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Aspirin 81 (2019) (clinicalcorrelations.org)
99 points by hippich on Nov 26, 2023 | hide | past | favorite | 41 comments


I knew it'd be related to a unit conversion after the first paragraph. When regulations require units to be metric, but the actual quantity remains unchanged, this is the result.

Similarly, in the electronics industry, there are connectors whose pitch (distance between pins) is specified as 2.54mm. Not 2.5, but 2.54, which turns out to be exactly 0.1 inches, or "100 thou" in machinist's parlance. Just to add to the confusion, there are also "pure metric" parts originating in the East with exactly 2.5mm pitch, which seems to fit the imperial ones, but only when the pin count is low enough that the difference is within tolerance.

It's worth noting that most if not all of these odd values seem to be metrications of customary units; I can't seem to think of any examples of the opposite.


> It's worth noting that most if not all of these odd values seem to be metrications of customary units; I can't seem to think of any examples of the opposite.

"3.5-inch floppy disks" are actually 90mm (closer to 3.54 in) as they were designed by Sony in Japan


Another place you’ll see weird doses is salts. They have a higher molecular weight than the base chemical. For instance one size is 684 mg Ibuprofen-DL-Lysin. It’s equivalent to 400mg of Ibuprofen.


Interesting they didn't mention the studies of why low-dose gained popularity as some of the initial study amounts were quite high! (up to 1g):

https://www.ctsu.ox.ac.uk/research/british-doctors-study

https://biolincc.nhlbi.nih.gov/studies/cdp/

https://biolincc.nhlbi.nih.gov/studies/amis/

https://www.nejm.org/doi/full/10.1056/nejm198907203210301


This seems to be a US (UK?) thing? At least here in the German speaking countries in Europe aspirin also has nice round numbers. A dosage for heart attack prevention is usually 100mg. Normal dose is 500mg


> UK?

Nope. Just a US thing.

As you can see on the NHS (UK National Health Service) website[1]:

    The usual dose to prevent a heart attack or stroke is 75mg once a day (a regular strength tablet for pain relief is 300mg).
    The usual dose for pregnant women is either 75mg or 150mg, taken once a day.
    The daily dose may be higher, up to 300mg once a day, especially if you have just had a stroke, heart attack or heart bypass surgery.
Also says similar in the BNF (British National Formulary)[2]

[1]https://www.nhs.uk/medicines/low-dose-aspirin/how-and-when-t... [2]https://bnf.nice.org.uk/drugs/aspirin/


That doesn't seem advisable.

It seems like you'd want to base your choice on two main criteria:

1. The lowest effective dosage.

2. The dosage with maximum efficacy vis-a-vis what is studied in the literature.

At a cursory glance, it seems like many studies compare a lower dosage of aspirin to a higher dosage (e.g. 75mg to 300+mg) and the lower dose tends to compare favorably.

Having nice round numbers is of no benefit to a patient.


> Having nice round numbers is of no benefit to a patient.

At our current level of logistical sophistication, the benefit-to-the-patient is that they can get their medications at all.

I agree that in a perfect world every prescription would start with a computation, based on body weight and historical susceptibility and suchlike, to determine precisely the right dosage. However, I also don't think we're there yet. I don't think that you can reasonably prescribe "take 6 milliliters of this" or "take thirteen of these"; patients would mess that up reliably even if they were in perfect health and had perfect vision and perfectly stable hands. And we can't stock thirty different sizes of pill; each size of pill takes up already-limited shelf space, increases cost of packaging and logistics, and increases the likelihood of dosing error. So doctors can't yet prescribe precisely the dosage they should be able to. I'm sure that there are cases where they do - drugs with narrow therapeutic ranges administered in hospital settings where they can be precisely dispensed by IV - but for stuff that's being sent home with patients, we're just not there yet.

(Sadly, even on-demand services like pillpack won't save us, because doctors can't depend on the availability of custom pill-stamping when they make a prescription - they have to assume that the lowest-common-denominator pharmacy is being used to fill the prescription.)

(In fact, going by the rate at which hospital mortality is attributed to dosing errors during administration, we haven't solved precision pharmacology even under ideal circumstances and fundamental breakthroughs are required that will obsolete any current approach to dispensation of prescription medication.)


It’s all “round numbers”. 81mg is just 1.25 grains, a quarter of the normal 325mg dose which is just 5 grains. It’s not like anyone did a clinical study to determine the effective dosage to two significant figures.


>That doesn't seem advisable

Has been working ok for hundreds of millions, so there's that.

Almost all drugs are sold in "nice round numbers" anyway.

Given that you can drop orders of magnitude in scale from grams to milligrams (or whatever) to suite the dosage calculation, nobody is going to notice the difference between X with decimal points and Y which is X rounded, as if 247.3mg was going to be optimal and 250 will be bad.

The variability of what the patient actually needs (e.g. an adult male could be 1.55 and 50kg to 2.10 and 150kg but they usually just get the same dosage in the instructions - and for most drugs no doctor would bother to suggest a more fitting value) would be higher than any rounding error anyway, but in practice it hardly matters.


> Having nice round numbers is of no benefit to a patient.

Patients benefit from simplicity just like practitioners, they have to do math like whether they've reached 1500mg in a day or need to split pills when there is an availability problem (for a dosage.)

An optimal dose to be served to everyone is also a myth as dosing is calculated by weight, etc.


Sure, but it seems like the US is doing the same for all other drugs except for aspirin so I assume it is not a huge problem?


In Ireland, I'm sure I've seen 325mg doses of aspirin and been puzzled by it. I assumed it was just a little bit stronger than paracetamol. While that's probably true, I can see now it's a bit arbitrary too.

Though maybe I'm misremembering or thinking of aspirin someone brought from the US. When I look up one of the most common asiprin brands here, it seems it is 300mg, not 325.

https://phelans.ie/products/dispirin-direct-tablets-24s


They are round units, in a dinosaur apothecary system.

325mg is 5 "grains".

"A grain is a unit of measurement of mass, and in the troy weight, avoirdupois, and apothecaries' systems, equal to exactly 64.79891 milligrams"

https://en.wikipedia.org/wiki/Grain_(unit)

81mg = 1.25 grains.

What ends up happening is a big study is done on an existing formulation of an old drug, results look good, and then you have to ask yourself: do you mess around with the dosing to get a round number, or go with what's been proven?


That’s what the article is all about.


I like this website. All the articles are written by med students. Each one has its own air of "I'm writing this article to impress my professor." It's cute.


This is also sometimes called "baby aspirin".[0]

I remember a conversation with a doctor where I casually mentioned that baby aspirin must have been created for babies, he was slightly aghast and and said no, you do not want to give it to babies!

[0]https://www.nhs.uk/medicines/low-dose-aspirin/who-can-and-ca...


Baby aspirin absolutely was created for babies. Modern doctors are mostly too young to remember that 81mg aspirin was commonly given to babies before the discovery in the 1980s that it was associated with Reye Syndrome.

https://en.wikipedia.org/wiki/Reye_syndrome


You don't want to now, but they did. I remember taking aspirin as a child. Johnsons Baby Aspirin - it dissolved in your mouth and had a slight orange flavor.


Oddly enough, my mom never wanted us to associate medicines with candy, so my brothers and I were given a portion of an adult pill and told to chew it up. Aspirin was bitter, but Tylenol was worse.


Brutal, but effective I suppose. Hopefully she never had to give you anything time released! You do not want to chew them if you plan for them to work in their properly metered delivery.

Fun fact, OxyContin was deemed "impossible to become addicted to" because it incorporated a time-released design that everyone just started chewing up anyway.


Good point, I hadn't thought of that. "Back in my day," there were no time release medicines that I'm aware of. When caring for kids of my own, the kiddie medicines were mostly liquids.


My son hated liquid medicines and quickly learned to be able to take pills instead. It's honestly so convenient that way though.


I remember enjoying those as a kid - I even chewed a few without my parents knowing! In the early 80s, a lot of over-the-counter medication bottles still had minimal to no child-proofing.


Child-proofing or any safety, really. It wasn't until the Chicago Tylenol Murders[1] that they put tamper evident packaging into use.

1. https://en.m.wikipedia.org/wiki/Chicago_Tylenol_murders


That was one incident that impacted just about every single item you find in the supermarket or drug store.

Before that, nobody bothered with inner peel-away caps. Now everything has it. Ketchup has it.


It's kind of mind boggling to me that it took until 1982 for that change to be made. It also makes me wonder how many more poisonings might have slipped under the radar for the same reason...


St. Joseph's Aspirin for Children


That’s it!


> In the apothecary system, the base weight was derived from the weight of a grain of barleycorn.

My god. So not only is shoe sizing done in barleycorns, so is medicine.

https://en.wikipedia.org/wiki/Shoe_size


I just always assumed it was ~1/4 of the normal 325 mg dose.


The article says you are correct, but the original dose is 325mg instead of 300 or 350 because the dose is 5 grains.


Ah I see.


I've never, ever used aspirin in my entire life as far as I recall.

It's an NSAID, right? Which means it's bad for the stomach lining. So when I do have a high fever or a crushing headache, I'll use ibuprofen, which seems to me "stronger" than aspirin (I'm not a doctor, it's just how I perceive it). For short time, several days, and by the end I do feel my stomach saying "no more of this".

And when there's no need for "strong" NSAID, well then I won't use any at all. Maybe use paracetamol.

Either way I never got an use for aspirin.


It's one of a very small number of substances that is proven to reduce heart attack risk, the primary use nowadays. The low dose seems to be a decent balance between that and the increased risk of stomach issues, though only a clear benefit for people with significant risk of cardiovascular events.

If that's not you, then yes, ignore aspirin. If heart attack is how you are almost certainly going to die based on generations of evidence (thanks, Ashkenazi ancestors!) then get to know your favorite brand of 81 mg chiclets, and carry a full pill in your pocket at all times so you can chew it if and when The Thing happens. Better: get a good cardiologist, and do everything they suggest, including the meds. Don't at all listen to people who say that staying in shape and eating healthy is enough, because for those of us with the wrong genes it absolutely is not: I'm young, in great shape, and keep a healthier diet than most dieticians would even suggest, but I still have to take meds to keep my numbers in line.


I just watched a movie that made me reevaluate my choices and career and love life. I know that my mother's family has a history of heart attack. And reading this makes me believe I should take little aspirin daily. I don't want to die.


Subsequent studies have shown that it’s only effective if you’ve already had a cardiovascular event. If you’ve never had one, starting aspirin therapy can actually create more problems that solves.


Entero-aspirin gets it past your tummy intact. Helps.


If anyone else wonders, Aspirin is a trade name for regular ASA (acetylsalicylic acid) painkillers.


The word became the generic in Europe after WW1 and is said to come from the acquisition of Bayer IPR in war reparations.

I think like Thermos and Hoover they just didn't trade mark police adequately.


Likewise “Heroin”. Also an originally a trade name marketed by Bayer & Co.




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