Why would there be caffeine in my aspirin? Or sodium?

[SmackFu]

My generic aspirin says it's caffeine-free and sodium-free on the label. Why would they be in there in the first place?

Should I seek out some caffeinated salty aspirin?

[tanstaafl]

Quite a few pain killers contain caffeine. I know its in BC Powder.

Just checked. Yep.
BC® POWDER: Active Ingredients: Each powder contains Aspirin 650 mg, Salicylamide 195 mg and Caffeine 33.3 mg.

Caffeine apparently has some analgesic effect of its own, so lots of aspirin type medicines have it.

[Q.E.D.]

Dunno about sodium, but caffeine acts in concert with aspirin or acetaminophen to combat pain more effectively than either analgesic alone.

[Exapno Mapcase]

The entire reason for the existence and heavy long-term advertising of Excedrin is that is adds caffeine to otherwise generic aspirin and acetaminophen and so can sell for many times the price.

[KneadToKnow]

Exapno, it also helps build a loyal clientele out of people like me who can't tell the early stages of a migraine from a caffeine withdrawal headache. :)

[Qadgop the Mercotan]

Caffeine is an analgesic adjuvant (http://www.ncbi.nlm.nih.gov/pubmed/2012456). Studies show it does make aspirin, and other pain relievers, more effective.

Not sure what role sodium plays, but it probably stabilizes the compound.

[Celyn]

Wow, I never knew that: I always just assumed, in my cynical way, that adding caffeine was just a bit of a cheat to make people feel perkier and therefore impressed that their aspirin worked, and thought I was being very smart and clever to stick to cheap generic aspirin. More ignorance fought, then. :)

[gotpasswords]

Caffeine is an analgesic adjuvant (http://www.ncbi.nlm.nih.gov/pubmed/2012456).
Another nine-dollar word you'll run into for this is that caffeine will potentiate the analgesic. In other words, it has a synergistic, or multiplying effect on the effectiveness of the aspirin or whatever the base painkiller is.

[hajario]

The entire reason for the existence and heavy long-term advertising of Excedrin is that is adds caffeine to otherwise generic aspirin and acetaminophen and so can sell for many times the price.

I suffer from something called atypical migraines. My mom, sister and uncle get them as well. The only thing that helps us is Excedrin. That stuff is a life saver. There is a generic form of Excedrin by the way. It's called EPF or something like that. They stock it in the medicine cabinet at work.

[RealityChuck]

Another nine-dollar word you'll run into for this is that caffeine will potentiate the analgesic. In other words, it has a synergistic, or multiplying effect on the effectiveness of the aspirin or whatever the base painkiller is.Interesting, since Excedrin went to great lengths never to make that claim, and you'd think they'd be shouting it out.

Their claim was that the caffein may make the aspirin more effective, not that it did.

[mnemosyne]

The sodium is usually present as part of a filler compound; something that's in there to help add bulk, or a binding agent, or whatever. In many formulations, the chemists had a choice of creating the pill with various types of salts, either sodium-whatever, calcium-whatever, magnesium-whatever(2), etc. Offhand, I'm not comfortable giving actual examples used in pharmaceuticals, since I'm very tired and I don't want to make a mistake!

If the stability/bioefficacy/clinical etc testing showed no particular difference between one formulation or another then they might choose to go with the one without sodium, since sodium has associated health issues (keep in mind that many, many different versions of a drug might be tested... I once worked on a project where they were weeding it down to one marketable pill from 12 different recipes, only varying in the non-active ingredients!)

A similar thing goes for lactose; if you can make your pill without it, then the very, very very few people who react badly to such a miniscule amount of lactose become possible customers. Being lactose-free also makes it easier to certify the pill as being kosher, though most companies never bother doing so because of the cost and PITA involved, unless the drug ends up OTC... there's some value to that.

[Vox Imperatoris]

I had always heard that the caffeine expands your blood vessels and makes the pain reliever move through them faster. Is this incorrect?

Valete,
Vox Imperatoris

[Hunter Hawk]

Caffeine is an analgesic adjuvant (http://www.ncbi.nlm.nih.gov/pubmed/2012456). Studies show it does make aspirin, and other pain relievers, more effective.
Is it only the pain-relieving properties of aspirin that caffeine affects? (What happens if someone is taking aspirin for "heart health"?)

[Turek]

I had always heard that the caffeine expands your blood vessels and makes the pain reliever move through them faster. Is this incorrect?

Exactly opposite. Caffeine is a vasoconstrictor.

[Colophon]

The sodium is usually present as part of a filler compound; something that's in there to help add bulk, or a binding agent, or whatever.
Not exactly. But what you said in the next sentence is closer to the mark:
In many formulations, the chemists had a choice of creating the pill with various types of salts, either sodium-whatever, calcium-whatever, magnesium-whatever(2), etc. Offhand, I'm not comfortable giving actual examples used in pharmaceuticals, since I'm very tired and I don't want to make a mistake!
Aspirin is acetylsalicylic acid, a modified form of salicylic acid (which is found in willow bark). However, the acid by itself is not very soluble, so to make soluble aspirin, it is sold as the sodium salt, sodium acetylsalicylate, which is much more soluble in water.

Normal, non-soluble, aspirin, however, wouldn't normally have sodium in it anyway, so I think it's just marketing.

[Szlater]

Not exactly. But what you said in the next sentence is closer to the mark:

Aspirin is acetylsalicylic acid, a modified form of salicylic acid (which is found in willow bark). However, the acid by itself is not very soluble, so to make soluble aspirin, it is sold as the sodium salt, sodium acetylsalicylate, which is much more soluble in water.

Normal, non-soluble, aspirin, however, wouldn't normally have sodium in it anyway, so I think it's just marketing.

Is the sodium salt more stable than the acid?

Also, even in non-soluble aspirin wouldn't a higher solubility increase the uptake of the drug and speed its effects?

[WarmNPrickly]

I think the sodium salt would be less stable. The acetyl group will hydrolyze under mildly basic conditions. Also, once it gets to the stomach acid, it's as good as protonated. Maybe there is some small absorption difference, but I suspect it gets protonated the instant it hits the stomach. Using the sodium salt may make it more comfortable to take as it travels to the stomach.

I looked for evidence that they used sodium acetylsalicylate, but couldn't find any specific formulation that said they did. I suspected that Bufferin did, since I assume the name is derived from acid-base buffer which is what the salt would be if it were partially protonated.

[Szlater]

I think the sodium salt would be less stable. The acetyl group will hydrolyze under mildly basic conditions. Also, once it gets to the stomach acid, it's as good as protonated. Maybe there is some small absorption difference, but I suspect it gets protonated the instant it hits the stomach. Using the sodium salt may make it more comfortable to take as it travels to the stomach.

I looked for evidence that they used sodium acetylsalicylate, but couldn't find any specific formulation that said they did. I suspected that Bufferin did, since I assume the name is derived from acid-base buffer which is what the salt would be if it were partially protonated.

I was thinking stability in storage rather than when it's taken.

[WarmNPrickly]

I was thinking stability in storage rather than when it's taken.

Yes, that's what I meant. Like I said, your stomach is acid so not mildly basic. The real problem would be humidity. As for other decomposition processes, I have no idea.

ETA: I think my paragraph structure is confusing in the first response.

[FatBaldGuy]

When I was a kid (back in the 50's), my dad was in the military and we would often go to the base hospital for any kind of medical treatment.

I remember for various aches and pains they would give us pills called APC. I know the "A" and "C" were for aspirin and caffeine (or maybe codeine?), but I'm not sure what the "P" stood for.

Also, I don't know if this was common medicine at the time, or if it was mostly used in the military, or why it's not common any more. I'm assuming that acetaminophen and ibuprofen have supplanted its use.

Anyone else remember using APC for pain relief?

[Nava]

Caffeine is an analgesic adjuvant (http://www.ncbi.nlm.nih.gov/pubmed/2012456). Studies show it does make aspirin, and other pain relievers, more effective.

Not sure what role sodium plays, but it probably stabilizes the compound.

Aspirin is o-acetyl-salicylic acid (I may have gotten an y or i wrong there). No cite here, but there's a notion that some of the stomach problems sometimes associated with aspirin intake are lessened by taking it in a tamponated or basic form. The tampon form would be a mixture of the acid and its sodium salt; the basic form is the sodium salt. Both exist as OTC medication in Spain, I don't know about the USA.

Why sodium, and not lithium or potasium? Because sodium is lots cheaper, and it's considered sort of "neutral for anybody who doesn't have HBP problems". If anybody was to make a mixture involving the lithium salt, they'd want to be able to claim it's good for the blues; if they were to involve the potassium salt, they'd want to be able to say it's good for HBP. But in order to make such claims, they'd need to finance appropiate studies. Nobody is going to use the more expensive version when all it represents is a financial loss.

That's on top of the solubility issue, which would also be affected by the metal used.

[Szlater]

but I'm not sure what the "P" stood for.


Phenacetin (http://en.wikipedia.org/wiki/Phenacetin) apparently.

[ftg]

Interesting, since Excedrin went to great lengths never to make that claim, and you'd think they'd be shouting it out.

Count me as surprised as well. IIRC the phrase they use in their ads is ~ "plus an extra ingredient that may help it work better." "May"??? If there is any fraction of a shred of a suggestion that something might really work, drug companies wouldn't be dancing around it.

[Nava]

Another question would be "why do these people feel the need to indicate that their aspirin is sodium-free and caffeine-free?"

The answer would be the same as for "why is there such a thing as people like my coeliac boss who, after years of buying any brand of rice, is now buying the one where someone from marketing thought of putting a sticker that says 'adequate for coeliacs'." She also buys "adequate for coeliacs" gummy bears, sunflower nuts and potato chips. She refuses to buy anything made with corn which doesn't specifically say "adequate for coeliacs" because "they may have ground wheat in the same mill, leading to contamination." When we go to a restaurant, she claims that she can't have anything with sauces, instead of "I can't eat any sauces that contain flour." And, judging by the amount and kinds of "adequate for coeliacs" labels I'm seeing, she's not the only one who goes through life like that.

The "no caffeine" and "no sodium" labels are there for people who think that any item contains their dietary foe unless the item's label explicitly states that it doesn't.

[Szlater]

Count me as surprised as well. IIRC the phrase they use in their ads is ~ "plus an extra ingredient that may help it work better." "May"??? If there is any fraction of a shred of a suggestion that something might really work, drug companies wouldn't be dancing around it.

You can't make a claim about efficacy without having trial data to back it up, using "may" would probably sidestep that requirement.

[Szlater]

Another question would be "why do these people feel the need to indicate that their aspirin is sodium-free and caffeine-free?"

The answer would be the same as for "why is there such a thing as people like my coeliac boss who, after years of buying any brand of rice, is now buying the one where someone from marketing thought of putting a sticker that says 'adequate for coeliacs'." She also buys "adequate for coeliacs" gummy bears, sunflower nuts and potato chips. She refuses to buy anything made with corn which doesn't specifically say "adequate for coeliacs" because "they may have ground wheat in the same mill, leading to contamination." When we go to a restaurant, she claims that she can't have anything with sauces, instead of "I can't eat any sauces that contain flour." And, judging by the amount and kinds of "adequate for coeliacs" labels I'm seeing, she's not the only one who goes through life like that.

The "no caffeine" and "no sodium" labels are there for people who think that any item contains their dietary foe unless the item's label explicitly states that it doesn't.


I wonder how much of her life before labelling consisted of "coeliac roulette". If I had a condition that required me to watch out for certain things for fear of unpleasant effects, I would probably avoid anything not labelled because of the peace of mind it would give to be able to eat something without the thought of "will this make me sick" hanging in the back of my mind.

When I had gallstones I was very careful about avoiding any foods that contained fat. I never had an episode of biliary colic when I followed that plan. Deviating from it though (which I had to on vacation) became an unpleasant lottery, which spoilt my fun even when I didn't have an attack, as I was constantly worrying whether I would shortly be doubled up in pain on the floor of the restaurant.

[MikeS]

I remember for various aches and pains they would give us pills called APC. I know the "A" and "C" were for aspirin and caffeine (or maybe codeine?), but I'm not sure what the "P" stood for.

Also, I don't know if this was common medicine at the time, or if it was mostly used in the military, or why it's not common any more. I'm assuming that acetaminophen and ibuprofen have supplanted its use.Phenacetin (http://en.wikipedia.org/wiki/Phenacetin) apparently.Note that phenacetin is chemically very closely related to acetaminophen (http://en.wikipedia.org/wiki/Paracetamol) (replace a hydroxyl group with an ethoxyl), which is probably why it has largely supplanted phenacetin.

[mnemosyne]

Not exactly.

For some reason, the only excipient names I can think of right now are magnesium stearate and lactose... neither of which contain sodium! I'm not aware of sodium stearate being used in pharmaceuticals, though it is used in detergents (perhaps in some form of extended-release mixture? I have no idea).

I used to know the ingredients to 6 different versions of an under-development drug (not yet on the market), but I can't seem to remember them at all now (it's been 2.5 years since I worked at that company!) I could have sworn one of them was a sodium salt.


The "Excipients" wiki lists the following soldium salts:
sodium starch glycolate
sodium carboxymethyl cellulosemethycellulose (?!?)
sodium citrate (--that's the one I was looking for above!!)

And I suppose sodium benzoate could be counted as well, though it's mostly used in syrups and, IIRC, injectables.

[Fritz]

When I was a kid (back in the 50's), my dad was in the military and we would often go to the base hospital for any kind of medical treatment.

I remember for various aches and pains they would give us pills called APC. I know the "A" and "C" were for aspirin and caffeine (or maybe codeine?), but I'm not sure what the "P" stood for.

Also, I don't know if this was common medicine at the time, or if it was mostly used in the military, or why it's not common any more. I'm assuming that acetaminophen and ibuprofen have supplanted its use.

Anyone else remember using APC for pain relief?
Yup. A long time ago. Don't know what the "P" stands for either.

On preview, looks like MikeS got it.

[Solfy]

I was thinking stability in storage rather than when it's taken.

I've never encountered any storage issues when keeping sodium or other salts of active pharmaceuticals vs their "free" form. It may explain the tiny vial of dessicant in my Excedrin, though.
As an added bonus, "salting" a molecule frequently makes it many times easier to isolate as a crystalline solid.

[Kuboydal]

I have become a fan of Alka Seltzer, the first aspirin I have ever taken apart from once as a child. I was introduced to the lemon lime flavored variety but substituted the original formula when I could not find what I liked. It was extraordinarily salty. Can citrus chemicals replace whatever function was originally played by the salt?

I like that the label suggests its use for the problems often associated with overindulgence.

[gravitycrash]

I can't explain why Excedrin works for me and other medications with the same ingredients and same dosage don't do as well for me. I wish I could but it knocks my headache out in about 20 minutes. I'll pay the extra costs gladly.

I wish I had a factual answer. Better processing of the drugs maybe? Perhaps Qadgop can clear things up a little.

[The Mermaid]

Note that phenacetin is chemically very closely related to acetaminophen (http://en.wikipedia.org/wiki/Paracetamol) (replace a hydroxyl group with an ethoxyl), which is probably why it has largely supplanted phenacetin.

More likely the P stands for Paracetamol (http://en.wikipedia.org/wiki/Paracetamol) also known as acetaminophen which is cheap and plentiful.

[mks57]

Anyone else remember using APC for pain relief?

I remember people saying that it stood for "All-Purpose Cure". It's what the medics handed out for minor illnesses.

[Nava]

I wonder how much of her life before labelling consisted of "coeliac roulette". If I had a condition that required me to watch out for certain things for fear of unpleasant effects, I would probably avoid anything not labelled because of the peace of mind it would give to be able to eat something without the thought of "will this make me sick" hanging in the back of my mind.

When I had gallstones I was very careful about avoiding any foods that contained fat. I never had an episode of biliary colic when I followed that plan. Deviating from it though (which I had to on vacation) became an unpleasant lottery, which spoilt my fun even when I didn't have an attack, as I was constantly worrying whether I would shortly be doubled up in pain on the floor of the restaurant.

Ingredients: potatoes, salt, sunflower oil.

That's a list which is perfectly appropiate for coeliacs. There is only four things they need to avoid. My Dad had a bad reaction to mushrooms (they made him drunk): once they figured out that he couldn't eat mushrooms, nor anything that had been cooked with mushrooms, he just avoided mushrooms. He didn't need a label saying "appropiate for mushroom-sensitives" on, say, pizza margarita. I'm lactose intolerant, Middlebro can't have capsaicins, Mom's forbidden list looks like a school roster.

Sheboss, otoh, won't eat something with an ingredients list of "potatoes, salt, sunflower oil" unless there is an additional label that says "adequate for coealiacs." The ingredients list still says "potatoes, salt, sunflower oil".

[teela brown]

I think if aspirin or other analgesics had never been discovered, caffeine would be popular as a headache remedy.

I often wake up with a headache in the mornings, and I hold off taking any aspirin or ibuprofen until after I've drunk coffee. Nine times out of ten, the coffee quickly dissipates the headache and there's no need for any further remedy.

[Canadjun]

More likely the P stands for Paracetamol (http://en.wikipedia.org/wiki/Paracetamol) also known as acetaminophen which is cheap and plentiful.

I doubt it. I'm sure someone will correct me if I'm wrong, but I don't believe the word paracetamol (instead of acetaminophen) is in common use anywhere in North America - the word is used in Britain (and I assume Europe?), and I have certainly seen APC here (not in a very long time, but I have seen it). No cites, but my recollection also is that the P is Phenacetin. Anybody got a bottle of the stuff?

PS I vaguely recall seeing APC & C (the second C for codeine) as well, but I'm less confident of that recollection.

[mnemosyne]

I think if aspirin or other analgesics had never been discovered, caffeine would be popular as a headache remedy.

I often wake up with a headache in the mornings, and I hold off taking any aspirin or ibuprofen until after I've drunk coffee. Nine times out of ten, the coffee quickly dissipates the headache and there's no need for any further remedy.

Would that headache not be caused by the caffeine withdrawl, and therefore you are simply treating that symptom, rather than "curing" a headache from another cause?

I don't drink coffee and don't know the mechanism of caffeine addiction, but I have known people to have headaches or other symptoms when they skipped their regular coffee breaks/times.

[teela brown]

Would that headache not be caused by the caffeine withdrawl, and therefore you are simply treating that symptom, rather than "curing" a headache from another cause?



Nope. After a mostly headache-free youth, I started developing nighttime and morning headaches in the last couple of years. Doc says it's menopause-related. Although I do get the caffeine-withdrawal headaches you mention if I start on a campaign of cutting back on coffee drinking for any reason. Those headaches are really, really bad news.