Young Australian Skeptics

Here’s a look at a subject that I thought might be timely.

I have a shocking cold/​flu at the moment*. It’s really not fun. So, today, I went out to grab some of ye olde decongestant tablets, and take them… only to realise that, eight hours and six tablets later, my nose is still running as much as ever.

Checking the packet in detail, I realised that I have, for the first time, fallen victim to pharmacology’s answer to the dodgy used-​​car lemon that doesn’t work as advertised. This dodgy lemon is lurking in every pharmacy and supermarket under the guise of medicine — but it’s not homeopathy or bogus herbal medicine. This is actually something which is ostensibly a good, science-​​based pharmaceutical, but in fact it has not, and it has only become widely used due to politics getting in the way of good science-​​based medicine.

(* I actually originally wrote this last year, but never mind.)

That dodgy lemon is a drug called phenylephrine.

Phenylephrine is a drug which is supposed to be useful as an oral decongestant, good for symptomatic relief from colds and flu. The drug has been increasingly common in over-​​the-​​counter medicines over the last few years as a replacement for pseudoephedrine, which is a very effective and useful over-​​the-​​counter medicine for this purpose, but which can be illicitly diverted into the manufacture of the recreational drug methylamphetamine, which it is converted into by means of a relatively straightforward chemical reduction.

Phenylephrine has been making its way into oral cold and allergy medications in response to the perceived “epidemic” of methylamphetamine abuse in Australia (as well as in other Western countries) — but it is typically met with skepticism by pharmacists — because the phenylephrine doesn’t bloody work as a useful medicine in this context. This is the first time I’ve actually been given something by a pharmacist for this purpose which is not psuedoephedrine.

The loser in this war against methylamphetamine abuse will be the general public, if psedoephedrine is pushed out of the over the counter market, as it is doubtful if the legal restrictions on the sale of pseudoephedrine to the public will reduce the availability of methylamphetamine. There is actually little evidence that medicines containing pseudoephedrine are used by large scale producers of methylamphetamine, at least in the United States [1].

The general public — the Australian public, the U.S. public, and everyone else — will be deprived of access to an effective nasal decongestant as pharmaceutical companies and pharmacists are pressured into switching to manufacturing and stocking an ineffective medicine in phenylephrine [1].

There is little if any clinical support for the efficacy of phenylephrine as a nasal decongestant, and its oral bioavailability is quite limited. In contrast, the efficacy of pseudoephedrine as a nasal decongestant is much stronger and its absorption from the gut is uncomplicated [1] [2].

Oral phenylephrine is used as a decongestant, yet there is no published systematic review supporting its efficacy and safety. No support has been found in the literature in the public domain for the efficacy of phenylephrine as a nasal decongestant when administered orally. However, since it’s mainly bioavailability of the drug and its absorption into the body from the GI tract that limits the efficacy of the medicine, it is true that a phenylephrine nasal spray can display some real efficacy for symptomatic relief of nasal congestion associated with a cold or flu.

Phenylephrine is a poor substitute for psuedoephedrine as an orally administered decongestant as it is extensively metabolized in the gut, resulting in very poor oral bioavailability, and its efficacy as a decongestant is unproven [3].

In fact, studies in the USA indicate that restricting the sale of psuedoephedrine to the public as a medicine has had little impact on the morbidity and number of arrests associated with methamphetamine abuse [3].

So, you’re depriving people of legitimate, effective medicine, for legitimate use, and accomplishing nothing as a result.

There is woefully insufficient evidence that oral phenylephrine is effective for nonprescription use as a decongestant, and frankly, that’s not good enough. When people are paying for medicine, by rights, by law, they should be getting a product that actually works. It doesn’t make any difference whether it’s a Supplementary, Complementary or Alternative Medicine (or SCAM for short, if you will), a herbal medicine, or a synthetic pharmacotherapy such as phenylephrine. I apply the same standards to all of them. If there isn’t a good scientific clinical basis for the product to be marketed in a particular context, then it should not be marketed in a particular context.

The Code of Professional Conduct for Australian pharmacists states that a pharmacist must not sell any medicinal product where there is reason to doubt its efficacy. We all expect this to be applied in the context of ear candles and homeopathic remedies, and we really should expect it to be applied in the context of something like phenylephrine, too. The only reason it isn’t, is because science-​​based pharmacy is being subverted by political and law enforcement pressure, due to the “war on drugs”.

It should not be acceptable for a good, effective, proven and safe medicine to be pushed out of the market and replaced with a so-​​called replacement that is no better than a placebo just because it is being pushed by governments and law enforcement agencies as a knee-​​jerk reaction to illicit diversion of pseudoephedrine and amphetamine abuse.

One of the only significant studies that has been performed regarding oral phenylephrine as a nasal decongestant reported that 10 mg of phenylephrine was no more effective than placebo as a nasal decongestant, and a comprehensive recent Cochrane review provides no support for the efficacy of PE. In view of the extensive metabolism of PE in the gut wall, it seems unlikely that PE is an effective oral nasal decongestant [3].

Of course, if you really wanted to, in one fell swoop, completely do away with the whole issue of illicit use of psuedoephedrine as a precursor for methylamphetamine, then all you have to do is market enantiopure (1R,2R)-ephedrine in these medicines — which does have the full pharmacological effectiveness, with zero potential for illicit diversion. The only question is how expensive the enantiopure drug would be.

It begs the question* — will people with a flu pay more for the enantiopure drug if it means they can actually get the drug that is therapeutically effective, with no bullshit, without being treated like criminals?

* Yes, I know, it’s the improper use of the term “begging the question”… but everybody does it.

To end up with the problematic D-​​methylamphetamine, from ephedrine, you need to start from (1R,2S)-ephedrine, or (1S,2S)-(psuedo)-ephedrine — if you started with (1R,2R)-psuedoephedrine or (1S,2R)-ephedrine, then you only end up with L-​​methylamphetamine, if you reduce the stuff. (In case you’re getting confused, they call it psuedoephedrine where both the chiral carbons have the same chirality, and call it ephedrine when they’re different.)

L-​​methylamphetamine is not nearly as addictive or active on the central nervous system as D-​​methylamphetamine, and only exerts effects on the sympathetic nervous system — it is in fact a useful vasodilator and decongestant, but it is completely useless as a recreational drug. The lack of action on the CNS, means, simply, that you don’t get high from it.

Since there are no concerns over illicit diversion of the drug, phenylephrine-​​based products for symptomatic relief from cold and flu are becoming very prominent and widely available on pharmacy and supermarket shelves. But don’t be fooled. You’d be far better off (as is often the case) asking a pharmacist about it, and asking if the product is based on phenylephrine, and if so, is it really proven to be an effective replacement for pseudoephedrine.

At the end of the day, if you ask your pharmacist for a medicine that will really display proven efficicy in this context, they’ll probably just give you the pseudoephedrine anyway, since most pharmacists are well aware of this issue, and want to do the right thing by their customers and patients in terms of delivering effective science-​​based pharmacy to help them feel better.

[1]: http://​www​.bmj​.com/​c​g​i​/​e​l​e​t​t​e​r​s​/​3​3​2​/​7​5​3​8​/​3​82-b

[2]: http://​news​.ufl​.edu/​2​0​0​6​/​0​7​/​1​9​/​d​e​c​o​n​g​e​n​s​ant/

[3]: http://​www​.pubmedcentral​.nih​.gov/​a​r​t​i​c​l​e​r​e​n​d​e​r​.​f​c​g​i​?​a​r​t​i​d​=​2​0​0​0​7​1​1#b8

This entry was posted on Saturday, June 27th, 2009 at 10:00 am and is filed under Luke Weston, Pseudoscience, Skeptic. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.