering. Diphenhydramine, the primary ingredient in Benadryl, is also the primary ingredient in almost all OTC sleep aids. It's kind of like asking for non-alcoholic Everclear.)

That's when they get disenfranchised with what I have to say and start taking medical advice from their mother-in-law, their roommate, the internet, Oprah, whatever. I call it "second opinion syndrome." It might be legitimate to ask for a second opinion if you're considering major surgery. We're talking about the common cold. And it's not that they want another medical opinion--they want any opinion, as long as it's what they wanted to hear in the first place. Yargh. How can you compete with that?

Sometimes people die because they turn to so-called "alternative medicine" instead of scientifically-valid treatments, but most of my patients are fairly far from that stage. No one is (likely) to die from taking vitamin C to stave off a cold or because they wasted money on Airborne. And you get two kinds of people who lust after those boxes of Emergen-C on the pharmacy shelves: Those who "hate drugs" and would rather "take something natural" and those who have exhausted all the other plausible options for treating a cold and are just desperate to feel better faster. So desperate, in fact, that they are willing to spend $20 on Cold-FX or other similar remedies. One of the big claims of homeopaths in particular is that their remedies are less expensive than mainstream medicine. That's kinda funny, seeing as how 30 lozenges of Cold MD and Oscillococcinum, cost a lot more than generic diphenhydramine, which will dry out cold symptoms and might even help a sufferer get some sleep. I think I got a 100-count bottle for like $12 over the summer and still have a ton left.

The first group is the extreme pharmaphobes. They are so terrified of drugs, drug companies, doctors, and pharmacists that if you see them in the pharmacy it's because the GNC is closed. The FDA and the government are in league with pharma and poisoning babies because they're too proud to admit that all forms of cancer can be cured if you just IV push enough vitamin C. They just came from their naturopath and are on the way to the chiropractor and couldn't be bothered to drive to the health food store. They are extreme granola people. This is kind of a funny picture, but I think these types are pretty rare unless you live in California.

The second group are the pseudopharmaphobes who will drop off their prescription, pay for it, discuss it with you, and then start whining about how having to take drugs is ruining their life. I would go out on a limb and suggest that diabetes or hypothyroidism or depression or perhaps chronic pain are considerably worse, but I would probably get fired.

And the third group are the placebophiles.

I was talking to a friend online the other day about how much it bothered me when patients asked for advice and then promptly ignored me. He agreed that this sounded annoying. Since we were discussing the common cold, his response was, "yeah, the only thing you can really do about that is take vitamin C, right?"

No, not really. His idea was one step from correct. Like most well-informed patients, he knew that antibiotics were worthless against the common cold, it being a viral illness. But he still held the pervasive idea that the common cold was preventable or treatable with vitamin C--not because of his lack of intelligence, but simply due to the issue that "vitamin C treats colds" is a very commonly cited health misconception. I provided him with some information to read on the subject, which he found interesting. It was at that point when he said something that struck me.

"Huh," he said. "Well, it's not going to hurt anyone, so I don't see why people shouldn't just take vitamin C anyway. I don't have a problem with 'gentler' medicine as opposed to drugs that have side-effects."

I'll direct you elsewhere regarding the error of his statement. What I think he inadvertently hit upon is the idea that some people really like placebos. Not even in the sense of a sugar pill containing no active ingredient, but in the sense of taking some medication, even if it's one totally unrelated to their illness, like the Coricidin man. They don't care if a treatment works or not. In fact, if the treatment is going to be ineffective but is unlikely to do harm, they'd rather not know about its lack of good efficacy data, a reaction I get frequently from patients asking me about zinc lozenges, which might have some efficacy but probably aren't worth the money or the unpleasant taste. We report, you decide. What's important to most of these patients is feeling like they're doing something about their illness, whether it's effective or not. They feel better, psychologically speaking, which probably improves things for them at least a little. In fact, there are so many psychological components to why people choose to use certain treatments even if they know they're placebo treatments that I could probably write indefinitely on the subject. Which raises an interesting question; is a placebo a placebo if a patient knows it's a placebo? I think that, through the amazing power of doublethink, it still can be. My girlfriend actually tries to "induce the placebo effect" whenever she takes medication: "I know this medication will work, and by thinking about the fact that I know it will work, I can make it work better." That probably isn't true in the strictest sense, but having confidence in a chosen therapy certainly makes you feel better about using it and can relieve emotional stress.

So both supplement-popping health nuts and your poor guy with a cold who just wants to feel better have something in common. They both want to feel like they have control. The idea is terribly appealing for some; we can prevent ourselves from ever becoming ill if we only do the right thing and are on our "best behavior" from a health perspective. We can all live forever if we only get the right vitamins. And health practitioners, not wanting to trample patient autonomy or turn off the potential benefit of the placebo for self-limiting conditions, are tight-lipped because they're deathly afraid they'll do something that will ultimately have a negative effect on patient outcomes.

Until the medical industry can literally cure every known illness with simple treatment regimens, placebophilia is here to stay. It's a part of the human psyche.

Wednesday, November 28, 2007

Myths, Beliefs, and Cancer

This article on Highlight Health is absolutely amazing. It's succinct and brilliant; I highly recommend it.


Near the beginning of the month, the FDA approved Zyrtec-D for over-the-counter sale in the U.S.

Rx-to-OTC conversions are always a matter of great interest for pharmacists and patients alike. Prilosec OTC floated around the FDA for a long time because the FDA was uncertain as how to to label it for patient use, eventually settling on the current information. And one of the other big non-drowsy antihistamines on the market, Claritin, was actually moved to OTC as a result of a petition by insurance company WellPoint; apparently, they got tired of paying for it. Prescription antihistamines are a huge portion of the pharmaceutical market share, totaling over $4.3 billion in 2001.The price of Claritin dropped over 70% after becoming OTC, and generic versions soon followed. Zyrtec's patent supposedly expires this December, so we may see generic versions sometime soon.

So what's the big deal?

First, for what it's worth, the U.S. is kind of behind the curve on this. OTC Zyrtec has been available in Canada for a while now under the brand name Reactine.

Second, most comparative studies suggest there is no clinical difference between newer antihistamines, though side-effects may vary somewhat. Some other studies say one or the other is better; many patients I talk to swear that Claritin is ineffective but that Zyrtec or Allergra works wonders. Aside from patient preference, the only major difference between these drugs is cost. And while the availability of Zyrtec as a competitor might drive down the cost of Claritin, generics have already done that considerably. I purchased 240 generic loratadine (Claritin) tablets last spring for about $30, which is what my insurance company wanted me to pay for prescription Zyrtec each month (retail price being something like $74). Eight months of therapy for the price of one. Not bad.

As an aside, it's kind of weird that only Zyrtec-D is going over the counter. Zyrtec-D, like its cousin Claritin-D, contains both an antihistamine (cetirizine, the generic name for Zyrtec) and the popular decongestant pseudoephedrine (PSE), well-known as being the primary ingredient in methamphetamine production. I expect "plain" Zyrtec to follow eventually, and this has little significance, but it's just an observation. Strictly speaking, all the studies I've cited were done with antihistamines alone, but since both products are available in combination with PSE, the comparisons are still valid. While both antihistamines may offer better relief to stuffy nose sufferers across the world when combined with PSE, the effect of PSE isn't going to change significantly by being paired with an antihistamine, so comparing the antihistamines directly should be sufficient. It is worth noting that Zyrtec theoretically causes slightly more drowsiness than Claritin, but it's conceivable that the mild stimulant effects of PSE will counteract that. Maybe that's the reason plain Zyrtec isn't going OTC yet. Who knows.

One of the pharmacoeconomic impacts of insurance companies pushing Claritin OTC back in 2002 is that many state Medicaid programs stopped paying for non-sedating antihistamines because patients could now get them over-the-counter. Medicaid patients who found Claritin ineffective or whose physicians prescribed other drugs were frequently out of luck, and at least a few patients were probably still unable to afford Claritin, leaving them totally out to dry. It's actually pretty likely that, at least initially, consumers will pay more for Zyrtec-D when it goes over-the-counter than they do now. Insurance companies, conversely, will save money by not reimbursing patient costs for the drug. The price for uninsured patients should drop sharply, though this doesn't necessarily mean Zyrtec-D will be the best deal available. Practically speaking, Rx-to-OTC switches tend to make self-treatment more convenient and increase patient access to medication at the drawback of increased costs for all but the uninsured. Where is that money going? Insurance premiums are still on the rise; I'll believe that making Zyrtec OTC will reduce premiums by lowering the expenses of insurance companies when I see it happen with my own eyes.

Expect to see a lot of advertising for "new" Zyrtec-D, now available OTC. Don't expect it to revolutionize the self-treatment of allergies. At best, maybe the "antihistamine wars" will make it cheaper for all of us to keep from sneezing around cats.

Tuesday, November 27, 2007

The Acetaminophen Blues

Nearly everyone I talk to has a favorite pain-reliever. It isn't always a branded product, and I'd love to conduct an informal survey or track customer buying habits in my store as I couldn't find any data I wanted online, but right now all I have are informal observations. Most of the people I talk to take either ibuprofen or acetaminophen for everyday aches and pains, with a few opting for Aleve or combination products like Excedrin. And they quickly become annoyed if they can't find their favorite product; Excedrin PM and Tylenol PM are identical except for the packaging, and one customer I spoke with yesterday was very certain that there was some other product called Excedrin Migraine PM that was nowhere to be found on our shelves.

Then there are the oddball homeopathy fans who spray diluted capsaicin into their noses when they have a headache. Apparently they even have a formula for prostate trouble. I am having an incredibly difficult time wrapping my brain around the idea of spraying hyperdiluted pepper oil and saw palmetto into your nose because it's stuffy and you're coincidentally having trouble urinating.

I could probably go on about what's wrong with the aforementioned products all day, but that would be silly when I can bring up something that's actually useful.

A lot of patients are a little confused on the whole anti-inflammatory issue. Most of them assume that NSAIDs, the most common OTC anti-inflammatory drugs for oral administration, are automatically better at relieving pain than acetaminophen (or paracetamol if you're on the other side of the pond). And that simply isn't true.

Acetaminophen, hereafter referred to as APAP, is a real miracle drug in a lot of ways. In fact, its mechanism of action is not perfectly understood. It provides pain relief via a slightly different mechanism than NSAIDs; like NSAIDs, it blocks the effect of substances called prostaglandins. Prostaglandins have various short-duration effects on tissues, one of which is to sensitive nerve endings to pain stimuli; in essence, prostaglandins lower the threshold required to make the neurons associated with pain fire. NSAIDs prevent prostaglandins from being formed entirely by blocking the effect of an enzyme called cyclooxygenase, or COX. APAP appears to block prostaglandin synthesis, but not in peripheral tissues; at least one theory suggests that APAP has an effect on the same receptors that the THC in marijuana. I say APAP is a miracle drug because it does this without the side-effects that NSAIDs have, asprin included, and it provides equal pain relief to aspirin milligram for milligram. APAP does not damage the stomach, thin the blood, or affect kidney function. It's very safe at appropriate doses, non-addictive, and it's even okay to use in pregnancy!

Because NSAIDs block the formation of prostaglandins by COX at the site of injury, they provide both relief of inflammation and pain. But for many minor causes of pain, an anti-inflammatory component is unnecessary. At least one study in the American Journal of Sports Medicine suggested that anti-inflammatory effects were not necessarily especially valuable in muscle injuries. In fact, the study compared simple APAP with Merck blockbuster Vioxx and found APAP to be just as effective without causing the poor atheletes to keel over from strokes! (Just kidding about the strokes. Sorta.) And for patients with mild-to-moderate pain due to osteoarthritis, the American College of Rheumatology, recommends APAP as first-line treatment unless significant inflammation is present.

NSAIDs are commonly cited by patients as being better for pain relief, and even a lot of pharmacists will immediately reach for the ibuprofen when it comes to recommending a painkiller, but the pain-relieving component is ultimately more important in many cases than the anti-inflammatory component. And for that, APAP is often just fine. APAP isn't necessarily the best drug for all pain relief; that's something to discuss with your personal healthcare provider. But it's often a good first choice for mild pain, especially since the inflammatory response is a part of wound healing. It's cheap, too, even compared to other pain-relievers, perhaps aside from uncoated aspirin tablets.

Monday, November 26, 2007


Here's a little fact that's good for a laugh. A popular herbal supplement for weight loss, commonly referred to as Hoodia, is made from a rare cactus that grows in the Kalahari Desert of South Africa.

Given the known mass of Hoodia gordonii plants in South Africa, and the known listed quantities of plant extract on all the products available on pharmacy and health food store shelves, there is apparently more Hoodia floating around in dietary supplements than there is in South Africa.

I'll say that again. If the labels on these supplements are totally accurate, there is a great deal more Hoodia crammed into capsules than there is growing in the Kalahari. Where did it come from? Are the supplement companies growing Hoodia cacti in farms somewhere?

(Hint: It's a lot more likely that they're lying on the labels.)

It's Only Natural

Well, after a week of cushy home living where the staples of my diet included artisan asiago cheese bread and home-cooked garlic mashed potatoes, it's back to the college student life where breakfast, when consumed, consists of sausage biscuits and a can of coffee-flavored energy drink. For the intrigued, Java Monster is pretty tasty, about on par with the Starbucks canned iced coffee but in larger cans for the same price.

Which brings me to the point of today's entry. My hasty student "breakfast" sounds terribly unhealthy. A cured frozen meat product loaded with salt and preservatives served on--gasp--a croissant roll made with bleached flour? A beverage loaded with glucose, sucrose, and even a touch of sucralose--a compound that contains chlorine, for crying out loud? Surely I could've done better, perhaps a low-glycemic index organic whole-grain bagel with just a touch of ultra lite-omega-3-heavy spread and a glass of fortified organic soy milk?

I dunno. The latter breakfast sounds pretty terrible to me from a "food enjoyment" perspective, and I'm not sure whether it'd be any "better" for me in the long run. Maybe not everyone agrees on the taste issue. And that's where I'm headed with this; the whole issue is one of personal preference.

I was having a conversation with an acquaintence at a social gathering about a week ago; she mentioned that she'd been having some "girly problems" because our table consisted of myself and three other women. I don't think she expected me to take interest in this sort of thing, but apparently she'd just switched oral contraceptive regimens lately and she'd had a terrible reaction to the new one, namely a generalized skin rash. Her husband had been surgically sterilized some time ago; her reason for taking OCs was to control other problems, namely what sounded to me like polycystic ovarian syndrome. She was very concerned that taking "artificial" hormones was going to increase her risk of dying of cancer, but she admitted that she didn't know much about the subject and that no one had gone to any length to explain it to her. I forwarded her a couple articles, including one from the Guardian about how OCs decrease long-term cancer risk in women.

When she brought up how she wished she didn't have to take "artificial" hormones, I asked her what "natural" hormones were. "I'm not entirely sure," she replied, "I guess the ones in my own body." What she really seemed to mean was that she didn't want to take extra hormones, because she didn't realize that ethinyl estradiol differs from estradiol, the most common and potent "natural estrogen," by only one chemical group, the triple bonded carbons at the 17th position (in the upper right on the image). Estrogen isn't a single compound; it's a group of compounds with similar actions on the body.

It seemed logical to my acquaintence that her body could tell the difference between the estrogen that it made and estrogens that she introduced. "I can tell the difference between real sugar and Sweet-n-Low," she said. One is natural insofar as it is made by plants (sucrose) and the other is made in a lab.

And I'm sure she's right. She can tell which one she thinks tastes better. But to decide what foods are healthiest based on personal preferences regarding taste is an example of the "ick reaction" fallacy, the idea that something must be bad just because of gut reactions. If that were true, and gut reactions to foods based on taste were an indicator of nutritional quality, we'd all eat nothing but cake and ice cream. I recall not liking beets as a child. I still don't like beets; the very idea of eating beets is almost gag-worthy. Beets must be terrible for me! The true believers in natural foodstuffs are going to stand up and tell me something about how I've been brainwashed against healthy food and that the food industry is putting mind control chemicals in my orange juice or something. Moving right along.

Human beings have a wide variety of sensory data that they can use to evaluate their environments. We use vision, smell, and taste to determine what is and isn't objectionable to introduce into our bodies. All of this information is an aggregate of signals from numerous electrochemical receptors, filtered through our brains and interpreted based on existing information, and is remarkably imperfect. Antifreeze is sweet and delicious but highly toxic to the kidneys. Your feelings about a particular food or substance are not necessarily predictive regarding how good (or bad) it is for you.

Here's the clincher. Your individual cells have no eyes, ears, or taste buds. How do they interpret environmental information? It's time for a review of biology.

Every cell in the human body has a number of surface receptors, protein structures stuck in the cell's membrane. These surface receptors are the eyes and ears of the cell; when appropriate substances float by in the fluid environment of the body, a chemical reaction occurs between the substance and the cell receptor. The cell interprets the binding of a substance to its receptor as a message, much the way sticking your car's key in the ignition and turning it is a signal to your car to start the engine. And these receptors are fairly specific, too. Much like you can't use the keys to your 88' Oldsmobile to start the BMW your neighbor carelessly parked in front of your house, cell receptors won't bind compounds totally at random. They have to be properly shaped, in a chemical sense--they have to fit.

Suppose you own that BMW and you put the keys on a really tacky keychain. Will the key still start the car? Of course, you're thinking, the keychain isn't part of the mechanical workings of the ignition. It's totally superfluous. Your car has no idea that you have such bad taste, and it operates just fine even though there's a pink plastic Elvis hanging on the side of your steering column.

And so it is with cell receptors. All cell receptors care about is whether or not the key fits properly, which means that the only thing important for cellular response is the chemical structure of a compound, not whether it was synthesized by a plant or a chemist. Your cell's "senses" are totally reliant on the ability of a compound to form chemical bonds with the cell's receptors. There is simply no way for them to tell the difference in origin between two compounds as long as their chemical structures are totally identical. "Natural" vitamin E is no different from vitamin E made in a lab as long as they're both alpha-tocopherol.

If you've been paying attention, I did note earlier that estradiol and ethinyl estradiol are not chemically identical. They have slightly different structures. How do you reconcile this issue? If they're not exactly the same, how can I tell my friend that they are?

The tacky pink Elvis is part of the structure of my hypothetical keychain, but the car only cares about the key. Pharmaceutical chemists can modify compounds to alter other properties of a drug while retaining the important shapes--the key--that are required to activate cell receptors. Estradiol will have almost no effect if you swallow it in tablet form, because the liver will rapidly break it down into inactive compounds, and the liver is the first stop for any orally ingested drug product. But by modifying estradiol into ethinylestradiol (EE), the compound will survive the trip from the stomach and intestines to the bloodstream and be able to have the same effect that estradiol made in the sex organs would have.

I came up with three different car analogies regarding the liver's rapid metabolism of estradiol, but I'll spare you my prose. And in case you're curious, it is possible to take estradiol orally and have it be effective, but the dose must be considerably larger. Your typical oral contraceptive has 0.035 to 0.05 milligrams of EE, whereas oral estradiol used for the treatment of menopausal symptoms is dosed at 0.5 to 2 mg. These doses aren't necessarily equivalent in terms of their effect, but the point is that EE is a lot more convenient for oral administration in women who are taking low doses of estrogens to prevent pregnancy.

The whole natural versus artificial dichotomy is a ruse; it's a marketing ploy, when we're talking about interactions at the molecular level. You might be able to taste the difference between organic food and non-organic food ("inorganic food" would be something else entirely), but that's only because your higher brain is able to interpret the hundreds of chemical signals recieved by your taste buds and shuttled into the central nervous system. Your opinions about subjective information like taste are colored by expectations, prior experiences, and other emotional data that individual human cells lack. Drug-cell interactions consist of comparatively fewer elements without any cognitive components, only a set of cell receptors that can or cannot be activated by a substance floating around in the bloodstream. Those chemicals are a bunch of keys, floating idly through the body without intention or purpose; all that matters is their coincidental ability to fit into a cell's preset locks.

Tuesday, November 20, 2007

Thanksgiving Hiatus

N.B. is on vacation until the end of the week, taking the typical student opportunity to go home for the holidays, eat free home-cooked food, and catch up with the relatives. He may still respond to emails, but regular blog posts are extremely unlikely this week.

In the meantime, chew on this. It may not be new news, but some people still don't get it.

Saturday, November 17, 2007

My Drug Can Beat Up Your Drug

Abel Pharmboy's post about GSK intimidating doctors makes a recent development all the more darkly humorous.

Apparently, Takeda Pharmaceuticals, the company that makes Actos, is going to go on an advertising spree informing patients how safe it is. More precisely, they're making a point to tell you that, according to at least one study, it doesn't increase the risk of heart attacks or strokes. You know, in all fairness, the black box warning doesn't say anything about heart attacks or strokes--strictly speaking, it's about congestive heart failure, in which the heart is unable to pump sufficient blood to keep up with the needs of the body. And while it's true that Avandia and Actos have different effects on patient lipids, with Actos having a more favorable effect on HDL and triglycerides, the mechanism by which thiazolidinediones (the class of drugs to which Avandia and Actos both belong) increase the risk of heart failure is more likely related to the fact that they cause fluid retention and edema--which has nothing to do with lipid levels.

And even if Takeda did dig up a study saying that the overall risk of mortality for patients on Actos was better, turning it into a direct-to-consumer full-page newspaper ad is just crass. I expect this kind of mudslinging in politics, but in medicine?

Thursday, November 15, 2007

Just Ask Your Pharmacist?

The notion of behind-the-counter drugs that could be sold without a prescription but only by directly consulting with a pharmacist has been tossed around quite a bit by the FDA lately. It's an interesting and somewhat controversial proposition, and apparently the FDA isn't "ready to make any kind of decision."

The AMA is openly opposed to the plan, saying that pharmacists will not necessarily have the required information to do what amounts to prescribing medication. And, in certain contexts, they're right.

One thing that puzzles me is which drugs, exactly, are being proposed to be made "behind-the-counter" (or BTC for short). Some suggestions from the Forbes article include varenicline, Pfizer's new blockbuster smoking cessation drug, the antiviral drug oseltamivir, and cholesterol-lowering statins.

What the hell are they thinking?

There's already a precedent for BTC drugs; pseudoephedrine. America's favorite cure-all for cold symptoms has been behind the counter for some time now to combat methamphetamine production. Many pharmacists have used this as an opportunity to provide additional counseling to patients wishing to purchase pseudoephedrine products, making sure that there are no reasons the patient should avoid PSE or that another product might not suit the patient better. I've discouraged many patients from purchasing PSE in favor of other treatments for cold symptoms in cases when PSE would've been unhelpful, an opportunity I might not have had if PSE were still on the pharmacy floor. And Plan B is essentially a BTC drug, too.

Varenicline makes a little bit of sense, but giving community pharmacists the power to dispense antibiotics or antivirals without a prescription would be a nightmare. Patients would be rushing the counter at all hours, ignorant of the growing problem of antibiotic resistance and demanding amoxicillin every time they sneezed. Pharmacists would be ridiculously overloaded and unable to handle the demand. What's more, most pharmacists only have minimal training in diagnosis and are unable to order lab tests. It isn't our job to diagnose illnesses; it's our job to design, review, and optimize drug therapy. The AMA is right when they say pharmacists shouldn't be throwing around statins any more than statins should be over-the-counter (which has been suggested). Who's going to make sure patients taking statins get regular liver function tests if they can just walk into the drugstore and buy a box of Lipitor on a whim?

I don't object to the idea of BTC drugs, but if the NCPA is going to push for BTC, it needs to have a very clear idea of what it wants to accomplish. Many drugs would be inappropriate for pharmacists to dispense without proper communication between the dispensing pharmacist and the patient's primary care physician. This basically rules out any drug that is taken long-term for chronic conditions. No meds for diabetes, high blood pressure, hypothyroidism, osteoporosis, asthma...the list could go on.

So what could a pharmacist conceivably dispense as a BTC? We're basically looking at short-term therapies. Painkillers? Absolutely not; your corner drugstore would be full of drug seekers from dawn to dusk. Non-narcotic migraine medications like Imitrex could be okay. Oral contraceptives could be a good idea. Anti-nausea drugs like promethazine would be reasonable, but treating symptoms like nausea without investigating their cause is potentially dangerous. But all of these drugs have side-effects, interactions, and contraindications. Pharmacists would have to be very careful to conduct thorough patient evaluations to prevent irrational overprescribing of drugs--which is already a problem with patients who see multiple doctors. Imagine having to factor in multiple pharmacists. Most pharmacists are already sufficiently troubled by patients who won't use the same pharmacy for every fill. And would Corner Drugstore really give pharmacists the time and staff that they'd require to conduct the patient evaluations that they would need to dispense these medications responsibly?

The jury is still out.

Wednesday, November 14, 2007

A Response to "Anonymous"

An anonymous poster commented on my entry about CAM and medical education, which I posted to give a little perspective on my experiences with CAM "infiltrating" schools of medicine--of course, mine is a school of pharmacy, but pharmacy is medicine, and it's my opinion that pharmacists have an ethical duty to uphold the use of scientific medicine. As I started to reply to Anonymous, I found myself writing quite a bit, and it seemed the most reasonable thing to do was to turn the comment into an entry. So, Anonymous, here's my take on what you said:

I focused on homeopathy in this post because it was the specific subject of discussion in the lecture I attended this week for one of my courses, and I wanted to address the way my university discussed homeopathy and "alternative medicine" in general.

In any case, I am not so hasty or ignorant as to "condemn CAM based solely on one modality." I am very familiar with naturopathy, chiropractic, acupuncture, ayurveda, and TCM. My girlfriend, for what it's worth, spent a summer in Mumbai studying the integration of ayurvedic medicine into Indian hospitals and analyzing the cultural impact of ayurvedic medicine on the Indian population.

You are correct in the sense that some CAM modalities may have plausible biological mechanisms of action. Naturopathy in particular; herbal medicine is not necessarily a placebo, and many "herbal medicines" contain biologically active compounds. The question, as you so astutely pointed out, is the level of evidence supporting the use of a particular modality.

The problem, then, is the fact that these methods are not abandoned when they are found to be ineffective. Acupuncture may relieve pain, but it will do nothing for immunological disorders. Chiropractic might be useful for lower back pain in some patients, but it certainly isn't going to do anything for diabetes, allergies, or inner-ear infections. You could drink willow bark tea for pain and fever, but you're also ingesting a bunch of other biologically active compounds that do nothing for your specific problem; it's safer and more focused to take aspirin.

There is no "alternative medicine." There is medicine that works and medicine that doesn't. Many experimental procedures are adopted into common practice once they are proven to be effective. And many "mainstream" therapies that turn out to be poor or ineffective options are discarded. Notice how Exubera, the inhaled insulin heavily marketed by Pfizer, was discontinued after only a two-year run? It was a novel idea, but a crappy drug. Dosing it was a pain in the ass, the inhaler was bulky and annoying, and it wasn't any better than using an insulin pen. The recent removal of infant cough and cold drops from pharmacy shelves was spurred by a lack of evidence for their safety and efficacy as well as concerns about overdoses. Many practitioners are arguing against the use of propoxyphene because it's a lousy painkiller and can have toxic side-effects in the elderly. Even aspirin is no longer recommended by many health care practitioners for analgesia; the much safer acetaminophen is recommended instead. When was the last time naturopaths said "quit using glucosamine, studies are inconclusive about its efficacy" or chiropractors suggested people should stop getting adjustments because they weren't doing any good?

I am inclined to dismiss any form of treatment not validated by scientific evidence. This doesn't stop me from learning about CAM modalities, especially herbal medicine, so that I can inform my patients about potential drug interactions or side-effects. It would be a terrible mistake for me to be ignorant of CAM. That doesn't mean I think it's generally useful. I don't recommend black cohosh or phytoestrogens for menopause. I don't suggest that my depressed patients start taking St. John's wort, even if it is potentially efficacious, because of the huge drug interaction profile (and if I ever see anyone purchasing it I always ask if their physician is aware that they take it and get a full list of their medications). I don't recommend men take saw palmetto or suggest cranberry tablets for urinary tract infections. I don't do any of these things because I don't have sufficient evidence that they are good treatments, even if patients swear by them. How many patients know whether or not saw palmetto is shrinking their prostate, anyway?

You ask me if I've ever dispensed a prescription drug that was not "vetted by clinical trials." Of course I have, but I'm also not a pharmacist yet, and I don't have the power to refuse to dispense prescriptions because they're being dispensed for non-evidence-based indications. But that doesn't mean I don't see it happening. I cringe when I see quinine dispensed for leg cramps (which you'll note the FDA doesn't want you doing either). I don't recommend guaifenesin unless patients are absolutely desperate to take something for chest congestion because increasing water intake works just as well, and the long-acting guaifenesin-only products are incredibly costly. I don't care whether medicine is "alternative" or "western" because the distinction is meaningless. If it works, science will be able to demonstrate it works, and I'll support its use. If it were empirically demonstrated that standing on your head cured diabetes, I would build a jungle gym in my store's parking lot.

If science doesn't support use of a treatment modality, why should I support it? Because it makes people "feel" better? If it doesn't do anything to actually help the patient's condition, it does them no good, especially in serious conditions. And the "worried well," the people you're talking about that are involved in "wellness programs," the people for whom "CAM is most useful," aren't sick. What is a "wellness program," anyway? "You're already healthy, here's how you stay that way." And the answer to "how you stay that way" is "fork over lots of money for supplements, adjustments, and lab tests." That's a huge part of my objection. CAM practitioners are essentially making money off all their money off of "health conscientious" hypochondriacs and desperate people who'll try anything (i.e., cancer patients). People downing Airborne, zinc, and vitamin C for colds amaze me; a cold lasts maybe a week at most. You're willing to go to that much effort because it might decrease the duration of your cold by what, 24 hours? Maybe? And isn't it wrong--an outright lie--for me to tell my patients that they should try remedies that aren't supported by evidence just to placate them?

And I haven't even addressed the fact that many CAM practitioners hold and promote outright dangerous "health beliefs," such as the typical anti-vaccination rhetoric. Others support or "treat" fictitious diseases such as Morgellon's and "multiple chemical sensitivity." Physicians aren't necessarily honest, but no physician I've ever known has had to invent diseases to get more business. There are plenty of real diseases plaguing humankind to keep us occupied for a very long time.

What place does CAM serve? "Complimentary" medicine should do something above and beyond "the other medicine" in order to be worthwhile. If complimentary medicine can't stand on its own, what good is it unless it significantly amplifies the power of traditional medicine? During the Second World War, probenecid was used to extend the supply of penicillin to treat infections--THAT is complimentary medicine. Acupuncture may reduce required painkiller doses for surgery, but is that clinically significant? Does it really affect the patient in the long term, and is it cost-effective? And as I've already said, there's no such thing as "alternative" medicine. It works, or it doesn't. End of story.

Pharmacists are scientists, and even if medicine isn't a perfect science, it's foolish to abandon science for wishful thinking or to appease patient delusions. It is both logically and ethically inconsistent for me to endorse the use of CAM.

Be Pharmsavvy

With five exams and a written essay due this week, yours truly N.B. is quite the busy student. But like almost all students, I have been working for years to perfect procrastination, making it more of a science than an art. As such, I have more than enough time to keep up with the blog world--sorta. For your daily update, here's a bit of pharmaceutical trivia that will make you look smarter. Or smart-assier. But if you get as much pleasure out of nitpicking and semantics as I do, you're in for a treat.

The word "pill" is commonly used to refer to any oral dosage form that is swallowed, be it a tablet or capsule. "I need my pills," my patients often say, or, my personal favorite, "I need my pill," which, even without looking at the patient or hearing a voice, means nine times out of ten that the patient in question is female and looking for her oral contraceptive to be refilled.

But pills are an archaic dosage form that is no longer used, made by pharmacists rolling measured amounts of active ingredient into balls of beeswax or other materials. Nowadays, oral dosage forms are typically pre-made in large factories instead of being compounded on-site at the pharmacy. Most outpatient pharmacies, except those that specialize in compounding, do not make their own tablets (which requires a lot of machinery) or capsules (which is considerably easier).

So you don't take "pills." Nobody has taken pills for years, because nobody dispenses pills anymore as they aren't manufactured en masse by the industry.

Maybe this knowledge will propel you to victory on some game show someday. Then again, maybe not.

Tuesday, November 13, 2007

Your Sinister Public Broadcasting Network

I just got a moment to look at the Discovery Institute's take on the PBS special set to air tonight regarding intelligent design, and I couldn't help but burst out laughing:

The trailer for the program shows that PBS has turned to the usual suspects to advance their agenda.

The usual suspects. Their agenda.

I wonder what Mr. Rogers, Elmo, and the Teletubbies have to say about PBS's leftist atheist agenda?

CAM and Medical Education: Close, But This is a No-smoking Section

Orac of Respectful Insolence and Panda Bear, MD have had some great things to say about so-called "complimentary and alternative medicine" lately, notably some discussion about the infiltration of woo at major universities, including Ohio State.

I have a cousin that graduated from their medical school. I cringe at the idea that he might've been infected with woo, or, perhaps just as bad, the idea that we should be absolutely tolerant of woo. On the other hand, the last time he and I talked shop, there was no indication that he was abandoning his promising career in anaesthesiology to become a swami or move out to Andrew Weil's place in Arizona, so I can let loose a sigh of relief for now.

Woo hasn't infiltrated my university, as far as I can tell--not yet, anyway. But if a recent lecture is any indication, the university isn't taking a hard stance against it. I can see why not. Such a maneuver would arguably be politically loaded, and my university advertises itself as a school for the liberal arts. Oh well. But as a current student receiving a medical education, I think I have a unique insight into what's going on in academics today. Call it "insider information," if you will.

At first, I was kind of worried. The professor started by explaining the regulatory process for homeopathic products in the U.S. Standard stuff, really. But then she got into talking about the Law of Similars and the Law of Infinitesmial Dose. Granted, she was prefacing her statements with "homeopaths believe" and "according to homeopathy," but the way she was talking left me wondering where she might be going with this lecture. Was she going to conclude that homeopathy was an equally valid way of looking at medicine, even if, as she admitted to us, she had trouble understanding how it was supposed to work? I scanned the audience for reactions from my peers. Inscrutible. How many of them knew anything about homeopathy and sCAM before this class? Considering that I found QuackWatch as an indirect result of an assignment about a year or so ago, I found it hard to believe that they could all be totally ignorant of the subject.

It was at this point that the professor noted that she wasn't entirely sure how she should give this lecture, and that was why she had prepared a video clip for us to watch instead. "Homeopathy," concluded the program clip, "is impossible." The clip got quite a few laughs, and when we took a short break afterward, the room was abuzz with student chatter. "I never knew homeopathy was infinitely diluted!" "Oh, so that's what homeopathy is?" "I knew a woman who..."

Honestly, it was a breath of fresh air.

The professor noted that she "had trouble" buying into homeopathy because she was a scientist. As a fan of evidence-based medicine, she couldn't recommend it to other people, nor did she think it was terribly useful. But she did note that a lot of people swear by it, and she joked that it was very popular with new parents--at that point, you're basically treating mom and dad instead of the kid. She made it very clear, in a roundabout, placating manner, that she didn't think homeopathy was useful medicine, but she didn't come down hard on it as a scourge.

I can see why this might be the approach taken by major universities. As I mentioned earlier, it's all about politics. I think it's fair to call it "appeasement," hearkening back to the days of the Communism and the Cold War, although that's potentially an overdramatic analogy. Some professors are afraid to step on the toes of their students, at least a few of whom might favor alternative medicine, or at least bear it no ill will. But I'm not sure that's the only motivation; I think that by strongly denouncing homeopathy, professors of medicine and science will look like rabid zealots, and students will slam their ears shut like Creationists do when their profs start discussing evolution. By presenting the case against sCAM too vociferously, we may alienate supporters by looking like fanatics. Instead, the strategy employed (at least, by this professor at my university) seems to be more along the lines of "here's some information, here's a video clip, make up your own minds." Which is good. The idea that ritualistic indoctrination against sCAM would be counter to the ideals of the critical thinking process.

It would also appear to validate the conspiracy theories of altmedders, but they aren't letting go of those anytime soon anyway.

So I understand the approach. But I still don't like the "appeasement." Medical professionals giving lip-service to sCAM as "having some potential value--making people feel better" when it "isn't likely to cause harm" is inconsistent, because I've also been told (although by another professor) that you should never reinforce patient delusions. And isn't it unethical--a lie by omission--to tell a patient, "it's okay, go ahead and try it, it might help and isn't likely to hurt?"

According to an article I dug up, 50% of medical interns learned about the use of placebos from other physicians. They are influenced by mentors and by writings by mentors, not necessarily taught to use placebos in an academic setting. It is obviously necessary to use placebos to conduct drug trials. But placebo usage in clinical settings is not ethical. Even the "evil" and "fascist" AMA says so. Imagine that, the AMA standing up for patients! How would you like your crow, CAM devotees?

It can't be all about money, at least, not from the end of academic institutions. I think some of them are legitimately afraid of alienating people by coming down hard on sCAM. And others fear that being too enthusiastically anti-sCAM will make them look like fascists, fanatics, or both. Herein lies the dilemma. If education is the primary weapon against sCAM, what are we going to do?

Monday, November 12, 2007

I Really Wish...

I could post something that was good news, because right now I'm breaking into the blogosphere with a crash of pessimistic thunder and accompanied by an armada of dark storm clouds.

Unfortunately, I hope you brought your umbrella, because a federal judge just suspended a state law requiring pharmacists to dispense emergency contraception, otherwise known as "Plan B." According to the article, the law unconstitutionally violates pharmacist's freedom of religion:

The rules appear to force pharmacists to choose between their own religious beliefs and their livelihood, Judge Ronald B. Leighton of the U.S. District Court in Tacoma wrote Thursday.

Some pharmacists believe the emergency contraceptive pills, also called "morning-after pills," are tantamount to abortion because they can in some cases prevent implantation of a fertilized egg.

"Whether or not Plan B ... terminates a pregnancy, to those who believe that life begins at conception, the drug is designed to terminate a life," the judge wrote in a 27-page order granting a preliminary injunction.

As a little background, Plan B consists of a package containing two 0.75 mg tablets of levonorgestrel, a form of progesterone. One tablet is intended to be taken as soon as possible, with the second tablet following 12 hours later. The sooner the first dose is taken, the better; this is a drug where time is crucial. Because Plan B is now available "over the counter," it may be true that if one pharmacist refuses to dispense the drug that the patient can simply go to another pharmacy. But what kind of option is that? Every minute counts. And isn't it possible that every pharmacist within reasonable distance of your home might refuse you EC just because they don't think you should be permitted to have it?

It doesn't help that few people actually understand the science behind Plan B, even pharmacists. 25% of pharmacists surveyed in North Carolina thought Plan B was an abortion pill like mifepristone (RU-486), which will actually terminate an early-term pregnancy. 5% who knew that it wasn't RU-486 still thought it could somehow directly induce an abortion. They've apparently forgotten their physiology; part of the way that the body maintains pregnancy is jacking up serum progestins to keep the endometrium from sloughing off and dumping out an implanted fetus with the next menstrual load. No wonder they're opposed to it; they have no idea how it works! In fact, RU-486 works because it's an synthetic anti-progestin steroid. And it's commonly cited that Plan B works by preventing implantation, which is only partly true; like other oral contraceptives, Plan B also alters cervical mucus and the action of the fallopian tubes. It may even prevent ovulation entirely, depending on where the woman taking it is in her cycle! It may, in many cases, prevent union of sperm and egg altogether. Even if it didn't, refusal to dispense EC but dispensing other oral contraception is logically inconsistent. They have identical mechanisms of action.

Think about it this way. Suppose you were seriously injured and losing large amounts of blood. You desperately need a blood transfusion. The attending physician at the ED appraises your condition and shakes his head. "This patient is bleeding to death," he says to his colleague, "but there's nothing we can do. It's for his own good that we not save his life. I won't be responsible for condemning his immortal soul."

Sound impossible? Maybe. But a woman recently died during delivery of twin babies for refusing a blood transfusion. She was a Jehova's Witness, and her religious beliefs prevented her from recieving blood transfusions. It is common legal and ethical precedent that physicians cannot treat patients without their consent. And a doctor who refused to treat patients on the basis of his or her religious beliefs could potentially be sued for malpractice. Why can't the same be done for a pharmacist? Pharmacists have been sued over this issue in the past; why in the world would a court overturn that ruling now?

Perhaps the issue is one of urgency. Any layman can tell you that severe hemorrhage is potentially fatal, and very quickly so. But what about symptomatic iron-deficiency anemias? Treatment protocol for patients experiencing significant shortness of breath or other potentially serious problems includes an infusion of red cells. Can you imagine a doctor telling a patient, "it's okay, just take iron supplements for the next month, eventually you'll get better without a blood transfusion?" It might potentially be true, but does that mean it's good medicine? It's vastly subpar care with no medical basis or scientific evidence to back it.

The article mentions that most people "can get Plan B without a pharmacist," but as I understand the matter, that's an issue of state law as well. Where I work, a patient must present an ID to purchase Plan B, and all sales must ultimately go through the pharmacist. If the pharmacist refuses to sell Plan B and finds out that a technician has violated this decision, the technician could very easily be fired. How many technicians will risk their jobs like this?

In summation, I really have to agree with one of the activists quoted by the article:

"I think this is another step on the assault on women's rights to control our own bodies," said Helen Gilbert, an activist with the group Radical Women. "If [pharmacists'] beliefs are in conflict with doing this job, then they should do a different job." [Emphasis mine.]

Absolutely. To quote a pharmacist I used to work with, refusing to dispense oral contraceptives or emergency contraception is like a Christian Scientist getting a medical degree and then refusing to treat anyone except with prayer. Why would you take the job if you find it incompatible with your belief system? You are responsible for certain things as a medical professional. If you don't like them, find another line of work.

Immunoglobulin E are the bane of my existence.

I am convinced that, despite the claims of some, my immune system hates me and wants to see me suffer. I am thankful for all the times that it has worked to fight off infectious pathogens and I would hate to see it go, but this double-edged sword is mercilessly hacking apart my face.

Why can't you just give it up, IgE, and quit being such a bastard all the time, trying to hog the spotlight in the face of more useful immunoglobulins like IgA and especially IgG? Those immunoglobulins are more effective at anti-pathogenic action without being able to destabilize mast cells and dump histamine everywhere like a proverbial allergenic Exxon Valdez. While we're at it, you can tell your eosinophil friends to pack it up and move out. I'm about ready to selectively lyse any cell in my body that even so much as considers transcribing mRNA that encodes for vasoactive amines.

If you'll excuse me, I'm going to declare war on green plants and the feces of microscopic arthropods now.

Corpo-Pharma's Silent Assault on Pharmacist Ethics

I work for a major pharmacy retail outlet, and by and large, they've been good to me. It pays the bills, and I've had the opportunity to work with some amazing pharmacists and technicians who have had a profound impact in shaping the kind of pharmacist I want to be.

Pharmacists have a pretty good reputation with the general public. If opinion polls are any indiciation, the public trusts their pharmacists. Voted second most honest profession in America, in fact. Commercials by all the major chains want to portray pharmacists as reliable, accessible, knowledgeable, and friendly. Many of the pharmacists that I've worked with have been all of these things, and they've given me a model for my future.

This is why nothing makes me hot under the collar like an unethical pharmacist. Or, perhaps, to state things a little more broadly, like unethical pharmacy. You don't really hear about it as often as you hear about the transgressions of other medical professions. Most physicians and surgeons carry malpractice insurance for a reason; they have high-profile positions, and negligence and maleficence are not tolerated. And those paying attention to the practice of quackery are quick to sting any physician who would overpromote services like chelation therapy for autism or DCA for cancer. So when I flip through pharmacy's professional magazines and spot advertisements for unproven therapies, I think I have a right to be disgusted. What respectable pharmacist's publication is going to run ads for homeopathic products? But DrugTopics has done it. So has Drug Store News, and they do it regularly; at the time of my visiting their website, the front page proudly displays an ad for cranberry supplements suggesting pharmacists "tap into the number-one selling herbal product." A magazine aimed at technicians I was looking at the other day actually mentioned Similasan, a line of homeopathic eye and ear drops, as a legitimate therapeutic option for infections that didn't require a doctor's prescription or contribute to the dreaded antibiotic resistance epidemic. Their heart is in the right place, if they're hoping that promoting homeopathy to treat self-limiting infections will cut down on the development of strains like MRSA, but it's an established convention in medicine that use of placebos is unethical because of little things like "patient consent."

The rare pharmacists who run independents these days have no excuse, but we in the chain world are stuck under the oppressive thumb of corporate masters who have no apparent concern for things like "ethics" or "honesty" when "the dollar" is concerned. It's true that Corner Drugstore Inc. is watching out for their patients in the big ways. They've implemented all kinds of safety features to cut down on misfills and mix-ups, because these are the kinds of things that they imagine might actually hurt someone.

(Read: These are the kinds of things that Corner Drugstore, Inc. might be held personally accountable for.)

No one is going to hold Corner Drugstore accountable if the latest "wonder diet drug" turns out to be unsafe or a child dies because the drugstore sold the parents homepathic remedies when the child needed real medicine. Or at least, I can't find any evidence that Corner Drugstore has ever been held accountable.

I am approached by patients with great frequency who are trying to find HeadOn, zinc, selenium, vitamins for every body system imaginable, untested probiotics, Emergen-C, you name it. Our shelves are stocked with homeopathic "anti-snore" tablets and throat spray somewhere underneath the Breathe-Right strips, leg cramp medicine supposedly containing quinine that would be lucky to contain one molecule of the stuff, and at least one "stress tonic" herbal formulation promoted for sleep that costs at least ten times as much as generic diphenhydramine tablets. "Which of these will help me with my cold?" a man asked me one day, dropping a plethora of boxes on my pharmacy counter. Two boxes of zinc lozenges, different brands, accompanied by Airborne and a store generic version of the same. As the Drugmonkey once quipped, I could've told him to eat the box containing the Airborne and he would've gotten the same therapeutic value out of stuffing his mouth with the corrugated paper as he would consuming the contents. Probably. Come to think of which, that fiber would be good for the colon. Maybe eating the box would've been better in the long run.

Here's what bothers me. These patients usually aren't woo-meisters. They're not dedicated worshippers at the altar of altmed. They're confused and lost souls, bewildered by the array of products available on the pharmacy shelves. Maybe they saw an ad on television for the product they're looking at; that's the kind of thing that motivates patient choices about self-medication above all else, pharmacist input included, if my anecdotal experience is worth anything on the matter. And Corner Drugstore Inc. is throwing a huge monkey wrench into the whole "counseling and patient education" pharmacists are supposed to do by having these products on their shelves, because this is the pharmacy, and patients go to the pharmacy to get medicine (or light bulbs, or batteries, or toilet paper) and by God, if it's for sale in the pharmacy right next to the Tylenol, of course it works! Why would the pharmacy sell medicine if it didn't work? This concept is so foreign to patients that most of them tend to give us blank stares. It totally flies in the face of the "you can trust your pharmacist" mantra.

At Corner Drugstore, We're not the ones stocking the shelves. But the average consumer links everything even vaguely medicinal in a drugstore with the pharmacy. It's this tacit endorsement of altmed--cough, "health freedom"--that drives me into a vial-throwing frenzy. Those 40-dram vials are pretty big. If I fill them with expired ibuprofen they make decent projectiles. Duck and cover!

My store's manager asked me once what I liked and didn't like about my work environment. "If you could change one thing about the store, what would it be?" Most of the responses from coworkers were things like "please turn down the awful Muzak." I told my boss that nothing would make me happier than to see our store stop stocking unproven medical or drug products of all varieties, including untested herbals and homeopathic remedies. I don't think I've ever gotten such a strange look in response to something I've said.

The thing is that the pharmacists I work with agree with me. They complain all the time about the "junk" on our pharmacy shelves and get tired of trying to explain to people why we stock "fake medicine." Here's why we stock fake medicine: Because people keep buying it, and Corner Drugstore doesn't care how that reflects on pharmacist ethics. And Corner Drugstore's biggest committment is ultimately to making mone--er, I mean, upholding health freedom and patient choice.

Pharmacists are supposed to be scientists. And most of the pharmacists I've known have been very good when it comes to their ethical and scientific integrity. I think it might be worse when pharmacists turn to woo than when physicians do it, somehow, especially things like homeopathy and herbal products; they're supposed to be drug experts! How could anyone with four to six years of chemistry, biology, biochemistry, pharmacology, and physiology be sucked into promoting quackery? The answer, of course, is that most of them aren't. But I have worked with pharmacists who felt it was easier to say "well, go ahead and try it" than try to educate patients about altmed. Part of this is because Corner Drugstore pharmacists, no matter what anyone tells you (or what you're told in pharmacy school) do not generally have time to do serious patient education. When a store is busy, your pharmacist barely has time to go to the bathroom, much less explain the fact that dietary supplements are on the shelves because of legal-political lobbying and not stellar drug design and research. Patient education is a service that gets thrown by the wayside in busy stores where all that matters is prescription volume, sales statistics, and the results of customer surveys. Is this really an environment conducive to education or science?

Pharmacists have the opportunity to be the cornerstone of anti-woo among outpatients. We have to convince Corner Drugstore to let them.

Friday, November 9, 2007

Natural Selection

Some high school students have apparently been exposed to methicillin-resistant Staphylococcus aureus. Commonly abbreviated to MSRA, methicillin-resistant Staphylococcus aureus is one of many threatening infectious disease strains that has developed as a result of overuse of antibiotics.

The idea of bacteria that can't be treated with common antibiotics is kind of scary. It's not that MRSA is totally untreatable; there are a few drugs that are still effective, but the danger is that eventually bacteria will develop resistance to them, too. The media is naturally being somewhat alarmist, but in this particular case I'm more inclined to fault them for not bringing up why MRSA is on the rise.

We're entering cold season, and every year people call their doctor or drop into the office and beg for relief. They expect a prescription. Why else would they go to the doctor? The net result is that as many as 50% of outpatient antibiotic prescriptions are totally unnecessary. Some are dispensed to treat infections that are ultimately viral. Others are prescribed for patients who would get better on their own at almost the same rate. Antibiotics are completely worthless against the common cold, and patients pressuring doctors to "just give me a prescription" are contributing to the development of bacterial strains that are getting progressively harder to treat.

A lot of pharmacists I've worked with view any patient on opiates for chronic pain or anti-anxiety medications as potential drug addicts and express frustration with physicians for being too free with their prescription pads. I think that their feelings are misguided. Even if a patient is a drug-seeker, addicts are primarily hurting themselves. Overuse of antibiotics is a problem for our whole species. I'd much rather see doctors throwing fistfuls of Vicodin at patients than giving everyone who comes into their office a Z-Pak just to shut them up.

When Pharmacists Fail to Counsel

The birth control patch is a hormonal method that slowly releases female hormones into the body through the skin. Normally, it should be applied to a clean, dry, hair-free area of the body.

Apparently, at least a few patients, in a spectacular failure to read directions, decided that it should be applied directly to "the area."

Note well: The birth control patch does not do double duty as a barrier method of contraception.

Marketing and Medicine: Part Two

Last entry, I mentioned that there are at least 14 different formulations produced with the Tylenol brand name to help treat cough, cold, and flu symptoms. Here's a piece of valuable information. There aren't anywhere near 14 different drug ingredients on the market for cough, cold, and flu.

Any pharmacist can tell you that all these products are just rehashings and reformulations of the same five or six different drugs in different combinations with fancy new labels. And Tylenol isn't the only corporation using this strategy; they all are. Pfizer has half a dozen different Sudafed products to capitalize on the popularity of the brand. Wyeth's Robitussin is the same deal.

There are five big drug classes used to treat cold and flu symptoms: Pain relievers/fever reducers, antihistamines, decongestants, cough suppressants, and expectorants. Most of the multi-symptom cold products contain Tylenol, otherwise known as acetaminophen, as a pain-reliever and fever reducer. You'll see a lot more combination products with acetaminophen than you will other pain relievers like ibuprofen because acetaminophen has fewer gastrointestinal side-effects and isn't as likely to interact with other medications. And no matter how many different "cough" products you see marketed, there are only two FDA-approved "cough" ingredients commonly available OTC, those being dextromethorphan and guaifenesin. Dextromethorphan is a cough suppressant available in a wide variety of products, commonly those tagged with "DM," like Mucinex-DM, but you'll rarely find it by itself. Guaifenesin is an expectorant, which thins secretions in the lungs and chest to make them easier to cough up.

The attentive reader (or those living outside the U.S.) will note that I didn't mention codeine, because getting codeine cough syrup without a prescription in the States is practically impossible because of how much paperwork and hassle is involved in selling it. It's more abusable, honestly doesn't work any better than dextromethorphan, and a huge pain in the ass for both pharmacists and the chains they work for.

So no matter how many cough medicines are on the shelves, they all contain more or less the same thing in different boxes. And it doesn't matter what the box looks like; all that matters are the active ingredients listed on the back.

My personal favorite "misleading" branding/packaging in the Tylenol line is either Tylenol Sore Throat liquid or Tylenol Severe Allergy. The sore throat liquid is a great source of amusement for me because Tylenol itself is an excellent treatment for a sore throat; there's no need to add anything else to it. But many people think that medication for a sore throat or to stop a cough needs to be a liquid so that it can coat the throat. This is totally false. Liquids might have a soothing effect on the throat, such as hot tea, but as long as the acetaminophen dosage is the same, it doesn't matter whether you drink it or swallow a tablet. It's all going into your bloodstream before it does any real work, although the liquid might theoretically work slightly faster because liquids are absorbed more quickly. That has more to do with what goes on in your intestinal tract than anything involving your throat.

The "severe allergy" product amuses me because the only ingredient in the product that will do anything to reverse an allergic reaction is diphenhydramine, otherwise known as Benadryl. If you're having a truly "severe" allergic reaction, you need an EpiPen or steroids like prednisone. Benadryl is just not going to cut it.

Combination products with three or four different ingredients are a "shotgun" approach to symptoms. True, you're probably covering all the potential problems, but you're also probably taking at least one medication that you don't need. Tylenol PM is my least favorite product on the pharmacy shelf; it's a combination of acetaminophen and diphenhydramine. Acetaminophen, flat-out, does not cause drowsiness. It plays absolutely no role in helping you sleep. It's the diphenhydramine that knocks many people out. Again with the Benadryl. I always tell people looking for the Tylenol PM to get a box of generic diphenhydramine instead. It's going to have the exact same effect, it's cheaper, and you're not taking unnecessary acetaminophen, which can be toxic to the liver. True, most people aren't going to even approach a toxic dose of acetaminophen by taking Tylenol PM, but if you start combining cold products without reading the labels it's pretty easy to approach the 4 grams/day limit. The manufacturers know this, too, which is why a lot of packaging carries text that says "acetaminophen warning" now.

So be pharmsavvy and ignore the front of the box. Flip it around, check the ingredients, and ask your pharmacist for help selecting individual products for specific symptoms instead of assuming that just because something says "cold and flu" that it's the magic remedy you're looking for.

Thursday, November 8, 2007

Marketing and Medicine: Part One

Brand recognition is a huge part of the American shopping experience. We frequently buy things based solely on whose name is on the package. A study I read a while back suggested that children ages 3 to 5 reported food in McDonald's wrappers tasted better, even if the food was identical to food in plain wrappers or the food--carrot sticks, for example--wasn't served at McDonald's.

This creates a huge problem when it comes to self-medication.

The aisles of your typical community corpo-pharmcy are well-stocked with a plethora of available options. Colorful boxes with household names like Tylenol, Advil, Sudafed, Mucinex and Robitussin stand out amongst less well-marketed remedies like Chlor-Trimeton. The average American consumer cannot be expected to remember each and every ingredient that goes into typical OTC products, so they rely on friendly packaging to tell them what to buy. The Tylenol brand alone has a dizzying number of spin-offs: Tylenol Allergy, Tylenol Sinus Congestion and Pain, Tylenol Chest Congestion, Tylenol Cold Multi-symptom, Tylenol PM, Tylenol Sore Throat Daytime, Tylenol Sore Throat Nighttime, Tylenol Cough and Sore Throat Daytime...according to the Tylenol website, the Tylenol corporation manufacturs 14 products to treat cough, cold and flu symptoms in adults. And that's just a sample.

The problem is that what's on the front of the label has nothing to do with what's in the medication.

I think the best example is Pepto-Bismol. Pepto-Bismol is one of those ubiquitous drugs that some people just love to death. It is often touted as the cure for every possible source of nausea known to man, hangovers, heartburn, diarrhea, intestinal abuse by five-alarm chili, and jock itch. I even managed to find a blogger talking about making Pepto-Bismol ice cream as his ultimate remedy for "the morning after."

In case it weren't obvious, I was joking about the jock itch.

Pepto-Bismol, if you've been living in a cave with no television for the past several decades, is a thick, pink liquid that contains an ingredient called bismuth subsalicylate, or BSS for short. BSS is a pretty interesting drug in that scientists aren't entirely sure how it works for some of its purposes; the stomach-soothing effects are mediated by affecting gastrointestinal mucosal linings, for example, but the heartburn effects are less well-understood. It also comes in a chewable tablet form for those who dislike having to chug the more traditional form of the pink stuff; it's also a whole lot more convenient for travelling, unless you really like carrying an 8-ounce bottle of pink goo.

Then there's Children's Pepto. The packaging for Children's Pepto is very similar to the regular Pepto, though it only comes in chewable tablet form. Children's Pepto doesn't contain BSS at all. In fact, Children's Pepto contains calcium carbonate, which, aside from being a mainstay of blackboards across the globe, is the acid-neutralizing compound found in Tums and Rolaids. It isn't chemically related to BSS at all, and it doesn't have nearly the same versatility; unlike BSS, Children's Pepto isn't going to do anything for diarrhea, for example.

The issue is not that Children's Pepto contains an "inferior" ingredient. The issue is that regular Pepto's BSS is a salicylate, like aspirin. And use of salicylates in children is linked to the development of Reye's syndrome, a life-threatening neurological disorder.

Pepto-Bismol has plenty of warnings on the back telling you not to give it to children--if you read the fine print. But it's an easy mistake for a parent to make, given the fact that brand recognition, not the drug facts on the back label, is what motivates most people to make their OTC purchases in the first place. Children's Tylenol is still Tylenol, but at a lower dose; it's easy to see why someone might assume the same is true for Pepto-Bismol, a drug commonly thought to be totally harmless, and administer it to their child.

So pay absolutely zero attention to what's on the front of a medication label. Turn it around and read the back. Read it closely. Check the active ingredients. And if you're uncertain in the least whether or not a product is right for you, ask your pharmacist. That's what they're for.

Wednesday, November 7, 2007

Irrational Exuberance

Alan Greenspan, former Federal Reserve Chairman, used the phrase "irrational exuberance" to refer to a kind of overenthusiasm for the market during an economic boom; notably, he only used it once, and there was a worldwide plummet in stock prices following that speech, but I think it's an appropriate term to refer to something that I've thought about quite a bit.

I love the drug companies. I really do. We've come a long way in the past 50 years in terms of effective pharmacological treatments for illnesses across a broad spectrum because of dedicated scientists and researchers working to develop the next blockbuster drug. These companies really are doing the public a great service. Just to throw out an example, cholesterol-lowering statin drugs are estimated to have saved 83,000 lives in the last 20 years. Most people nowadays die of heart disease or cancer instead of typhoid and diphtheria, and the death rate due to coronary artery disease in the U.S. has dropped 25% since 1994.

The drug companies are providing a valuable service. And like any other service, we have to pay for it. I don't think that's wrong, really, because pharmaceutical research companies have to make money too. It's not a crime to want to make money, especially if you've invented or discovered something useful, whether it's a rubber O-ring that holds together mechanical parts better than existing joint fasteners or a tiny carbon-based compound that relieves migraines. Of course pharma is "in it for the money." They have to eat, too. If I didn't get paid to do my job, I'd quit. I sincerely doubt you can find anyone who's willing to work for free full-time, no matter what field we're talking about.

What I don't like is when they're being dishonest about it.

I don't mean dishonesty that they're trying to hide. I can't do anything if Lilly or Glaxo or Roche or whoever is committing tax fraud or exploiting weird financial loopholes to widen their profit margins, and while I do care about it, it's outside my area of expertise. I'll leaave that to the lawyers and the accountants to scrutinize. No, what drives me nuts is when pharma is talking about their latest product like it's the greatest invention since the wheel when in fact it's about as useful as most of the gadgets you see on late-night infomercials.

Usually this sort of thing comes up when a company is about to lose their patent on a drug, at which point they attempt to extend the life of their branded drug entity by rolling out products with new release mechanisms (Coreg vs. Coreg CR, for example) or "follow-on" drugs that are actually derivatives of the original drug molecule. The drug Celexa is a great example--Celexa's generic name is "citalopram." It's an antidepressant. Like many drugs, its structure is complex enough that the "mirror image" of that structure is not the same compound. Essentially, at least one set of chemical functional groups is "reversed" in its rotational arrangement in three-dimensional space. This is really kind of complicated, so here's a way better link to explain what I'm takling about:

Someone else can teach you organic chemistry.

Usually, the left-rotating and right-rotating compounds get designated as L (levo, or left) or D (dextro, or right) enantiomers of a substance. Sometimes the letter S is used, for the Latin word for left ("sinister").

Anyway, Celexa as a drug is a 50/50 mixture of both S-citalopram and R-citalopram. Some pharmaceutical chemists playing around in the lab figured out that the S-citalopram is the part that's doing the real work, so some time later they decided to develop a way to just synthesize the pure S-form (which is harder, incidentally) and marketed the new drug as "escitalopram." Say it aloud. Cute name, no?

Escitalopram is available in dosages that are half of what Celexa comes in--Celexa tablets come 10, 20, and 40 mg. Escitalopram tablets are 5, 10, and 20 mg. The theory is that by getting rid of that R-form and dosing the patient with only the pure S-form you end up with fewer side-effects or better efficacy. Sometimes that's true. Sometimes it isn't.

Escitalopram, for the curious, is the popular antidepressant Lexapro. By purifying the S-form from what chemists call the "racemic mixture" (the 50/50 mix of both forms), Forest Pharmaceuticals gets to call what they've cooked up a "new drug" and has an exclusive patent on their creation for about the next 20 years. Joy! Studies do suggest that Lexapro works a little better than Celexa, and that it's slightly better tolerated, but it's also pricier because it's currently brand-name-only: $80.31 for 30 tablets of the 10 mg strength vs $39.99 for the roughly equivalent generic citalopram 20 mg tablets. It might be worth the difference. It might not. The drug companies really want you to think it is, and they tell doctors that Lexapro is way, way better than Celexa, because it's about twice as expensive. They tell pharmacists that it's better, too, and occasionally bother to produce the graphs that prove it. And pharma is really big on phrases like "not equivalent" when they're comparing their new drugs or dosage forms to old drugs or dosage forms. They insist very strongly that the drugs are not the same, and woe to any pharmacist who dares suggest the older drug is just as good as the new one. Some patients will ultimately try both and like one or the other better. That's cool for them.

I don't appreciate pharma sending a rep into our store to talk about how Lexapro is so much better than generic citalopram that any effort to inform patients that yes, there are generic antidepressants that are cheaper (if you would like to save money) is tantamount to blasphemy. How dare you compare their superior product to the clearly inferior generic products on the market, even those that their company also makes! Their newest branded product is a bargain at ten times the price, even if it's only 5% better than the generic!

The Forest Pharmaceuticals rep who came into our store gave us the schpiel about Lexapro being awesome, but that bothered me a lot less than his pitch for Namenda. He vehemently expressed his opinion that Namenda was the coolest thing in the entire world because "the evidence is so strong for it. I always ask all the doctors who I talk to if they would want the opportunity to add Namenda to their drug regimen if they had Alzheimer's, and they always say, 'well, yes, I would.'"

Background. Namenda is a drug to treat Alzheimer's disease. Wait, I take that back. It's a drug to prevent Alzheimer's disease from getting worse. Wait, no, that's not really true either. It's a drug to make Alzheimer's disease get worse more slowly. That's about right.

The other big drug on the market for Alzheimer's management is called Aricept. You start a patient on Aricept as soon as you suspect they have Alzheimer's, because it works best in mild to moderate cases, but if you don't catch it for some reason, it can work in more severe cases. One study showed an improvement or stabilization of cognitive function in 63% of patients taking it (versus 39% on placebo, not terrible). It's worth a shot to put a patient on Aricept because it's about the best we can do right now.

However, the rep was trying to convince us that Aricept plus Namenda was vastly superior to Aricept alone, saying that there was a whole wealth of evidence available.

The information I've found suggests that the gains on cognitive function scales for treatment with Namenda are roughly a 5% absolute increase. OH MAN. We're still looking at only marginal improvement no matter how we approach drug therapy for Alzheimer's disease. This is totally worth spending an extra $1600 in prescription drug costs a year, considering that Aricept costs about $1700 a year by itself, excluding medical insurance. Behold the power of sarcasm.

Don't come to me and tell me how awesome your drug is unless you're prepared to prove it. And if your drug really isn't all that awesome, quit telling me how awesome it is. The FDA may have approved it because you demonstrated it was better than placebo with studies that showed statististical significance, but don't hype it up when we're talking about 5% absolute gains. I realize that it's the job of people who do marketing to get way more excited about their products than is rational, but this is medicine. That just won't do here.