The over the Counter (OTC) drugs Aspirin and acetominophin (the main active ingredient of Tylenol and other analgesics) are two of the world's best-selling medications of all time. One would hardly be surprised to see this title on an article in the local paper. But what would you say if you read that many people develop liver disease from taking therapeutic doses of these ubiquitous drugs, and that this known side-effect was not mentioned on their labels or accompanying literature?

Although aspirin and acetominophen have a reputation as being generally safe, many people are aware that these non-steroidal anti-inflammatory drugs (NSAIDs) can cause stomach bleeding and are associated with Reye's Syndrome.

Recent studies seem to support the use of daily aspirin in order to reduce the liklihood of heart attack? and strokes.

What about the environmental impact of synthetically producing ?? of tons of the drugs--energy and chemical pollution, and the use of dwindling resources of oil.
Risk to Benefit Ratio

Few people, except the most staunchly holistic of health practitioners, would deny that aspirin or acetominophen[MT1] has some place in the modern medicine. Especially after experiencing a severe toothache or other intractable pain. Pain itself, if it goes on long enough can place a tremendous strain on our energy and immune system reserves. But magic bullets have their pitfalls, too. They seduce us into forgetting why the pain is there in the first place.

Their almost universal occurrence--not only in drug stores, where one might expect them, but in restaurants, gas stations and convenience stores, makes it easy to soothe the ill and forget about the deeper meaning of it all. Why does the toothache occur in the first place? Is it just bad luck that we have weak enamel, or does diet, stress and the overall health of our environment (such as water quality) play a role?

Can milder, but safer (such as willow-bark extract) plant-based medicines offer some relief, as well allow an opportunity to look further into the depths of our pain? Traditional healers, herbalists and other holistic health practitioners might say so. Many pharmacists and doctors would not.

Although these issues appear to be mainly philosophical musings, they are relevant to the central theme of this piece....are aspirin and acetominophen safe, and if not, under what circumstances is the risk worthwhile?

Many scientists are fond of looking at the risk to benefit ratio of a drug, device or method with which to mitigate disease.

To a pharmacist, acetaminophen may help alleviate a headache, toothache, or other pain, thus holding great benefit and little risk. A traditional healer may feel that aspirin only masks the symptoms of a headache and thus does not help a person look at underlying causes, such as job stress, which may eventually lead to more serious illness-thus offering little benefit and possibly important risks.

Recently, common non-steroidal anti-inflammatory agents have shown hepatotoxicity, including acetominophen and aspirin in therapeutic doses.1,2,3,4,5 It has been reported that "about 50% of patients given aspirin regularly in anti-inflammatory doses develop mild, dose-dependent reversible liver damage"

In evaluating comfrey toxicity, one must be conscious of a possible double standard that some pharmaceutical drugs widely sold in drug stores, markets, convenience stores, and many other outlets have been proven to be hepatotoxic. The most common examples are aspirin,6 acetaminophen (as well as common proprietary preparations containing acetaminophen),7 and antibiotics such as tetracycline, erythromycin, and cyclosporin.8,9,10

The main point in assessing the toxicity of both drugs and herbs seems to be the risk/benefit ratio. Although few dismiss the benefit of discriminating use of over-the-counter analgesics, anti-inflammatory agents and antibiotics, the lack of warning on packages and in advertising for these products can be noted.

[**go into several drug stores and take notes on about 6 major brands--do any of them mention liver toxicity?]** report findings**

It is known that children, alcoholics, and people with a history of liver disease are also more susceptible to liver damage from these drugs, but this is not noted on commonly-sold drugs in these categories.11

"About 50% of patients given aspirin regularly in anti-inflammatory doses develop mild, dose-dependent reversible liver damage as shown by elevation of the plasma aminotransferase activity. Liver damage is more severe in a small minority and it may rarely be complicated by disseminated intravascular coagulation and encephalopathy with a fatal outcome (Prescott)."

"In other cases lier damage could have been caused by exposure to other agents, viral infection or naturally occurring liver disease.

Dr. L.F. Prescott, a clinical pharmacologist from the Royal Infirmary, Edinburgh has said that "liver damage has been reported on occasion with virtually all non-narcotic analgesics. Exotic, newer generation drugs in this category, such as diclofenac, glafenine, phenylbutazone can cause liver damage after a short period of use, but Dr. Prescott notes that "paradoxically, it is acetylsalicylic acid (aspirin) and paracetamol (acetaminophen), two of the longest established non-prescription analgesics, which seem to have the greatest potential for hepatotoxicity at present.

Some individuals are especially susceptible to sustaining liver damage from these two drugs, which is usually said to be caused by 'hypersensitivity' or idiosyncrasy.

Besides liver toxicity, regular and heavy consumption of aspirin can also cause other serious problems in susceptable individuals, such as hemorrhage due to the interference of the drug on the vitamin K-dependent synthesis in the liver of clotting factors.

Although aspirin has been used for many years, it is only recently that the hepatoxicity of aspirin has been documented.

**"liver damage does not seem to occur unless salicylate concentrations are maintained for several days or weeks."

Many clinical and laboratory tests have adequately confirmed a close relationship between aspirin ingestion, blood salycilate concentrations and lier damage."