Side Effects of Aspirin

Hie bleeding and antithrombotic effects of aspirin are inseperable since both result from platelet inhibition. The bleeding-related side effects associated with aspirin are usually subtle and not recognized in otherwise hemostatically normal individuals (7,8,85,86). In the two aspirin primary prevention trials noted eariier among 22,000 men, 10 severe 

Roth GJ, M erus PW The mechanism of the effect of aspirin on human platdets I. Acetylation of a particulate fraction protein. J. Clin. Invest 624,1975 

RothGJ, StanfordN, MajerusPW Acetylation ofp-ostaglandin synthase by aspirin. Proc. Natl. Acad. Sd. USA 22 3073,1975 

RothGJ, CalverieyDC Aspirin, platelets and thrombosis. Theory and practice. Blood 1 885,1994. 

LitkKP, Overman RS, Sullivan WR, NuebnerCF, ScheeILD Studies on hemorrhagic sweet cJover disease. J. Biol. Chem. 147 463,1943 

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Conversely, certain drugs modify the effectiveness or side effects of aspirin. Phenobarbital, occasionally used for seizures, induces liver enzymes that increase the metabolism and excretion of aspirin, (3-adrenoceptorblocking drugs, such as propranolol, and decrease the antiinflammatory effects of aspirin, whereas reserpine decreases its analgesic effects. Antacids decrease the absorption of aspirin. Alcohol consumption in combination with aspirin increases the latter s ulcerogenic effects. 

Unlike aspirin, acetaminophen does not alter the body s blood-clotting abilities and therefore does not have aspirin s potential benefits in reducing heart attacks and strokes. On the other hand, acetaminophen does not have the toxic side effects of aspirin such as intestinal bleeding and stomach ulcers. However, like most OTC drugs, acetaminophen is metabolized by the liver, and when taken repeatedly in amounts that exceed the recommended dosage, it can cause liver damage. 

Acetaminophen [a seat a MIN oh fen] and phenacetin [fe NASS e tin] act by inhibiting prostaglandin synthesis in the CNS. This explains their antipyretic and analgesic properties. They have less effect on cyclooxygenase in peripheral tissues, which accounts for their weak anti-inflammatory activity. Acetaminophen and phenacetin do not affect platelet function or increase blood clotting time, and they lack many of the side-effects of aspirin. [Note Phenacetin can no longer be prescribed in the United States because of its potential for renal toxicity. However, it is present in some proprietary preparations.]... 

The undesirable side effects of aspirin (ulcers, stomach bleeding) led to the development of other NSAIDs (page 118). Aspirin also has been linked to the development of Reye s syndrome, a rare but serious disease that affects children who are recovering from a viral infection such as a cold, the flu, or chicken pox. Therefore, it is now recommended that aspirin not be given to anyone under the age of 16 who has a fever-producing illness. 

Sarah informs her customer that aspirin is acetylsali-cylic acid and has the chemical formula, C9H8O4. Aspirin is a molecular compound, often referred to as an organic molecule because it contains the nonmetals carbon (C), hydrogen (H), and oxygen (0). Sarah shows her customer the chemical structure of aspirin, and explains that aspirin is used to relieve minor pains, to reduce inflammation and fever, and to slow blood clotting. Some potential side effects of aspirin may include heartburn, upset stomach, nausea, and an increased risk of a stomach ulcer. 

Anti-inflammatory drugs (e.g. aspirin) are beneficial in reducing the pain of arthritis but the side-effect of excess acid secretion is a major problem. Since the drugs are required chronically, there is a risk of development of an ulcer. Unfortunately, a drug that reduced pain of arthritis but minimised acid secretion had severe side-effects and was withdrawn (Chapter 11). 

The arylpropionic acid derivatives are useful for the treatment of rheumatoid arthritis and osteoarthritis, for reduction of mild to moderate pain and fever, and for pain associated with dysmenorrhea. Side effects of the drugs are similar to but less severe than those described for the salicylates. Those who are sensitive to salicylates also may be sensitive to and have adverse reactions when taking ibuprofen and related drugs. Acute hypersensitivity to ibuprofen has been reported in patients with lupus. The hypersensitivity reaction to sulindac can be fatal. The use of sulindac has also been linked to cases of acute pancreatitis. The use of dimethylsulfoxide (DMSO) topically in combination with sulindac has been reported to induce severe neuropathies. The concurrent use of ibuprofen with aspirin reduces the antiinflammatory effects of both drugs. Ibuprofen is contraindicated in patients with aspirin sensitivity leading to bronchiolar constriction and in patients with an-gioedema. As with all NSAIDs, renal and liver function should be normal for adequate clearance of the drugs. 

Derived from the alkaloid thebaine, oxycodone is a highly effective pain-reliever and prescribed to postsurgical patients, cancer patients, and others with severe pain. Oxycodone is sold under various trade names in combination with aspirin, including Per-codan , Endodan, and Roxipirin with acetaminophen it is marketed as Percocet , Endocet, and Roxicet. Oxycodone is also the main ingredient in OxyContin. The most frequent side effect of oxycodone is constipation, but naseua is also common. Oxycodone is highly abused in the United States. 

Most of the nonsteroidal anti-inflammatory drugs (NSAIDs) are carboxylic acids. Aspirin (8.69) (acetylsalicylic acid, ASA) has been used since the turn of the last century to reduce pain and fever, but the parent compound, salicylic acid, has been known and used since antiquity, owing to its common occurrence as a glycoside in willow bark. Acetylation merely decreases its irritating effect. Among the numerous other salicylates known and used, flufenisal (8.70) has a longer duration of activity and fewer side effects than aspirin. Mefenamic acid (8.71) and flufenamic acid (8.72) are derivatives of anthranilic acid, while ibuprofen (8.73) and naproxen (8.74) are derivatives of phenylacetic and naphthylacetic acids, respectively. 

Thus, NSAIDs tend to be differentiated on the basis of toxicity and cost-effectiveness. For example, the gastrointestinal and renal side effects of ketorolac limit its use. Some surveys suggest that indomethacin or tolmetin are the NSAIDs associated with the greatest toxicity, while salsalate, aspirin, and ibuprofen are least toxic. The selective COX-2 inhibitors were not included in these analyses. 

Aspirin (now a generic name) is one of a number of nonsteroidal antiinflammatory drugs (NSAIDs) others include ibuprofen and naproxen (see Fig. 21-15), all now sold over the counter. Unfortunately, aspirin reduces but does not eliminate the side effects of salicylates. In some patients, aspirin itself can produce stomach bleeding, kidney failure, and, in extreme cases, death. New NSAIDs with the beneficial effects of aspirin but without its side effects would be medically valuable. 

Ibuprofen Motrin, many others First nonaspirin NSAID also available in nonprescription form fewer Gl side effects than aspirin but Gl effects still occur in 5°/o-15°/o of patients. 

Since most codeine is dispensed as part of a compound preparation, potential side effects of the other drug(s) must also be considered. For instance, someone with stomach ulcers should not take codeine that is combined with a nonsteroidal anti-inflammatory drug (NSAID) such as aspirin or ibuprofen. Another type of risk from a compound preparation relates to codeine abuse. For instance, a person who abuses codeine might routinely take a dose of 100-200 mg of codeine to produce noticeable euphoria. Using Tylenol 3 to obtain this dose would also mean ingesting 1,000-2,000 mg of acetaminophen. Taking that amount of acetaminophen for any extended period presents a risk for liver damage, especially in combination with alcohol. 

Aspirin, especially when used chronically in geriatric populations, is known for its side effects of GI discomfort and bleeding. Therefore, serum salicylate levels with regular and enteric-coated aspirin were compared in volunteers in a chronic disease hospital and residential home for the elderly [42], It was found that there was no significant difference between the blood levels reached with conventional... 

The addition of ticlopidine to aspirin has been shown to have a synergistic effect on the inhibition of platelet aggregation after stent insertion (6), and this combination has also been found to be superior in terms of prevention of in-stent thrombosis to both aspirin alone and aspirin combined with warfarin (7). However, due to the rare but serious side effect of agranulocytosis associated with ticlopidine (8), and its slow onset of action, ticlopidine is no longer used in most countries. The combination of clopidogrel and aspirin has been proved to be as effective as aspirin and ticlopidine in the prevention of intrastent thrombosis (9). 

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