Treating Gout: Colchicine
History
Colchicine for gout has been used to treat acute attacks for many years. Colchicine is derived from a plant called Autumn Crocus, and as early as 3,500 years ago the healing effects of Autumn Crocus on pain and swelling were written about in Egyptian medical scrolls. Numerous references have been made throughout history about the use of this plants extracts in the treatment of gout and other inflammatory conditions. These writings also attest to the immense suffering gout has inflicted on people all over the world throughout history.
FDA History
The use of colchicine for gout was not approved by the FDA, but in combination with probenecid it was approved for treatment of hyperuricemia, or high blood levels of uric acid. In 2009, the FDA awarded a major drug company exclusive marketing for three years and an indication for the monotherapy in gout and two other conditions. One of the conditions of this “FDA deal” was the company’s agreement to spend 100 million dollars in research via 17 designated studies into the drug . . . and 45 million of those dollars went to the FDA as the application fee! Consequently, in 2010 the FDA pulled all existing stock of the old colchicine off shelves. The price of a colchicine tablet increased from about $0.09 to more than $4.50 a dose. Do you smell a rotten fish? I do.
Inflammatory Response
In order to understand how colchicine for gout works, we must first understand the inflammatory response to uric acid crystals in joint spaces. An inflammatory reaction is the body’s first response to injury or infection. Called “innate immunity” it is a general reaction the body makes to anything it considers “foreign.” This can be many things such as venom from a bee sting, a bacteria growing where it shouldn’t or blood in the wrong place.
On every normal cell within the body there are proteins on the cell surface that let the body’s defenses know that the cell is “self.” Certain white blood cells float around just looking for cells without this protein marker, which they then identify as “foreign.” When they find such foreign cells, they are able to call in many other white blood cells to respond. They also stimulate the body to crank up production of the first line of defense to “neutralize” the “foreign” cells.
The classic inflammatory response creates typical symptoms, no matter where in the body or to what the response is started. Known since ancient times, the inflammatory reaction is still identified by Latin names. These four findings are:
- Rubar = redness. A red discoloration in the area of the reaction develops. This is partly from dilated blood vessels delivering white blood cells into the area and also to help carry away cellular debris.
- Dolar = pain. The reaction itself stimulates production of many other chemicals including substance P and other pain generating compounds.
- Calor = heat. The increased biochemical activity generates increased temperature.
- Tumor = swelling. The local area around the inflammatory reaction becomes infiltrated with fluids, cells and becomes swollen.
Think about the immediate reaction of the skin to a bee sting. The area around the sting becomes red, swollen, tender and hot. These are the inflammatory changes caused by the initial innate immune response. The same thing happens in a joint when the joint capsule and joint surfaces are injured by uric acid crystals.
Another example is this: When red blood cells are circulating inside blood vessels, the white blood cells identify them as “self.” However, when red blood cells find their way outside of blood vessels, they are viewed as “foreign” and the body mounts an inflammatory reaction.
Uric acid crystals injure the joint capsule lining and red blood cells are released starting the inflammatory reaction. As the joint becomes swollen (tumor), and red (rubor), and painful (dolar) and hot (calor) it puts stress on the cartilage lining that makes up the joint space, which then becomes injured. The inflammatory reaction is then initiated to the cartilage of the joint itself as well as the fluid filled capsule. Then you have a full-fledged acute gout attack. White blood cells flood the area in an attempt to “neutralize” the identified “foreign” proteins.
Colchicine
Colchicine for gout does nothing for the condition itself. It works on stopping the body from making the white blood cells that are the body’s response to the gout. By decreasing the production of the white blood cells, it limits the inflammatory response and subsequently decreases the pain, swelling, redness and heat.
Don’t Mess With Mother Nature
In order to make new cells of any kind (except reproductive cells) in the body, the process of splitting one cell into two requires duplicating the genetic material (DNA). During cell division, the dividing cell makes a structure called microtubules that attach to the DNA and pull half into one cell and half into the other. After the separation is complete, these microtubules disintegrate and the molecules left are recycled for the next cell division.
During cell reproduction colchicine binds to the protein tubulin and prevents microtubules from being formed in the early white blood cell responders. No microtubules means no cell division. No cell division means less inflammatory response. Less inflammatory response means decreased pain, swelling, heat and redness.
In addition to that, colchicine has been shown to have a “uricosuric effect”, which means it increases elimination of uric acid via urine. This is not how the drug helps an acute attack, but it may explain its recent approval as a preventative gout medicine. There are other agents available that promote uric acid excretion without interfering with the genetic process of cell reproduction. Those would be better choices!
Side Effects of Colchicine
One of the major problems with the use of colchicine for gout is that it has what is called a narrowed therapeutic index. This means that the amount of colchicine required to provide relief is very close to the toxic dose. The major side effect is gastrointestinal distress, more specifically diarrhea. Often the recommended usage instructions will say “take every two hours until pain is improved or diarrhea starts.” More often than not the diarrhea wins! Additional common complaints are abdominal pain, nausea and vomiting.
Other less common side effects can include bleeding in the stool or urine, headache, hives, numbness in the hands or feet, pain, fatigue, weakness, or sores in the mouth.
Other Indications for Colchicine
Along with the approval of colchicine for gout, it has also been approved for the treatment of:
- Pericarditis – a potentially life threatening infection or inflammation of the heart lining
- Familial Mediterranean Fever – an inherited condition that causes a lifetime of pain and disability
- Behcet’s Disease – a potentially fatal and painful disorder, it is being researched for a role in certain cancer therapies.. . .
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