Aspirin
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Aspirin or acetylsalicylic acid is a drug in the family of salicylates, often used as an analgesic (against minor pains and aches), antipyretic (against fever), and anti-inflammatory. It has also an anticoagulant (blood thinning) effect and is used in long-term low-doses to prevent heart attacks.
The brand name Aspirin was coined by the Bayer company of Germany. In some countries the name is used as a generic term for the drug rather than the manufacturer's trademark. In countries in which Aspirin remains a trademark, the initialism ASA is used as a generic term (ASS in German language countries, for Acetylsalicylsäure).
Because there appears to be a connection between aspirin and Reye's syndrome, aspirin is no longer used to control flu-like symptoms in children.
Low-dose long-term aspirin irreversibly blocks formation of thromboxane A2 in platelets, producing an inhibitory affect on platelet aggregation, and this blood thinning property makes it useful for reducing the incidence of heart attacks. Aspirin produced for this purpose often comes in 75 or 81 mg dispersible tablets. High doses of aspirin are also given immediately after an acute heart attack.
Several hundred fatal overdoses of aspirin occur annually, but the vast majority of its use is beneficial. Its primary undesirable side effects, especially in stronger doses, are gastrointestinal distress (including ulcers and stomach bleeding) and tinnitus. Another side effect, due to its anticoagulant properties, is increased bleeding in menstruating women.
| Name | acetylsalicylic acid (aspirin) |
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| Systematic name | 2-acetoxybenzoic acid |
| Formula | C6H4(OCOCH3)CO2H |
| Melting point | 136°C (277°F) |
| Boiling point | 140°C (284°F) |
| Structure | Missing image Aspirine-Structure_new.png The structure of the Aspirin molecule |
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.
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History of discovery
Hippocrates, a Greek physician 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.
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.
This chemical was also isolated from meadowsweet flowers (genus Filipendula, formerly classified in Spiraea) by German researchers in 1839. While their extract was somewhat effective, it also caused digestive problems such as irritated stomach and diarrhea, and even death when consumed in high doses. In 1897 one of the researches in the 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. This was the first synthetic drug, not a copy of something that existed in nature, and the start of the pharmaceuticals industry.
Who actually did it is a matter of controversy. Officially, it is claimed that the inventor of aspirin was Felix Hoffmann. On the other hand, Arthur Eichengrün claimed in 1949 that he planned and directed the synthesis of Aspirin while Hoffmann's role was restricted to the initial lab synthesis using Eichengrün's process and nothing more. The Eichengrün version was ignored by historians and chemists until 1999, when Walter Sneader of the Department of Pharmaceutical Sciences at the University of Strathclyde in Glasgow re-examined the case and came to the conclusion that indeed Eichengrün's account was convincing and correct and that Eichengrün deserved credit for the invention of Aspirin. Bayer, however, continues to deny this theory.
It was not until the 1970s that the mechanism of action of aspirin and similar drugs called NSAIDs was elucidated (see below).
History of the name "Aspirin"
The name "aspirin" is composed of a- (from the acetyl group) -spir- (from the spiraea flower) and -in (a common ending for drugs at the time). Bayer registered it 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. The right to use "Aspirin" in the United States (along with all other Bayer trademarks) was purchased from the U.S. government by Sterling Drug, Inc in 1918. Even before the patent for the drug expired 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 subsequently 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 prostaglandins and thromboxanes. This happens because cyclooxygenase, an enzyme which participates in the production of prostaglandins and thromboxanes, is irreversibly inhibited when aspirin acetylates 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. 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 has shown that there are at least two different types of cyclooxygenase: COX-1 and COX-2. Aspirin inhibits both of them. Newer NSAID drugs called COX-2 selective inhibitors have been developed that only inhibit COX-2, with the hope that this would reduce the gastrointestinal side effects.
However, several of the new COX-2 selective inhibitors have been recently withdrawn, after evidence emerged that COX-2 inhibitors increase the risk of heart attack. It is proposed that endothelial cells lining the arteries in the body express COX-2, and by selectively inhibiting COX-2, prostaglandins (specifically PGF2) are downregulated with respect to thromboxane levels, as COX-1 in platelets is unaffected. Thus, the protective anti-coagulative effect of PGF2 is decreased, increasing the risk of thrombus and associated heart attacks and other circulatory problems.
Overdose
Aspirin overdose has serious consequences and is potentially lethal. Effects of overdose include:
- tinnitus
- abdominal pain
- hypokalemia
- hypoglycemia
- pyrexia
- hyperventilation
- dysrhythmia
- hypotension
- hallucination
- renal failure
- confusion
- seizure
- coma
- death
Overdose can be acute or chronic; that is, a person can overdose by taking one very large dose or smaller doses over a period of time. Acute overdose has a mortality rate of 2%. Chronic overdose is more commonly lethal with a mortality rate of 25%. The most common cause of death during an aspirin overdose is noncardiogenic pulmonary edema.
Treatment requires ingestion of activated charcoal to neutralize the acetylsalicylic acid in the gastrointestinal tract, followed by a stomach pump with subsequent re-ingestion of activated charcoal. Patients are then monitored for at least 24 hours and typically given intravenous potassium chloride to counteract hypokalemia, sodium bicarbonate to neutralize salicylate in the blood and restore the blood's sensitive pH balance, and dextrose to restore blood sugar levels. Frequent blood work is performed to check metabolic, salicylate, and blood sugar levels; arterial blood gas assessments are performed to test for respiratory alkalosis and metabolic acidosis. If the overdose was intentional, the patient will undergo psychiatric evaluation as with any suicide attempt.