[Nescafe]

Hi,

I was reading about drug absorption and came across stomach bleeding due to salicylic acid and aspirin.

Based on wiki salicylic acid is considered a weak acid and very little of it is ionized in the stomach (PH 1-2 or 4-5). Aspirin is a weaker acid than salicylic acid.

My question becomes what causes the stomach to bleed?

I read that when a drug is ionized it is soluble and therefore has poor cell permeability. So if this is true, salicylic acid is mainly in its protonated form in the stomach and so is aspirin which is a weaker acid than salicylic acid. So they both cause bleeding because they are somewhat absorbed in the stomach (protonated form, greasy, absorbed.... cause irritation as they penetrate the stomach linings)

But, wiki also states,

"Acetylsalicylic acid is poorly soluble (doesnt this mean it can penetrate the stomach = Bleeding?) in the acidic conditions of the stomach  which can delay absorption of high doses for 8 to 24 hours. In addition to the increased pH (7-8) of the small intestine, aspirin is rapidly absorbed there due to the increased surface area, which in turn allows more of the salicylate to dissolve"

So if I am understanding this correctly, although aspirin passes the stomach linings it is not fully absorbed there but rather when it reaches the intestines.

Does anyone have any info on this?

Thanks,

Nescafe.

[fledarmus]

There are very, very few drugs that are actually absorbed through the stomach lining. Drug absorption takes place through the intestinal lining. In common speech, it is typically referred to as absorption in the gut, and many times (mistakenly) people believe this means the stomach. The stomach is just a chemical processing plant - acids and enzymes are provided to process nutrients into a form that can be absorbed, and the absorption takes place in the intestines.

This was in fact very recently the error that cost a major pharmaceutical company the patent protection on their extended release formulation. I believe it might have been Mucinex? I would have to go back and look it up however. The patent claimed a formulation of the drug that would slowly hydrolyze "so that it could be absorbed in the stomach", and the generic drug maker that copied their drug claimed that it wasn't being absorbed in the stomach but in the intestine. When the drugmaker argued that almost nothing was actually absorbed in the stomach and that "absorbed in the stomach" really meant "absorbed in the intestinal tract", the judge said that since the claim stated stomach, they were stuck with it, and any drug which wasn't absorbed in the stomach did not infringe the patent. No telling how many millions they lost for that little mistake.

[Nescafe]

There are very, very few drugs that are actually absorbed through the stomach lining. Drug absorption takes place through the intestinal lining. In common speech, it is typically referred to as absorption in the gut, and many times (mistakenly) people believe this means the stomach. The stomach is just a chemical processing plant - acids and enzymes are provided to process nutrients into a form that can be absorbed, and the absorption takes place in the intestines.

This was in fact very recently the error that cost a major pharmaceutical company the patent protection on their extended release formulation. I believe it might have been Mucinex? I would have to go back and look it up however. The patent claimed a formulation of the drug that would slowly hydrolyze "so that it could be absorbed in the stomach", and the generic drug maker that copied their drug claimed that it wasn't being absorbed in the stomach but in the intestine. When the drugmaker argued that almost nothing was actually absorbed in the stomach and that "absorbed in the stomach" really meant "absorbed in the intestinal tract", the judge said that since the claim stated stomach, they were stuck with it, and any drug which wasn't absorbed in the stomach did not infringe the patent. No telling how many millions they lost for that little mistake.

Lol. Nice post, they are so screwed =P

But you are not saying that aspirin does not get absorbed through the stomach lining are you? Because there is plenty of evidence that it does and that is why it causes bleeding. But you are right, majority of aspirin/salicylic acid is absorbed in the gut like the others but the issue with aspirin is partial absorption via the stomach with is unfavorable.

Nescafe.

[fledarmus]

Yes, salicylic acid can directly attack the stomach lining and cause bleeding and other forms of gastric distress. Salicyclic acid can penetrate epithelial tissues and break down fats and lipids. It isn't "absorbed" in the stomach per se, it simply damages it. It is quite capable of causing chemical burns on skin or in the stomach. Acetylsalicylic acid does not - it passes through the stomach, is absorbed through the intestines, and is hydrolyzed to salicylic acid by esterases in the bloodstream. This is why acetylsalicylic acid is so much safer to use than salicylic acid. Small amounts of acetylsalicylic acid can be hydrolyzed by the stomach acids as well, and several coated and buffered forms of aspirin have been produced to avoid any hydrolysis of the aspirin before it reaches the intestines.

This is also why you should avoid using very old bottles of aspirin, especially if they smell very strongly of vinegar when you open them up and are soft and powdery. Acetylsalicylic acid will gradually hydrolyze to salicylic acid and acetic acid in moist conditions.

[discodermolide]

As far as I am aware salicylic acid is not readily absorbed by the stomach. Therefore it just stays put for a period go time. As it is a relatively strong acid (but not as compares to the stomach contents) it causes localised damage to the sensitive walls of the stomach, eventually causing bleeding.
Aspirin is more easily absorbed and passes quickly into the gut  and hence the liver where metabolism takes place of the material that is not in the bloodstream.
A very simplified explanation I know, sorry.

[Nescafe]

Thanks for help guys, definitely appreciate it!

Nescafe.