What Hath Science Wrought?

I'll tell you what, or rather, Decrepit Old Fool will.

Just one more kick in the head to people like Ben Stein who want to throw us all back into the good old Stone Age--without giving up the perks of modernity that they find personally convenient, like cell phones, cars, or antibiotics.

The Price of Potency

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

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

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

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

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

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

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

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

The Future of Automotive Engineering

I couldn't resist sharing this comic I found:

Alternative mechanics ahoy?

Advertising in Bizarro World

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

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

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

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

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

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

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

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

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

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

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

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

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

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

In any case.

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

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

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

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

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

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

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

An Idea

A group of endocrinologists should start a metal band called Thyroid Storm.

Just Pissing It Away

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

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

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

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

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

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

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

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

Really Delayed Ambulance Chasing

A few months ago I was in a minor vehicular accident when traffic ahead of me slowed to a complete stop on the highway. A pickup truck swerved across three lanes and cut in front of me; my eye still on the truck, I failed to notice that the cars ahead had stopped, so I wound up rear-ending a fellow motorist at about five miles per hour as I failed to come to a complete stop. The total damage done was a slight scratch on my front bumper and a tiny imprint the shape of my car in the poor guy's fender. Neither party was injured, so the police didn't even file a full report, just a non-investigated accident form for the both of us as a way of formally exchanging information.

Fast-forward to today, nearly four months later.

When I got home from class, I was told that someone had called about my insurance. Since the other driver had (about a month after the accident) apparently smelled money and tried to claim an injury, I figured that this was about the resolution to that case.

Nope. It was a chiropractor's office.

They were trying to convince me to schedule an appointment in the event that I was having "headaches, backaches, or other pain problems" as a result of the "accident." "It can take several weeks or months for problems to develop," noted the woman on the phone. "This is because at the time of the accident your body is full of all kinds of chemicals."

Right. It still is, as a matter of fact, and I bet I know more about them than she did. Moving on.

I was polite to her; there was no reason to be otherwise, and I declined her offer to make me an appointment for a chiropractic evaluation.

This is all just a story--an anecdote. But I've never seen any other "doctors" having to resort to cold-calling patients from accident records to solicit them as patients. Chiropractors have more in common with ambulance-chasing lawyers than with physicians; the only way most of them are going to get any business is with colorful advertising or by dubious phone-farming.

In retrospect, it might've been somewhat humorous to suggest that I had developed allergies or diabetes since the accident. I wonder what the representative on the phone would've told me if I asked what they could do about it at the office?