Treating Acute Gout: Indomethacin and NSAID’s
Indomethacin is a non-steroidal anti-inflammatory drug (NSAID) used to treat acute painful attacks of gouty arthritis. It is one of the original NSAID’s in its class gaining U.S. Food and Drug Administration (FDA) approval in 1965. In gout it is used to treat an acute episode of gouty arthritis, it is not useful or indicated as a preventative.
Indocin is a common brand name for indomethacin. Drugs like Indocin have been used to treat various inflammatory conditions for over 100 years. It has only been the last 20-30 years that medical research has understood the mechanisms by with these drugs work. Ongoing study reveals additional information and insights into the action of NSAID’s and the inflammatory response. As science identifies the complex role inflammation plays in many conditions, the role of indomethacin expands. To understand how Indocin treats gout, understanding the inflammatory response is necessary.
Inflammation occurs when the human body detects a substance it considers “foreign.” Each individual has cellular markers, protein sites on the walls of each cell, that identify that cell as “self.” When circulating white blood cells of a certain type identify a substance without these identifying markings it sets up a series of events called innate immunity. This is the “first responder” to a foreign protein like the venom from a bee sting, a bacteria, or even blood. When red blood cells are inside blood vessels, the body identifies them as belonging. When blood escapes the blood vessel into tissue from injury, it is no longer viewed as normal and innate immunity stimulates an inflammatory reaction.
Ancient healers identified the characteristics of inflammation long ago and the attributes still remain.
- Rubor means redness. The blood vessels dilate in the area of inflammation and create a reddish discoloration around the site.
- Dolar mean pain. The inflammatory reaction produces various chemicals that stimulate pain receptors. This helps limit your motion and the spread of the offending substance.
- Calor is heat. The increased local metabolic activity and increased circulation generate local warmth.
- Tumor is swelling. Increased fluids and cellular debris cause local edema.
Think about a bee sting. The area almost immediately becomes red, swollen, painful and hot. This is a local inflammatory reaction or innate immunity.
Prostaglandins and Cyclooxygenase
Prostaglandins are chemical mediators in the body that serve several important functions. A major role of prostaglandins is in the inflammatory reaction. Recent study suggests that prostaglandins not only have a vital role in starting and organizing the inflammatory response, but also is responsible for turning off the body’s reaction to inflammation.
Prostaglandins are made in every cell in the body. Specifically in inflammation, they are released in response to cell injury and are responsible for initiating the inflammatory response. In general, they call out to other immune cells already in circulation by chemical messaging (chemotaxis) and direct them to the site of the injury. They also stimulate the body to start production of the many types of white blood cells required to respond to the cellular damage. Prostaglandins can be thought of as the “first responders” to injury or invasion (bacterial and viral infection for example.)
One of the direct local effects of prostaglandins includes vasodilation, meaning enlargement of the blood vessels, which increases circulation to the area. When the blood vessels are bigger, more blood can be delivered. This carries more white blood cells and proteins to heal the inflammation. Another function is the stimulation of pain mediators. This helps keep the area of inflammation at rest. These account for the classic findings of inflammation (redness, swelling, pain and heat.)
Cyclooxygenase (COX) is the enzyme that converts a substance called arachidonic acid into prostaglandin. This occurs within each cell, not in the blood stream. Two Cox enzymes have been isolated and their respective functions identified.
- Cox 1 is primarily involved in the stomach lining, maintaining a healthy environment in the presence of erosive stomach acids. It also has a vital role in the kidneys. Cox 1 is responsible to dilate the blood vessels in the kidney when more blood flow is required, for example to eliminate toxins or in response to dehydration. It also is necessary to produce healthy platelets for normal blood clotting.
- Cox 2 is the stimulus for prostaglandins involved in inflammation and innate immunity.
Not All NSAID’s are Equal
Many NSAID’s, particularly the older one’s including indomethacin, are non-selective COX inhibitors. This means that the effects of the drug decrease the action of both Cox 1 and Cox 2. Less COX means less prostaglandin. Less prostaglandin means less inflammation. In recent years selective COX 2 inhibitor NSAID’s have been developed, which only target the COX 2 enzymes. The difference can be important in patients with other medical conditions such as peptic ulcer disease, clotting abnormalities or heart disease.
Selective versus Nonselective
A partial list of NSAID’s by Cox inhibition includes:
Non-selective COX inhibitors (targeting both COX 1 and COX 2)
- Acetylsalicylic acid (Aspirin)
- Indomethacin (Indocin)
- Ibuprofen (Motrin, Advil, Nuprin)
- Naproxen Sodium (Aleve, Anaprox, Midol Extended Relief, Naprosyn)
- Ketorolac (Toradol, Sprix)
- Sulindac (Clinoril)
- Pioxicam (Feldene)
- Diflunisal (Dolobid)
Selective Cox 2 inhibitors
- Celecoxib (Celebrex)
- Meloxicam (Mobic)
- Valdecoxib (Bextra)
- Nabumetone (Relefen)
- Etodolac (Lodine)
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