Tylenol.html



Tylenol and Tylenol PM

Tylenol is a North American brand of drugs for relieving pain, reducing fever, and relieving the symptoms of allergies, cold, cough, and flu. The active ingredient of its original, flagship product, acetaminophen (called "paracetamol" outside of North America), is marketed for headaches, fever, muscle and body pain, arthritis, and joint pain. Like the words "acetaminophen" and "paracetamol", the brand name is derived from the chemical name for the compound, N-acetyl-para-aminophenol (APAP). It is available over the counter without prescription, has few side effects, and reacts with very few medications.^{citation needed} However, it can cause liver, kidney, other organ damage, and have fatal interactions with alcohol and other substances, even in the recommended dosages.¹ The brand is owned by McNeil Consumer Healthcare².

History

The active substance of Tylenol, acetaminophen, was first used in medicine in 1894. Acetaminophen only gained widespread use after 1948, when scientists concluded that another popular drug, acetanilide, was toxic and that the same therapeutic effect could be safely achieved with acetaminophen, which was already known to be a metabolite of acetanilide.

James Roth, a U.S. gastroenterologist, advocated paracetamol as a safer alternative to aspirin, which was shown to have some negative effects. Roth was also principal consultant to McNeil Laboratories. In 1953 McNeil Laboratories introduced Algoson, a preparation containing paracetamol together with sodium butabarbital, a sedative. In 1955 McNeil Laboratories introduced Tylenol Elixir for children, which contained paracetamol as its sole active ingredient. It was originally marketed mainly towards children, but soon came to dominate the North American pain-killer market. There are a number of different varieties of Tylenol available today including extra-strength (with 500 milligrams of acetaminophen), children's doses, longer-lasting, and sleep aiding (in combination with diphenhydramine). In 2005 Tylenol Ultra was introduced in Canada, with 500 mg of acetaminophen and 65 mg of caffeine; caffeine has vasoconstricting effects, for which there is some disputed evidence for additional effectiveness.³⁴ The patent on paracetamol has expired, and the continued successes of Tylenol brand preparations are largely due to marketing, the backing of Johnson & Johnson, and new patented delivery mechanisms such as quick-release and extended-release forms of the medication.

On September 29, 1982, a "Tylenol scare" began when the first of seven individuals died in metropolitan Chicago, after ingesting Extra Strength Tylenol that had been deliberately contaminated with cyanide. The crime was never solved and Tylenol sales temporarily collapsed, but the brand was rebuilt and recovered in a few years. At the request of later Chairman, Joseph Chiesa, new product consultant Calle & Company rescued the brand with the invention of the first inherently tamper-proof [enrobed] capsule, Tylenol Gelcaps, recapturing the 92% of capsule segment sales lost after the cyanide incident. The scare led to the introduction of tamper-evident packaging and "gelcaps" across the over-the-counter drug (OTC) and prescription drug industry.

Tylenol remains a top seller, controlling about 35% of the pain killer market in North America.⁵, yet acetaminophen overdose is responsible for more ER visits than any other medicine on the market.⁶

Dangers

See also: Paracetamol#Toxicity

Acetaminophen causes three times as many cases of liver failure as all other drugs combined,⁷ and is the most common cause of acute liver failure in the United States,^{6 8} accounting for 39% of cases. While it occurs through overdosing⁵, even recommended doses especially combined with even small amounts of alcohol, have caused irreversible liver failure^{9 10}

Acetaminophen is metabolized in the liver, resulting in a by-product, N-acetyl-p-benzoquinone imine (NAPQI), that can damage liver cells, but is typically converted into a harmless substance by an antioxidant glutathione. However, large doses of acetaminophen overwhelms the body's supply of glutathione, resulting in destruction of the liver cells. ¹¹

People who have the highest risk for Acetaminophen related kidney failure include: heavy drinkers (three or more drinks per day), elderly men, and persons with pre-existing liver or kidney damage.¹² In infants and small children, studies have indicated that the toxic dose is less than twice the recommended dose.¹³.

A study published by the Journal of the American Medical Association in 2006 suggests problems even in healthy people taking the pain reliever as directed.¹⁴ Healthy adults taking maximum doses of Tylenol for two weeks had abnormal liver test results. Dr. Neil Kaplowitz of the University of Southern California, co-author of the study, said, "I would urge the public not to exceed four grams a day. This is a drug that has a rather narrow safety window..."¹⁵

According to a preliminary study conducted by the University of Washington, mixing acetaminophen and caffeine may cause liver damage, especially in heavy caffeine drinkers. Researchers discovered that caffeine can triple the amount of, N-acetyl-p-benzoquinone imine (NAPQI), the dangerous by product which destroys liver cells. ¹⁶. This reaction can also be casused by large doses of painkillers that combine caffeine and acetaminophen (e.g., Anacin, Excedrin & Midol). These products are often used to treat migraines and menstrual discomfort. Dr. Sid Nelson, a professor of medicinal chemistry at the University of Washington said, "Caffeine can interact with an enzyme that can form a toxic metabolite of acetaminophen in such a way that it increases the formation of that toxic metabolite," ¹⁷

Symptoms from an overdose of acetaminophen typically appear after 24 hours, or in some cases up to 48 hours; however, getting immediate treatment prior to symptoms occurring, can greatly improve the outcome. The antidote to acetaminophen overdose, N-acetylcysteine (NAC), is most effective when taken within eight-hours of an overdose.¹⁸ Due to the delayed symptoms and the importance of immediate treatment, overdoses of acetaminophen kill about 12% of those who seek treatment.⁹ Typical symptoms range from nausea and malaise to extreme upper abdominal pain in the region of the liver.

Tylenol is only one among many popular medications containing acetaminophen, but few users realize that it is contained in hundreds of other pain relievers and cold remedies, and that combined usage has a cummulative effect. Fifteen percent of accidental overdoses involve the simultaneous use of more than one product containing acetaminophen.¹⁹ Products from common brands include acetaminophen: Excedrin, Midol, Theraflu, Alka-Seltzer and NyQuil, as well as prescription narcotics such as Vicodin and Percocet. Following the recommended dosages for each, but in combination can far exceed safe limits for acetaminophen intake.²⁰ The manufacturers of Tylenol recommend, "You should not take two or more products that contain acetaminophen at the same time." ²¹

Tylenol products

Tylenol 3 - a compound of Tylenol (300mg) and Codeine (30mg)

Tylenol sells products to relieve pain, allergies, and cold- and flu- related symptoms. Allergy and cold products also contain dextromethorphan, antihistamines, and expectorants. A class of stronger pain relievers contains codeine: Tylenol 1 (available in Canada without a prescription) contains 325mg acetaminophen, 15mg caffeine and 8mg codeine; Tylenol 2 contains 300mg acetaminophen and 15mg codeine, Tylenol 3 (300mg/30mg), and Tylenol 4 (300mg/60mg). Acetaminophen is also found in other narcotic-based analgesics such as Percocet which contains oxycodone.

Unlike NSAIDs, acetaminophen is not particularly effective against pain from inflammatory disorders, since it doesn't reduce the underlying inflammation.

The normal maximum dose for acetaminophen per day is 65 mg/kg or 4 grams per day, whichever is less. However; there are cases where acute hypotoxicity has been linked to amounts lower than 2.5 grams per day.⁵ Certain patients, such as those taking medications processed by the liver or suffering from diseases of the liver (e.g., Hepatitis A, B, or C), may for safety need to take far lower dosages. Acetaminophen should not be used for over two weeks without seeking medical advice.

It is essential to avoid excessive amounts of acetaminophen as this may cause damage to the liver or kidneys; in particular, users should be aware of the risk of taking different preparations which each contain an acceptable dose of acetaminophen, but which together produce an overdose.

Tylenol PM

Tylenol PM is the trademark for a mixture of paracetamol (acetaminophen) and diphenhydramine, distributed by Johnson & Johnson. It is marketed as a combined analgesic and sedative, or more simply, pain reliever and sleep aid, intended to treat occasional headaches and minor aches and pains with accompanying sleeplessness. It is listed as non-habit forming. Diphenhydramine, which causes drowsiness, it utilized as the sedative. It is an antihistamine utilized as the active ingredient in Benadryl and Benylin, which is used in cough and cold therapy as an anti-cough (anti-tussive) medication.

See also

• List of paracetamol brand names

References

External links

• Tylenol Website
• Pain relief: from coal tar to paracetamol