Pain | November 14, 2014 | Author: The Super Pharmacist
Non-steroidal anti-inflammatory drugs (NSAIDs) are chemicals that act as inhibitors of inflammation in the body. Inflammation is associated with a wide range of adverse effects and disorders, including pain, tissue damage, joint deterioration and cancer. Drugs that can prevent the expression of molecules that cause or promote inflammation, essentially a system chemical reaction resulting in the increase of heat or irritation in the affected cells, are beneficial in a number of conditions and illnesses. The most prominent of these are steroids.
Steroids are molecules similar in structure to many hormones and other physiologically active compounds. Therefore, they may have extensive and profound side-effects due to their ability to partially mimic and eventually disrupt the biological effects of hormones. Steroids may cause adverse reactions such as reduced bodyweight control, abnormal emotional or behavioural responses, hypertension and hypogonadism. These drugs may be beneficial in many cases, but are often reserved for advanced or severe illness due to this side-effect profile.
Other drugs with similar properties are available as a more front-line (or over-the-counter) treatment for conditions in which inflammation may be a factor. These mostly fall into the category of non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit enzymes called cyclo-oxygenases. Since these enzymes play an important role of 'pro-inflammatory' biological molecules such as prostaglandins, inhibiting them may significantly reduce inflammation.
Some NSAIDs are among the most popular and established painkillers, and are in very widespread use. An example of this is aspirin, one of the most common drugs taken worldwide. Estimates suggest that approximately 120 billion tablets (at an average of 300mg each) are consumed each year. Other common drugs classed as NSAIDs include:
These NSAIDs are associated with effective treatment of conditions in which pain and/or inflammation are major symptoms. These include:
NSAID use is also associated with a range of side-effects and adverse reactions, some of which overlap with those of steroids (i.e. due to long-term repression of pro-inflammatory molecules). They have been linked to the risk of other adverse effects, which may extend to that of cancer. Recently, NSAIDs were thought to influence the risk of non-Hodgkin's lymphoma. However, studies investigating this link often find no such association.
A systematic review of 17 studies concluded that there was no association between all NSAID types and all subtypes of non-Hodgkin's, and that aspirin use was associated with a reduced risk of one subtype of the condition, chronic lymphocytic leukemia. On the other hand, some of these studies found NSAIDs with the exception of aspirin were associated with the increased risk in women. However, this association may not necessarily be causative; it is likely that these patients were simply taking NSAIDs to alleviate the symptoms of non-Hodgkin's before being diagnosed.
Many studies into this link do not take this into account. Another study including nearly 150,000 participants found an association between NSAIDs and the incidence of non-Hodgkin's lymphoma, but none for most subtypes of the condition - except follicular lymphoma - when this factor was corrected for. In addition, studies on the influence of NSAIDs on the risks of cancer are often not consistent in the patient or demographic groups (for example, patients with rheumatoid arthritis may have an increased risk of cancer that is associated with excess inflammation rather than NSAID use), doses, and duration of drug intake incorporated, making analysis of this association more difficult. In addition, there is evidence that NSAIDs may actually reduce the risks of certain types of cancer, due to their inhibition of prostaglandin synthesis in the body. The risk of the more common side-effects is often influenced by their intake in high doses or over long periods of time.
Liver enzyme elevation is a common adverse effect of many diseases and drugs. In the case of prolonged or high-dose NSAID use, it may indicate additional stress placed on the liver as it tries to maintain the production of the enzymes necessary to adequately metabolise the drugs. In severe cases, this may lead to extensive liver damage.
NSAIDs are thought to affect the health and integrity of the digestive system in two main ways:
Cyclo-oxygenases and prostaglandins play a much more beneficial role when in the gut lining. Chronic NSAID intake may result in many adverse gastrointestinal effects, including;
The risk of these side-effects may be increased by pre-existing conditions in which ulcers and/or bleeding are a component, such as inflammatory bowel disease. Up to 4% of people over 50 who take NSAIDs regularly may experience severe events such as perforation or bleeding. Gastrointestinal side-effects are also associated with the use of steroids.
With the singular exception of low-dose aspirin, regular NSAID use may increase the risk of disorders such as myocardial infarction and stroke. This is influenced by a pre-existing risk for such conditions.
Rofecoxib, an NSAID similar to celecoxib, was found to be associated with a significantly higher rate of myocardial infarction (0.4%) in comparison with that of naproxen (0.1%) and was subsequently removed from the market in the United States. Another large-scale trial investigating the safety of rofecoxib found that it was associated with increased blood pressure in 8% of cardiovascular patients, compared to 1.3% in healthy controls.
Prostaglandins also play a role in the regulation of kidney function, which means their inhibition may increase the risk of renal dysfunction. Some estimates suggest that up to 5% of those taking NSAIDs may develop these kidney problems. These range from fluid retention to sudden-onset kidney failure. The latter may be reversible, but leave the patient at a higher risk of chronic kidney deterioration.
NSAIDs have a high probability of other mild adverse effects, including acute headache and dizziness.
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