Prescription NSAIDS in Pain Management

NSAIDs are nonsteroidal anti-inflammatory agents. Non-prescription NSAIDs include ibuprofen and naproxen.  Even aspirin and willow bark are considered NSAIDs. They have been used by people since the early 1900s (willow bark has actually been used a lot longer in alternative medical circles and by lay people).  Aspirin was first introduced into the market in 1899. 

COX-2 inhibitors are another, more recent class of medications, used by prescription as nonsteroidal anti-inflammatory agents.  Because they are new, long term implications of using these types of drugs have not been studied and this is being studied. 

NSAIDs have many uses when it comes to pain.  They reduce inflammation, decrease stiffness, decrease fever, and lessen platelet aggregation.  NSAID use is very common, with about 50-100 million prescriptions being prescribed each year and an untold number of patients taking the drug as a non-prescription treatment.  The overall cost of these medications in the US is about one billion USD per year, although others estimate the cost can be as high as $2.2 billion per year. 

Inflammation involves the processes of tenderness, redness, swelling and pain.  It can be caused by an injury, ischemia or an infection.  There are actually three phases to inflammation.  The first phase is when you experience the symptoms of redness, swelling, and pain.  This is caused by dilatation of the vessels around the site of the injury and leakage of fluid and inflammatory molecules around the site.  The next phase of inflammation is when inflammatory cells and macrophages travel to the injured site to get rid of dead cells and fight bacteria.  The last phase of inflammation is when connective tissue comes in to create a scar and healthy tissue is regenerated. 

Acetaminophen is a good drug for fever but is not considered to be an NSAID.  This is because it has no effect on platelets nor does it affect inflammation.  Unlike NSAIDs, acetaminophen carries a greater risk of damage to the liver.  It can be used in those who cannot tolerate NSAIDs for whatever reason.  Because it does not affect inflammation, it should not be used when there is a significant amount of inflammation associated with a pain.  Instead of acting as an anti-inflammatory, acetaminophen, marketed as Tylenol®, acts on the fever centers of the hypothalamus.  It increases sweating, promoting a decrease in body temperature.  Its effectiveness on controlling pain isn’t understood very well. 

Aspirin and other salicylates metabolize in the body into salicylic acid.  Aspirin is the only NSAID that actually acts on platelets, while all NSAIDs act on pain and inflammation.  Salicylates actually go to the site of inflammation in order to work.  They block prostaglandin synthesis, which causes pain and inflammation.  The antiplatelet activity happens because aspirin acetylates COX (cyclooxygenase), This causes a decrease in thromboxane A2, which causes platelets to stick together.  Aspirin also blocks prostaglandin synthesis, which acts directly on the hypothalamic fever centers, decreasing fever.  It also causes dilatation of the blood vessels of the body, causing a decrease in body temperature. 

Other NSAIDs act a bit differently from aspirin but basically do the same things (except inhibit platelet aggregation).  They can be even stronger than opioids in some cases, especially for pain following surgery.  There are several classes of NSAIDs.  The one most people take over-the-counter is propionic acid. This includes naproxen and ibuprofen, along with prescription drugs ketoprofen, oxaprozin and fenuprofen.  COX-2 inhibitors are another common class of NSAID.  This includes celecoxib and rofecoxib. They are easier on the stomach when compared to other nonsteroidal agents.  It is a sulfonamide-type medication, meaning that it cannot be taken by people known to have sulfonamide allergies.  Interestingly, those people who are allergic to aspirin need to avoid taking all types of NSAIDs, even those that are not salicylates. 

Anti-inflammatories all inhibit cyclooxygenase or COX.  There are two types of COX: COX-1 and COX-2.  Both types of enzymes block the synthesis of prostaglandins so pain and inflammation is less. Some NSAIDs inhibit one kind of COX, while others inhibit both types to varying degrees.  COX-1 inhibits the formation of thromboxane A2, which contributes to platelet aggregation.  Aspirin is almost exclusively a COX-1 inhibitor.  COX-1 also helps regulate kidney function, GI mucosa, and the hemostasis of blood.  You need COX-1 to maintain the production of gastric mucus and to protect the stomach wall.  This is why drugs like aspirin cause stomach ulcers. 

COX-2 is usually not found in normal tissues, except the brain, bones, kidneys, and the female reproductive organs, particularly the ovaries and uterus.  In injuries, COX-2 can be “turned on” so that it partakes in the inflammatory process.  It increases prostaglandin function (pain) in damaged tissues.  Instead of damaging GI tissue, it actually helps promote healing of the tissue. 

Exactly which NSAID to take depends on whether or not it works and on its side effect profile.  It is estimated that you should try an NSAID for about a week before deciding it is not going to work, except for piroxicam, which has a long half-life and should be tried for about 2 weeks.  Naproxen is believed to have the lowest side effect profile and is found in medications like Aleve®.  Ibuprofen and fenuprofen also have a relatively low side effect profile.  Some NSAIDs contribute to infertility and can cause harm to the fetus so should not be taken. 

Start with the lowest dose possible to make sure there are no allergies or toxicities and work up to higher, acceptable doses until symptoms are relieved.  Most NSAIDs relieve pain and inflammation to the same degree when taken in prescribed doses.  For things like period cramps (dysmenorrhea), the non-salicylate NSAIDs seem to work better than regular salicylate NSAIDs.  COX-2 inhibitors like celecoxib are indicated for dysmenorrhea specifically.  The dosing recommendations for pain are different from the dosage recommendations for inflammation.  The longer the half-life, the longer the pain relief you will experience.  It can take up to a month for full anti-inflammatory effects to begin to work. 

Some dosage adjustments are necessary for the elderly and for children.  This is because renal clearance of drugs varies with kidney function.  There are more drug-drug interactions and worsened GI symptoms in the elderly population.  Dosages should be reduced in those with either liver or kidney disease. 

There are a lot of side effects of NSAIDs.  These include GI effects, such as dyspepsia, stomach ulcers, nausea, vomiting and gastrointestinal bleeding.  Those that inhibit COX-1 cause more problems than those that inhibit COX-2.  Liver toxicity can happen, even with aspirin.  Kidney problems, including kidney failure have been noted when taking medications such as indomethacin, piroxicam, and ketorolac. Other side effects are related to the central nervous system and include headache, nightmares, dizziness, and confusion.  Ringing of the ears is possible with aspirin.  Aspirin can also cause an exacerbation of asthma and Reye’s syndrome in kids.

Drug to drug interactions are many with NSAIDs and it depends on which NSAID you take.  This is why it is important to talk to the pharmacist or doctor and to tell them all of the medications you are currently taking, including herbal preparations. 

Cost is another factor to consider.  Some NSAIDs are considerably cheaper than others and those that have generic equivalents tend to be cheaper if you use the generic kind of medication.  Costs vary from pharmacy to pharmacy, so it pays to do your homework.

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