Prescription NSAIDs in Pain Management

drugs

NSAIDs are nonsteroidal anti-inflammatory drugs. Non-prescription NSAIDs include ibuprofen and naproxen. Even aspirin and willow bark are considered NSAIDs. People have used them since the early 1900s (willow bark has 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, a more recent class of medications, used by prescription as nonsteroidal anti-inflammatory agents. Because they are new, the long-term implications of using these types of drugs have not been studied, and this is being studied. 

The Many Uses of NSAIDs

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

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 injury site and leakage of fluid and inflammatory molecules around the area. 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 creates a scar and regenerates healthy tissue. 

Acetaminophen

Acetaminophen is a good drug for fever but is not considered 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 for those who cannot tolerate NSAIDs. Because it does not affect inflammation, it should not be used when a significant amount of inflammation is associated with pain. Instead of acting as an anti-inflammatory, acetaminophen, marketed as Tylenol®, serves on the fever centers of the hypothalamus. It increases sweating, promoting a decrease in body temperature. Its effectiveness in controlling pain isn’t understood very well. 

Aspirin

Aspirin and other salicylates metabolize in the body into salicylic acid. Aspirin is the only NSAID that acts on platelets, while all NSAIDs act on pain and inflammation. Salicylates go to the site of inflammation to work, blocking prostaglandin synthesis, which causes pain and inflammation. 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, directly impacting the hypothalamic fever centers and decreasing fever. It also causes dilatation of the blood vessels of the body, causing a decrease in body temperature. 

Other NSAIDs act differently from aspirin but do the same things (except inhibit platelet aggregation). They can be even more potent 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, ibuprofen, and prescription drugs ketoprofen, oxaprozin, and fenoprofen. COX-2 inhibitors are another standard 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 it cannot be taken by people with sulfonamide allergies. Interestingly, those who are allergic to aspirin must avoid taking all types of NSAIDs, even those that are not salicylates. 

Types of COX

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 are 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 blood hemostasis. You need COX-1 to maintain gastric mucus production and 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” to participate in the inflammatory process. It increases prostaglandin function (pain) in damaged tissues. Instead of damaging GI tissue, it actually helps promote the healing of the tissue. 

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

Dosage

Start with the lowest dose possible to ensure no allergies or toxicities, and work up to higher, good doses until symptoms are relieved. Most NSAIDs reduce pain and inflammation to the same degree when taken in prescribed amounts. 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 work. 

Some dosage adjustments are necessary for the elderly and for children. This is because renal clearance of drugs varies with kidney function, and 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. 

Side Effects

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, including 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.

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

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

Photo by Myriam Zilles on Unsplash

[cs 1209]

Client Reviews
★★★★★
"Me and my wife; had a car accident. We were amazed how easy, professional, friendly attorney Ed Smith is along with his staff. Everybody is amazing. Thank you so much, we are very impressed!" Alex & Dinah M.
★★★★★
"Ed Smith and his office team took on a difficult personal injury case on my behalf and for the passenger in my car. Ed is a top- notch attorney. His staff couldn't have been more helpful and kind. No need to look elsewhere. I give Ed Smith my highest recommendation." Beverly
★★★★★
"Ed and Robert have been taking great care of my husband and I for the past 5+ years. They are always there when you have a problem and a quick resolution! Even when the issues have nothing to do with them. They are willing to help ease the pain off your shoulders. They are as good as it gets! Thank you again for everything." Annie T.
★★★★★
"Very professional. Great team, staff and service all around. Mr Smith was very honest, straight forward with his advice. He gives the word "attorney" an honest reputation. I will seek his council anytime, and would recommend him at the drop of a dime." Jeremy M.
★★★★★
"I would highly recommend Ed Smith to any friends or family in need of a personal injury attorney. Ed, and his staff, are very caring on top of being very experienced in this field. The staff always keeps you informed of the status of your case and they are always easy to reach by phone." Shannon D.
★★★★★
"Edward Smith law offices provide competent, thorough, and personable help for victims of personal injury. When you first meet the staff you know you contacted the right office. This law office treats clients like people. I recommend this office to anyone seeking representation regarding personal injury." David M.