Sulfasalazine
Encyclopedia
Sulfasalazine was developed over 70 years ago specifically to treat rheumatoid arthritis
. It was believed at the time that bacterial infections were the cause of rheumatoid arthritis. Sulfasalazine is a sulfa drug, (a derivative of mesalazine
) and is formed by combining sulfapyridine and salicylate with an azo bond. It may be abbreviated SSZ.
Sulfasalazine is used in the treatment of inflammatory bowel disease, including ulcerative colitis
and Crohn's disease
. It is also indicated for use in rheumatoid arthritis
and used in other types of inflammatory arthritis (e.g. psoriatic arthritis
) where it has a beneficial affect. It is often well tolerated compared to other DMARDS.
In recent British research involving animal studies, and more recently, human trials for the treatment of chronic alcoholics, sulfasalazine has been found to reverse the scarring associated with cirrhosis of the liver. Cells called myofibroblasts, which contribute to scar tissue in a diseased liver, also appear to secrete proteins that prevent the breakdown of the scar tissue. Sulfasalazine appears to retard this secretion.
A study at University of Newcastle
found that the drug may also act to aid the healing of cirrhosis of the liver.
It is usually not given to children under 2 years of age.
The use of sulfasalazine in inflammatory bowel disease has declined due mainly to the fact that it yields the metabolite sulfapyridine
which gives rise to side-effects such as agranulocytosis
and hypospermia
. However, the other metabolite of sulfasalazine, 5-aminosalicylic acid (5-ASA) is attributed to the drug's therapeutic effect. Therefore, 5-ASA and other derivatives of 5-ASA, are now usually preferred and given alone (as mesalazine
), despite their increased cost, due to their more favourable side-effect profile.
Sulfasalazine has also been used successfully to treat cases of idiopathic urticaria
that do not respond to antihistamines.
), sulfasalazine has no immunosuppressant
action.
Because sulfasalazine and its metabolite 5-ASA are poorly absorbed into the bloodstream, it is surprising that the drug is effective against symptoms outside of the intestine. One possible explanation is that, given that ulcerative colitis produces arthritic symptoms, the arthritic symptoms are actually a product of unrecognized ulcerative colitis, which is effectively treated with sulfazalazine.
The other metabolite, sulfapyridine, is absorbed into the blood, and is believed to be the source of the side-effects discussed below. It is possible that the sulfapyridine is responsible for some of the anti-arthritic effects of sulfasalazine.
In rare cases, Sulfasalazine can cause severe depression
in young males. It can also cause temporary infertility
.
Sulfsalazine metabolizes to sulfapyridine. Serum levels should be monitored every three months, and more frequently at the outset. Serum levels above 50 μg/l are associated with side effects.
Immune thrombocytopenia
has been reported.
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
. It was believed at the time that bacterial infections were the cause of rheumatoid arthritis. Sulfasalazine is a sulfa drug, (a derivative of mesalazine
Mesalazine
Mesalazine , also known as Mesalamine or 5-aminosalicylic acid , is an anti-inflammatory drug used to treat inflammation of the digestive tract ulcerative colitis and mild-to-moderate Crohn's disease...
) and is formed by combining sulfapyridine and salicylate with an azo bond. It may be abbreviated SSZ.
Indications
- See also Disease-modifying antirheumatic drugDisease-modifying antirheumatic drugDisease-modifying antirheumatic drugs is a category of otherwise unrelated drugs defined by their use in rheumatoid arthritis to slow down disease progression...
s for its role in rheumatoid arthritisRheumatoid arthritisRheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
Sulfasalazine is used in the treatment of inflammatory bowel disease, including ulcerative colitis
Ulcerative colitis
Ulcerative colitis is a form of inflammatory bowel disease . Ulcerative colitis is a form of colitis, a disease of the colon , that includes characteristic ulcers, or open sores. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset...
and Crohn's disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...
. It is also indicated for use in rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
and used in other types of inflammatory arthritis (e.g. psoriatic arthritis
Psoriatic arthritis
Psoriatic arthritis is a type of inflammatory arthritis that, according to the National Psoriasis Foundation, will develop in up to 30 percent of people who have the chronic skin condition psoriasis...
) where it has a beneficial affect. It is often well tolerated compared to other DMARDS.
In recent British research involving animal studies, and more recently, human trials for the treatment of chronic alcoholics, sulfasalazine has been found to reverse the scarring associated with cirrhosis of the liver. Cells called myofibroblasts, which contribute to scar tissue in a diseased liver, also appear to secrete proteins that prevent the breakdown of the scar tissue. Sulfasalazine appears to retard this secretion.
A study at University of Newcastle
University of Newcastle upon Tyne
Newcastle University is a major research-intensive university located in Newcastle upon Tyne in the north-east of England. It was established as a School of Medicine and Surgery in 1834 and became the University of Newcastle upon Tyne by an Act of Parliament in August 1963. Newcastle University is...
found that the drug may also act to aid the healing of cirrhosis of the liver.
It is usually not given to children under 2 years of age.
The use of sulfasalazine in inflammatory bowel disease has declined due mainly to the fact that it yields the metabolite sulfapyridine
Sulfapyridine
Sulfapyridine, original UK spelling Sulphapyridine, is a sulfonamide antibacterial. At one time it was commonly referred to as M&B....
which gives rise to side-effects such as agranulocytosis
Agranulocytosis
Granulopenia, also known as Agranulosis or Agranulocytosis, is an acute condition involving a severe and dangerous leukopenia , most commonly of neutrophils causing a neutropenia in the circulating blood. It represents a severe lack of one major class of infection-fighting white blood cells...
and hypospermia
Hypospermia
Hypospermia is the medical term when a man has an unusually low ejaculate volume, it is the logical opposite of Hyperspermia. It should not be confused with Oligospermia, which means low sperm count....
. However, the other metabolite of sulfasalazine, 5-aminosalicylic acid (5-ASA) is attributed to the drug's therapeutic effect. Therefore, 5-ASA and other derivatives of 5-ASA, are now usually preferred and given alone (as mesalazine
Mesalazine
Mesalazine , also known as Mesalamine or 5-aminosalicylic acid , is an anti-inflammatory drug used to treat inflammation of the digestive tract ulcerative colitis and mild-to-moderate Crohn's disease...
), despite their increased cost, due to their more favourable side-effect profile.
Sulfasalazine has also been used successfully to treat cases of idiopathic urticaria
Urticaria
Urticaria is a kind of skin rash notable for pale red, raised, itchy bumps. Hives is frequently caused by allergic reactions; however, there are many non-allergic causes...
that do not respond to antihistamines.
Mode of action
Sulfasalazine, and its metabolite 5-ASA, are poorly absorbed from the gut. Its main mode of action is therefore believed to be inside the intestine.Bowel disease
In Crohn's disease and ulcerative colitis, it is thought to be an antinflammatory drug that is essentially providing topical relief inside the intestine. It does this via a number of mechanisms such as reducing the synthesis of inflammatory mediators known as eicosanoids and inflammatory cytokines. However, unlike glucocorticoids (another class of drug used in the treatment in inflammatory bowel diseaseInflammatory bowel disease
In medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
), sulfasalazine has no immunosuppressant
Immunosuppressant
An immunosuppressant is any substance that performs immunosuppression of the immune system. They may be either exogenous, as immunosuppressive drugs, or endogenous, as ,e. g., testosterone...
action.
Arthritis
When treatment for arthritis is successful, pain, joint swelling and stiffness will be reduced and this may slow down or stop the development of joint damage. The precise reasons why sulfasalazine are effective in various forms of arthritis is not clearly understood.Because sulfasalazine and its metabolite 5-ASA are poorly absorbed into the bloodstream, it is surprising that the drug is effective against symptoms outside of the intestine. One possible explanation is that, given that ulcerative colitis produces arthritic symptoms, the arthritic symptoms are actually a product of unrecognized ulcerative colitis, which is effectively treated with sulfazalazine.
The other metabolite, sulfapyridine, is absorbed into the blood, and is believed to be the source of the side-effects discussed below. It is possible that the sulfapyridine is responsible for some of the anti-arthritic effects of sulfasalazine.
Side effects
Refer to external links for a full listing of known side effects.In rare cases, Sulfasalazine can cause severe depression
Depression (mood)
Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...
in young males. It can also cause temporary infertility
Infertility
Infertility primarily refers to the biological inability of a person to contribute to conception. Infertility may also refer to the state of a woman who is unable to carry a pregnancy to full term...
.
Sulfsalazine metabolizes to sulfapyridine. Serum levels should be monitored every three months, and more frequently at the outset. Serum levels above 50 μg/l are associated with side effects.
Immune thrombocytopenia
Thrombocytopenia
Thrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...
has been reported.