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.

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.

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.

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.