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Aspirin



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.
Aspirin Drug


Low-dose long-term aspirin irreversibly blocks formation of thromboxane A2 in platelets, producing an inhibitory effect 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 and is sometimes called "Junior aspirin." High doses of aspirin are also given immediately after an acute heart attack. These doses may also inhibit the synthesis of prothrombin and may therefore produce a second and different anticoagulant effect.

Several hundred fatal overdoses of aspirin occur annually, but the vast majority of its uses are 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. Because there appears to be a connection between aspirin and Reye's syndrome, aspirin is no longer used to control flu-like symptoms in minors.

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.

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 Acetylsalicylsure; AAS in Spanish- and Portuguese-language countries, for cido acetilsaliclico).


AspirinThe 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). On March 6, 1899 Bayer registered it as a trademark.

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 genericized trademark in a U.S. federal court in 1921. Sterling was ultimately acquired by Bayer in 1994, but this did not restore the U.S. trademark. Other countries (such as Canada and many countries in Europe) still consider "Aspirin" a protected trademark.

How it works

In a piece of research for which he was awarded both a Nobel Prize in Physiology or Medicine in 1982 and a knighthood, John Robert 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 that participates in the production of prostaglandins and thromboxanes, is irreversibly inhibited when aspirin acetylates it. This makes aspirin different from other NSAIDS (such as diclofenac and ibuprofen), which are reversible inhibitors.

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 inhibit only COX-2, with the hope for reduction of 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. Since platelets have no DNA, they are unable to synthesize new COX once aspirin has irreversibly inhibited the enzyme, rendering them "useless": an important difference with reversible inhibitors.

Furthermore, aspirin has 2 additional modes of actions, contributing to its strong analgesic, antipyretic and antiinflammatory properties:

It uncouples oxidative phosphorylation in cartilaginous (and hepatic) mitochondria.
It induces the formation of NO-radicals in the body that enable the white blood cells (leukocytes) to fight infections more effectively. This has been found recently by Dr. Derek W. Gilroy, winning Bayer's International Aspirin Award 2005.
Also, recently aspirin has been proven to prevent carcinoma of the colon, if given in low doses over years.

Indications

Aspirin, as with many older drugs, has proven to be useful in many conditions, and, despite its well-known toxicity, it is widely used, since physicians are familiar with its properties. Indications for its use include:

Fever
Pain (especially useful for conditions involving osteoid osteoma, arthritis and chronic pain)
Migraine
Myocardial infarction prophylaxis (low dose)
Rheumatic fever (drug of choice)
Kawasaki's Disease (along with IVIG)

Contraindications and warnings

Do not take this medicine if you are allergic to aspirin, ibuprofen or naproxen.
Talk to your doctor if your symptoms do not improve after a few days of therapy.
If you have kidney disease, ulcers, mild diabetes, gout or gastritis, talk to your doctor before using this medicine.
Taking aspirin with alcohol increases the chance of stomach bleeding. Avoid alcohol with this medicine.
Giving aspirin to children, including teenagers having a cold or flu can cause a serious condition known as Reye's syndrome.
Patients with hemophilia, other bleeding tendencies, or a bleeding ulcer should not take salicylates.
Some sources recommend that patients with hyperthyroidism avoid aspirin because it elevates T4 levels.

Common side-effects

Gastrointestinal complaints (stomach upset, dyspepsia, heartburn, small blood loss). To help avoid these problems, it is recommended that aspirin be taken at or after meals. Undetected blood loss may lead to hypochromic anemia.
Severe gastrointestinal complaints (gross bleeding and/or ulceration), requiring discontinuation and immediate treatment. Patients receiving high doses and/or long-term treatment should receive gastric protection with high-dosed antacids, ranitidine or omeprazole.
Frequently, central effects (dizziness, tinnitus, hearing loss, vertigo, centrally mediated vision disturbances, and headaches). The higher the daily dose is, the more likely it is that central nervous system side effects will occur.
Sweating, seen with high doses, independent from antipyretic action
Long-term treatment with high doses (arthritis and rheumatic fever): often increased liver enzymes without symptoms, rarely reversible liver damage. The potentially fatal Reye's syndrome may occur, if given to pediatric patients with fever and other signs of infections. The syndrome is due to fatty degeneration of liver cells. Up to 30 percent of those afflicted will eventually die. Prompt hospital treatment may be life-saving.
Chronic nephritis with long-term use, usually if used in combination with certain other painkillers. This condition may lead to chronic renal failure.
Prolonged and more severe bleeding after operations and post-traumatic for up to 10 days after the last aspirin dose. If one wishes to counteract the bleeding tendency, fresh thrombocyte concentrate will usually work.
Skin reactions, angioedema, and bronchospasm have all been seen infrequently.

Overdose

Aspirin overdose has serious consequences and is potentially lethal. Possible effects of overdose include tinnitus, abdominal pain, hypokalemia, hypoglycemia, pyrexia, hyperventilation, dysrhythmia, hypotension, hallucination, renal failure, confusion, seizure, coma and 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.

An acute-overdose patient must be taken to a hospital immediately. Contrary to the urban legend, you can die from eating a bottle of pills, even if you subsequently throw up. Treatment of an acute overdose 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 12 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 glucose 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.

Fifty-two deaths involving single-ingredient aspirin were reported in the United States in the year 2000.

Other useful drug information: Dilantin | Xenical | Mucinex | Tramadol | Adipex | Clonidine | Spironolactone

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Regulatory or medical requirements may wary in different countries, this information is intended for U.S. citizens.

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