Aspirin is a brand name coined by the Bayer company of Germany for acetylsalicylic acid, part of the family of salicylates, often used as an analgesic, antipyretic, and anti-inflammatory. Aspirin is a non-steroidal anti-inflammatory drugs (NSAIDs) (see also: ibuprofen, tylenol, vioxx, celebrex, and bextra.
At
one time aspirin was commonly used to control fever and
pain due to flu or the common cold. However because there
appears to be a connection between aspirin and Reye's syndrome,
aspirin is no longer used to control flu-like symptoms.
Low-dose long-term aspirin irreversibly blocks formation
of thromboxane A2 in platelets, producing an inhibitory
affect on platelet aggregation, i.e. blood thinning property,
making it useful for reducing the incidence of heart attacks.
Aspirin produced for this purpose often comes in 75 mg dispersible
tablets. Its primary undesirable side effects, especially
in stronger doses, are gastrointestinal distress (including
stomach bleeding) and tinnitus. Another side effect, due
to is anticoagulant properties, is increased bleeding in
menstruating women. Aspirin was the first discovered member
of the class of drugs known as non-steroidal anti-inflammatory
drugs (NSAIDs), not all of which are salicylates, though
they all have similar effects and a similar action mechanism.
There is evidence that salicylates in past ages were much
more common in human diets than they are now. Salicylates
are produced by fruit as a defence mechanism: inducing damaged
and diseased cells to commit suicide. Modern man's predilection
for fruit and vegetables in a pristine condition - with
shoppers often rejecting fruit with bumps of bruises - means
that we eat less salicylates than in the past. A study has
shown that organic vegetable soups contain nearly six times
as much salicylate as non-organic equivalents (European
Journal of Nutrition, vol. 40 p 289). There are moves
to have aspirin declared a vitamin, vitamin S, rather than
a drug, though more research is needed to establish whether
our diets are salicylate-deficient, resulting in higher
levels of heart disease, cancer and Alzheimer's disease,
than would be the case if everyone routinely took salicyalte
supplements.
Hippocrates,
a Greek for whom the Hippocratic Oath is named, wrote
in the 5th century BC about a bitter powder extracted
from willow bark that could ease aches and pains and reduce
fevers. This remedy is also mentioned in texts from ancient
Sumeria, Egypt and Assyria. Native American Indians used
it for headaches, fever, sore muscles, rheumatism, and
chills. The Reverend Edmund Stone, a vicar from Chipping
Norton in Oxfordshire England, noted in 1763 that the
bark of the willow was effective in reducing a fever,
but his reasoning for that was very much in error.
The
active extract of the bark, called salicin, after the
Latin name for the white willow (Salix alba), was isolated
to its crystaline form in 1828 by Henri Leroux, a French
pharmacist, and Raffaele Piria, an Italian chemist, who
then succeeded in separating out the acid in its pure
state. Salicin is highly acidic when in a saturated solution
with water (pH = 2.4), and is called salicylic acid for
that reason. Salicylic acid's systematic name is 2-hydroxybenzoic
acid.
This
chemical was also isolated from meadowsweet flowers (Latin
name spiraea) by German researchers in 1839.
While somewhat effective, it also caused digestive problems
such as irritated stomach and diarrhea. It can even cause
death in high doses. In 1897 Felix Hoffmann, a chemist
working for Friedrich Bayer & Co. in Germany, derivatized
one of the hydroxyl functional groups in salicylic acid
with an acetyl group (forming the acetyl ester) which
greatly reduced the negative effects. The new product,
named a- (for the acetyl group) -spir- (for the flower)
-in (a common ending for drugs at the time), had fewer
side effects and was more effective than salicin or salicylic
acid. This was the first synthetic drug, not a copy of
something that existed in nature, and the start of the
pharmaceuticals industry. Bayer registered aspirin as
a trademark on March 6, 1899.
However, the German company lost
the right to use the trademark in many countries as the
Allies seized and resold its foreign assets after World
War I. In the United States, the right to use "Aspirin"
there (along with all other Bayer trademarks) was purchased
from the U.S. government by Sterling Inc in 1918. Even
before the patent went into the public domain in 1917,
Bayer had been unable to stop competitors from copying
the formula and using the name elsewhere, and so with
a flooded market, the public was unable to recognize "Aspirin"
as coming from only one manufacturer. Sterling was subsquently
unable to prevent "Aspirin" from being ruled a generic
mark (and therefore unprotected) in a U.S. federal court
in 1921. Other countries (such as Canada) still consider
"Aspirin" a protected trademark.
How
it works
In
a piece of research for which he was awarded both a Nobel
prize and a knighthood, John Vane, who was then employed
by the Royal College of Surgeons in London, showed in
1971 that aspirin suppresses the production of local hormones
known as prostaglandins. Cyclooxygenase, an enzyme which
participates in the production of prostaglandins and thromboxanes,
is irreversibly inactivated when aspirin attaches to it.
Prostaglandins
are local hormones (paracrine) produced in the body and
have diverse effects in the body, including but not limited
to transmission of pain information to the brain, modulation
of the hypothalamic thermostat and inflammation. Additionally
thromboxanes are responsible for the aggregation of platelets
that form blood clots. Heart attacks are primarily caused
by blood clots, and their reduction with the introduction
of small amounts of aspirin has been seen to be an effective
medical intervention. The side effect of this is that
the ability of the blood in general to clot is reduced,
and excessive bleeding may result from the use of aspirin.
More
recent work by M.G. Santoro has demonstrated that there
are several types of prostaglandins. Those, such as the
A, E and J12 type induce cell protective proteins, especially
HSP, which aspirin blocks in addition to the prostoglandins
associated with inflamation. In some auto-immune diseases,
these other prostiglandins are excessively produced. The
concept of cox 1 and cox 2 blockers was an attempt to
block only the inflamitory causing prostaglandins. Recent
work on other intra-cellular proteins have found other
inflamitory causing substances not blocked by aspirn,
such as fKb protein. The door Dr. Vane opened is proving
to be a gateway to a still hardly understoon mircoworld.