Cyclosporine is a drug obtained from a type of soil fungus found in Norway called Tolypocladium inflatum. The drug is valuable in organ transplants because it suppresses the action of certain cells in the body's immune (disease-fighting) system that can reject the transplanted organ. While preventing attacks of these cells, called T cells (or T-helper cells), cyclosporine lets the bulk of the body's immune system function normally and fight general infection.
Cyclosporine is a relatively new drug. It was approved by the U.S. Food and Drug Administration in 1983 for use in all transplant patients. Before the use of cyclosporine, live organs could be transplanted from one body to another, but the drugs necessary to prevent rejection of the foreign tissue weakened the patient's entire immune system. Frequently patients could not survive the severe infections that followed transplants, and mortality (death) rates for transplant patients were discouragingly high. The discovery of cyclosporine brought about a major shift in the success of transplantation.
Jean-Francois Borel (1934-), a microbiologist working for Sandoz Laboratories in Switzerland, discovered cyclosporine in 1969 when he was vacationing in Norway. Sandoz employees were encouraged to gather samples of naturally occurring organisms for analysis in the laboratory. When Borel visited Hardanger Vidda, a desolate highland plateau in southern Norway, he collected some soil samples and brought them back to Sandoz for testing.
Sandoz Laboratories was involved primarily in antibiotics research, and the purpose of their first series of tests on cyclosporine was to determine the substance's potential as an antibiotic. The tests yielded little of interest as far as antibiotics were concerned, but did show that cyclosporine had distinct immunosuppressive capabilities. Since his doctoral studies involved immunogenetics (the study of how the immune system works), Borel decided that he wanted to learn more about cyclosporine.
Borel ran a second series of tests and found that cyclosporine inhibits the activity of lymphocytes (white blood cells), the part of the immune system that starts the process of detecting and attacking foreign invaders. Lymphocytes aid in the formation of cytotoxic (toxic to cells) T cells. These cells, along with blood cells called monocytes and macrophages, are thought to be responsible for the rejection of transplanted organs. Cyclosporine does not actually destroy the T cells, but fends them off. It acts at an early stage in the life cycle of the T cell, inhibiting its action by blocking the intercellular message carried by a cellular compound called interleukin-2.
A Disappointing Setback
It looked as if Borel had discovered a superior drug for transplantation, but his employer was not sufficiently impressed by the findings he reported in 1972. The estimated costs for production and testing of the drug were too high, and organ transplantation was just getting started. The potential demand for cyclosporine was questionable. Sandoz was unwilling to put the necessary money and energy behind the drug for further exploration.
Two immunologists recognized the importance of Borel's discovery, however, when the researcher presented his results to the British Society of Immunologists in 1976. David White and Sir Roy Calne asked Borel for samples of cyclosporine and began their own clinical studies using organ transplantation in rats. The results were remarkable: rejection was almost nonexistent, and the survival rate was far better than for other immunosuppressants. In mid-1977, White and Calne informed Borel of their findings and requested more samples of cyclosporine to continue their clinical trials, this time on dogs. Borel, hoping to revive Sandoz's interest in cyclosporine, asked White and Calne to present their findings to Sandoz. The pharmaceutical company agreed that the drug looked much more promising now that there was evidence of its effectiveness.
The success of cyclosporine suffered a setback in 1979 when further studies showed it to be nephrotoxic (poisonous to the kidneys) and to cause lymphomas (tumors). These side effects proved to be the result of high doses of the drug. The practice at the time was to administer as much cyclosporine as the body could handle, short of a toxic level. Research later showed it should be given in small amounts, just enough cyclosporine to prevent rejection of a transplanted organ. With the decreased dosage, the lymphoma was eliminated and nephrotoxicity was reduced.
Later research by Thomas Starzl in Colorado indicated that cyclosporine worked most effectively when administered with steroids. In 1983 the Food and Drug Administration approved cyclosporine for use in all transplant patients, but said it must be given only in conjunction with steroids. Cyclosporine must be taken indefinitely by persons who have received organ transplants, however, and the possibility of irreversible kidney failure remains a serious concern.
Cyclosporine is not a perfect drug, but it is the most potent (strong) and specific immunosuppressant available for organ transplant patients. It is effective in treating infections after the surgery, and it is associated with a lower mortality rate among transplant patients. It is commonly used in kidney, heart and lung, liver and pancreas, and bone marrow transplants. Cyclosporine is also used to treat viral and fungal infections and immune disorders, to promote healing of wounds, and in certain kinds of tissue grafts. The drug is also used in treating certain autoimmune diseases such as myasthenia gravis and is being tested for use in treating inflammatory bowel disease.
"Cyclosporine." Medical Discoveries. . Encyclopedia.com. (February 19, 2018). http://www.encyclopedia.com/medicine/medical-journals/cyclosporine
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Cylosporine is an immunosuppressant drug used to prevent rejection of kidney, liver, and heart transplants, to prevent graft-versus-host disease in patients receiving allogeneic bone marrow transplants, and for severe autoimmune diseases that are resistant to corticosteroids and other therapy. Cyclosporine, also spelled as cyclosporin and ciclosporin, takes several brand names in the United States, including Neoral, Sandimmun, Sandimmune, and Sang Cya. It is also known in slight variant forms, such as cyclosporin A, CsA, and CyA. The Neoral and Sang Cya brand name products are interchangeable, but the Sandimmune brand name product can not be used interchangeably for those other two products.
Cyclosporine is best known as a drug used to prevent the rejection of organ transplants and bone grafts.
Discovered in 1972, cyclosporine was first isolated from a fungus. It suppresses (prevents the activity of) the cells in the lymphatic system, known as T cells, that would otherwise mount an immune response . This suppression makes cyclosporine useful in conjunction with organ transplants. (In a transplant, the patient receiving a donated organ can react to the organ as though it were a foreign substance, rejecting it.) Cyclosporine is also used to treat severe rheumatoid arthritis, and is being used investigationally as a drug that may help to temper multidrug resistance in cancer patients.
The drug is available in several forms, including an intravenous (I.V.) solution, an oral solution, and an oral capsule. Cyclosporine is broken down in the liver.
The dosage varies, depending on the reason for use and the patient, and the dosage is also often adjusted by the physician. The dosage is based on the patient's ideal body weight, and the oral dose is approximately three times higher than the intravenous dose. I.V. use is only reserved for patients who cannot take the oral dose, and it is recommended that patients who can be switched to the oral form be switched as soon as possible.
The usual initial oral dose is 14-18 mg/kg per day, beginning four-twelve hours before organ transplantation. After the transplantation, the dose is decreased, and then usually tapered to 3-10 mg/kg per day.
Cyclosporine can cause infection and possibly lymphoma , and is toxic to the kidneys. The use of this drug along with other drugs that are toxic to the kidneys must be closely monitored. It should be ingested and swallowed in its capsule without breaking the capsule. The liquid solution should only be mixed in a glass container. Pregnant or nursing women should not take this drug, and patients taking this drug will be more susceptible to infection. Therefore, crowds of people should be avoided, and no live vaccines should be adminstered to the patient without consulting the patient's doctor. Patients should inform their doctor of any hypersensitivities or drug allergies they have before taking this drug. (Cyclosporine in both liquid and capsule form has some castor oil components in it, which could cause an allergic reaction for some.) Some allergic reactions to the I. V. solution may be severe. This drug has not been specifically studied for use with the elderly.
More than 10% of patients taking this drug experience the following:
- high blood pressure
- unusual hair growth
- kidney toxicity
- thickening of the gums
Other, less common side effects include: seizures, headache, acne, abdominal pain, nausea and vomiting , leg cramps, and some endocrine/metabolic conditions known as hypomagnesia, hypokalemia, hyperkalemia, and hyperlipidemia.
Cyclosporine interacts with a long list of other drugs. A physician should be informed about each and every drug a person eligible for treatment with cyclosporine is taking. Drugs that may make cyclosporine less effective include: carbamazepine , phenobarbital, phenytoin , and others. Drugs that may increase cyclopsporine's toxicity include: acyclovir, amphotericin B, corticosteroids, erythromycin, certain antibiotics , and some antifungals including fluconazole, itraconazole, and ketaconazole. Cyclosporine should not be taken with grapefruit or related juices because the combination can make it more toxic. Vaccinations should not be given while a person is taking cyclosporine.
Diane M. Calabrese
—A tube that is inserted directly into a vein to carry medicine directly to the bloodstream, bypassing the stomach and other digestive organs that might alter the medicine.
—The system that collects and returns fluid in tissues to the blood vessels and produces defensive agents for fighting infection and invasion by foreign bodies.
—Metric measure that equals 2.2 pounds.
—One-thousandth of a gram. A gram is the metric measure that equals about 0.035 ounces.
"Cyclosporine." Gale Encyclopedia of Cancer. . Encyclopedia.com. (February 19, 2018). http://www.encyclopedia.com/medicine/encyclopedias-almanacs-transcripts-and-maps/cyclosporine
"Cyclosporine." Gale Encyclopedia of Cancer. . Retrieved February 19, 2018 from Encyclopedia.com: http://www.encyclopedia.com/medicine/encyclopedias-almanacs-transcripts-and-maps/cyclosporine
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"ciclosporin." A Dictionary of Nursing. . Encyclopedia.com. (February 19, 2018). http://www.encyclopedia.com/caregiving/dictionaries-thesauruses-pictures-and-press-releases/ciclosporin
"ciclosporin." A Dictionary of Nursing. . Retrieved February 19, 2018 from Encyclopedia.com: http://www.encyclopedia.com/caregiving/dictionaries-thesauruses-pictures-and-press-releases/ciclosporin