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The standard protocol for a person experiencing chest pains is to chew a 300mg aspirin tablet, the argument being that chewing rather than swallowing the tablet results in the aspirin entering the blood stream faster.

From a biological standpoint, why is this the case? Given that the stomach and GI tract are specialised tissues to allow for maximum diffusion, why would it be faster to pass aspirin across the gums (bucaal administration?) tongue and cheeks which are not specialised for this purpose?

It is not just a special case for aspirin either, as HypostopTM/GlucogelTM (acute treatment for hypoglycaemic shock, essentially concentrated sugar) is applied directly to the gums or cheek with a similar argument that in critical situations it is faster.

The only suggestion I could find was very vague from the "Merck Manual":

The stomach has a relatively large epithelial surface, but its thick mucous layer and short transit time limit absorption Which I assume could mean that it is the reduced absorption rate in the stomach that makes the oral membranes faster, yet it also says that the delay in the stomach is brief.

I'd be really interested to know the biology behind this!

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I don't have time to write a complete answer now. I will write one out later if no one beats me to it but note that the stomach is not specialized for absorption. Only very limited absorption occurs upstream of the small intestine. The key is that chewing greatly increases the surface area of the tablet, which speeds its dissolution and absorption across the mucosa. – KennyPeanuts Dec 27 '11 at 16:35
Substances absorbed in intestine have to pass through the liver, maybe this cause the delay. See Wikipedia: Hepatic portal system – Marta Cz-C Dec 27 '11 at 16:49
I had not even considered the mechanical action of chewing - how ridiculous! However, it doesn't fully explain the difference as Hypostop is a gel and still preferentially applied directly into the mouth rather than being swallowed. – Rory M Dec 27 '11 at 18:08
why would you by a pound of chopped ice rather than a single 1 pound cube of ice? – shigeta Aug 11 '12 at 18:41
I think surface area is by far the dominant factor: the medical recommendation doesn't say you shouldn't swallow the tablet, only that you should chew it first. A well chewed anything is digested faster than an unchewed anything. – Shep Aug 12 '12 at 13:23
up vote 21 down vote accepted

There are several issues here:

1) Any mucous membrane is a specialized tissue for absorption.

Mucous membranes are indeed not so good for passive diffusion, that makes them absolutely perfect tools for active absorption of certain substances, almost independently from the membrane type. To provide some examples: many drugs like cocaine are inhaled and absorbed in nasal cavities, whereas the rectum is also known and favorite delivery way for medicines.

Generally the absorption force of the mucous membrane is dependent upon how well it is vasculated, for after going through the basal membrane the substance directly enters the blood flow and quickly travels away, thus the concentration gradient on both sides of the basal membrane -- the main barrier in mucosa -- remains relatively high.

See Bhat P. 1995. The limiting role of mucus in drug absorption: Drug permeation through mucus solution for an experimental model for this statement.

2) Mouth mucosa can absorb many substances.

There is a special term called "oral absorption" to describe the rapid drug absorption into blood flow from the mouth cavity. The mucous membrane is not specialized here, but small molecules are able to permeate here through all barriers.

3) Advantages of oral absorption.

There are some:

  • The mucous membrane in the mouth cavity is very highly vascularized. The whole mouth can be seen as a bundle of skeletal muscles and every muscle requires a lot of energy and oxygen, therefore they have one of the highest vascularity rates, having much less distance between single capillaries.

  • Blood flow is higher in the mouth cavity walls than in other inner organs. This is mostly because muscle contractions (during chewing) lead to increased propulsion of blood through capillaries and small vessels here.

  • Any substance that enters blood flow here bypasses the hepatic-portal system. This means that the substance does not have to wait until it is filtered by our liver, it is immediately distributed through the whole body.

  • There are special reflexes from oral mucosa to inner organs. Even not so important in case of aspirin, this is very important for some placebo drugs like methyl valerate (known as "Validol" in many countries) used a lot for treating angina pectoris whose only action is to activate the cold receptors in mouth and thereby leading to reflectory dilating of cardiac vessels.

This is why many drugs, like for example loperamid, are administered only as sub-lingual tablets. And this also explains why in emergency medicine many remedies are injected directly into the tongue.

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"And this also explains why in emergency medicine many remedies are injected directly into the tongue." Ahhhh! – Tim Smith Feb 10 '12 at 23:09

It would also be logical to note that a chewed tablet increases its surface-area-to-volume ratio for absorption relative to an intact tablet, for any absorptive tissue.

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From an engineering point of view, if you chew it the surface area will be enlarged. For example, you take 2 containers with water and 2 tablets which will dissolve in this water. If you crumble one tablet, the take up rate (flux) will be much higher due to the enlarged surface area of the tablet. If you add mixing to the concept, the flux will increase even more. Therefore, in the same amount of stomach fluid there will be a higher concentration of medicine which can be taken up by the body.

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