Ibuprofen Aspirin

One of the most interesting things about human COX enzymes is that there is more than one of them—definitely two, and probably at least three. This is important to our understanding of the therapeutic effects of ibuprofen, aspirin, and acetaminophen. It had long been suspected that there was more than one COX enzyme, but it was not until 1991 that evidence for the existence of two forms, COX-1 and COX-2, materialized. It was then recognized that COX-1 is present at near constant levels in the body under all conditions (that is, it is a constitutive enzyme), whereas the levels of COX-2 could increase in response to inflammatory conditions (i.e., it is an inducible enzyme). This led to the idea that the side effects of ibuprofen and aspirin (including stomach ulcers) probably arose from inhibition of the constitutive COX-1 enzyme, whereas the therapeutic benefits arose from inhibition of the inducible COX-2 enzyme. 

Kiersch TA, Minic MR. The onset of action and the analgesic efficacy of Saridon (a propyphenazone/paracetamol/caffeine combination) in comparison with paracetamol, ibuprofen, aspirin and placebo (pooled statistical analysis). Curr Med Res Opin 2002 18(l) 18-25. 

As a general precaution, ginkgo biloba may increase the risk of excessive bleeding, especially for people with blood circulation disorders and for those taking ibuprofen, aspirin, or other anti-coagulants. 

Sensitivity to COX inhibitors is rare in children with most reactions occurring to ibuprofen, aspirin, and acetaminophen in that order. Crossreactions between NSAIDs are frequent, but only about 10 % of NSAID-sensitive children react to acetaminophen and all of these patients react to other NSAIDs. 

White, R. P., Robertson, J. T., 1983 Comparison of piroxicam, meclo-fenamate, ibuprofen, aspirin and prostacyclin efficacy in a chronic model of cerebral vasospasm. Neurosurg. 12, 40-46. 

Nonsteroidal Antiinflammatory Drugs. Nonsteroidal antiinflammatory dmgs (NSAIDs) include, among the numerous agents of this class, aspirin (acetylsaflcyhc acid), the arylacetic acids indomethacin and sulindac, and the arylpropionic acids, (5)-(147) and (R)-(148) ibuprofen, (5)-(149) and (R)- (150), flurbiprofen naproxen (41), and fenoprofen (see Analgesics, antipyretics, and antiinflammatory agents Salicylic acid and related compounds). 

FIGURE 25.29 (a) The structures of several commou analgesic agents. Acetaminophen is marketed under the tradename Tylenol. Ibuprofen is sold as Motrin, Nuprin, and Advil, (b) Acetylsalicylate (aspirin) inhibits the cyclooxygenase activity of endoperoxide synthase via acetylation (covalent modification) of Ser ... 

Although extraordinary in its powers, aspirin is also more dangerous than commonly believed. Only about 15 g can be fatal to a small child, and aspirin can cause stomach bleeding and allergic reactions in long-term users. Even more serious is a condition called Reye s syndrome, a potentially fatal reaction to aspirin sometimes seen in children recovering from the flu. As a result of these problems, numerous other NSAIDs have been developed in the last several decades, most notably ibuprofen and naproxen. 

Like aspirin, both ibuprofen and naproxen are relatively simple aromatic compounds containing a side-chain carboxylic acid group. Ibuprofen, sold... 

Aspirin and other NSAIDs function by blocking the cyclooxygenase (COX) enzymes that carry out the body s synthesis of prostaglandins (Sections 7.11 and 27.4). There are two forms of the enzyme, COX-1, which carries out the normal physiological production of prostaglandins, and COX-2, which mediates the body s response to arthritis and other inflammatory conditions. Unfortunately, both COX-1 and COX-2 enzymes are blocked by aspirin, ibuprofen, and other NSAIDs, thereby shutting down not only tire response to inflammation but also various protective functions, including the control mechanism for production of acid in the stomach. 

NSA1D (Chapter 15 Focus On) A nonsteroidal antiinflammatory drug, such as aspirin or ibuprofen. 

As you might expect, percent ionization at a given concentration is directly related to fCa. Ibuprofen (K = 2.5 X 10-5), a weaker acid than aspirin (fCa = 3.6 X 10-4), should be only 3.6% ionized at 0.020 M compared with 12% for aspirin. 

Certain drugs, both prescription and over-the-counter, contain organic acids. Two of the most popular products of this type are the analgesics aspirin and ibuprofen (Advil, Nuprin, and so on). 

Less severe pain states (e.g., arthritis, menstruation, headache, minor surgery) are commonly treated with nonselective NSADDs (e.g., aspirin, ibuprofen, indo-methacin, diclofenac). NSAIDs are mostly used orally. 

NSAIDs are of diverse chemical structures salicylates (aspirin, sulphasalazine), indole acetic acids (indomethacin, etodolac), heteroaryl acetic acids (diclofenac), arylpropionic acids (ibuprofen, naproxen), anthranilic acids (mefenamic acid) and enolic acids (piroxicam, meloxicam). 

There are several hundred reported NF-kB inhibitors (see www.nf-kb.org for a complete and updated list). These inhibitors include natural products, chemicals, metabolites, and synthetic compounds. A large majority of these products, in particular commonly used antiinflammatory drugs such as corticosteroids and the nonsteroidal antiinflammatory drugs (NSADDs) aspirin, sulindac, ibuprofen and sulphasalazine, have the ability to partially inhibit NF-kB activity in cell culture. However, the precise mechanism of action and the specific molecular targets of most of these inhibitors remain unclear. 

Like aspirin, ibuprofen is a nonsteroidal anti-inflammatory drug. It is a cyclooxygenase inhibitor that interferes with COX-1 and COX-2 forms of that enzyme. Its effects on COX-2 give it fever-reducing (antipyretic), analgesic (pain relief), and anti-inflammatory functions. 

The atoms in the molecules of these pain relievers are covalently bonded. Electrons are shared between atoms in a series of single and double covalent bonds. The covalent bonds in aspirin, acetaminophen, and ibuprofen are similar to those found in methane and carbon dioxide. 

Observing and Inferring What structural shape do aspirin, acetaminophen, and ibuprofen have in common ... 

Predicting Predict the possibility of other medicines that might have the same common structural shape as aspirin, acetaminophen, and ibuprofen. 

Ibuprofen 600 mg twice daily for arthritis pain Vitamin B12 once daily Multivitamin daily Aspirin 325 mg once daily... 

Prostaglandins Arachidonic acid/ damaged cells Cyclooxygenase Sensitization Non-steroidal anti-inflammatory drugs (e.g. aspirin, ibuprofen)... 

Another vasoactive substance produced by the endothelium is thromboxane A2 (TxA2). Normally, small amounts of TxA2 are released continuously however, increased synthesis appears to be associated with some cardiac diseases. Synthesized from arachidonic acid, a plasma membrane phospholipid, TxA2 is a potent vasoconstrictor. Furthermore, this substance stimulates platelet aggregation, suggesting that it plays a role in thrombotic events such as myocardial infarction (heart attack). Nonsteroidal anti-inflammatory drugs such as aspirin and ibuprofen block formation of TxA2 and reduce formation of blood clots. 

In addition to their beneficial effects, some medications may actually cause cellular injury and disease. An example of this phenomenon involves nonsteroidal anti-inflammatory drugs (NSAIDS). These drugs include aspirin (a derivative of salicylic acid), ibuprofen (arylpropionic acid, Advil ), and acetaminophen (para-aminophenol derivative, Tylenol ). Because of their beneficial pharmacological effects, consumption of these agents has increased significantly in recent years. NSAIDS have the ability to treat fever, pain, acute inflammation, and chronic inflammatory diseases such as arthritis. They are also used prophylactically to prevent heart disease, stroke, and colon cancer. 

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