In nature, there are substances that can suppress cellular and humoral immunity in the animal organism, carried out by T-lymphocytes. This made it possible to successfully carry out organ transplants and treat diseases associated with impaired immune systems. One of these natural compounds is cyclosporin.
Description
The discovery of this substance is associated with the study of fungal strains of Tolypocladium inflatum and Cylindrocarpon lucidum. The biologically active substances synthesized by them, such as cyclosporin A and C, exhibit immunological activity against lymphocytic blood cells. This feature was first discovered in 1972 by scientists from the Sandoz laboratory in Switzerland. According to the chemical structure, cyclosporin is a neutral lipophilic cyclic endecapeptide with a pronounced specific immunosuppressive effect.
Preparations based on it have a selective effect on T-lymphocytes, suppress cellular and humoral immunity. Cyclosporin in the blood inhibits the production of lymphokines, which reduces lymphocytic activity, but does not affect the process of hematopoiesis and the work of phagocytes, which indicates the selective action of this compound in the body.
Dosage Forms
Be sure to be included with the medication containing cyclosporine, instructions for use. Among other things, it includes information on the form of release of the drug. Preparations with this substance are released in the form of:
- soft capsules with a dosage of 25, 50 and 100 milligrams;
- alcohol solution for oral administration with 100 milligrams of cyclosporine in one milliliter of solution;
- an oil solution for oral administration with 100 milligrams of cyclosporine in one milliliter of solution;
- concentrate for the manufacture of a solution for infusion with 50 and 650 milligrams of cyclosporine in one milliliter;
- eye drops with 500 micrograms of cyclosporine in one milliliter.
Depending on the dosage form, the application will be different: for internal use, for injection, for topical use.
It is believed that according to the absorption rate of the active component, the accumulation time of the highest concentration in the blood, the capsules and the internal solution are considered equivalent.
The drug "Cyclosporine": analogues
In the pharmaceutical market there are a number of drugs produced in the same pharmaceutical form and having almost the same effect. The active substance in them is cyclosporine. Instructions for use synonymous with immunosuppressants are considered interchangeable drugs to suppress immune responses.
Among the encapsulated medicines in a soft gelatin shell and liquid solutions, the original product is Sandimmun Neoral, manufactured by the Swiss pharmaceutical company Novartis. The remaining drugs are considered to be reproduced in the likeness of the first created composition with the substance cyclosporine. Analogs, such as Cyclosporin Hexal, Ecoral, Cyclopren, Cyclosporin A, are available in capsule or solution for internal use or injection.
Their main purpose is to reduce rejection during transplantation of internal organs or bone marrow. They also treat autoimmune diseases, as evidenced by the instructions for use attached to the Cyclosporin preparation. Analogs have the same characteristics and indications for use.
The mechanism of action of the drug "Cyclosporin A"
The basis of the action of all immunosuppressive drugs is the selective effect on T-lymphocytes. The drug “Cyclosporin A” is no exception. The instruction covers in detail the basic pharmacodynamic mechanisms of action of the active component, which connects with receptor formations inside the cells. There is a decrease in the production of interleukins and interferon, and the expression of IL-2 receptors is reduced.
The medicine “Cyclosporin A” reduces the production of antibodies directed at the body’s own cells and tissues, which they consider to be foreign and destroy. This feature allows to reduce immunological disorders and reduce the activity of autoimmune diseases.
Great efficacy of "Cyclosporin A" in relation to allograft. The reason for rejection of transplanted tissues and organs is the activation of immunity created by T cells. It is they who actively begin to be produced under the action of transplantation antigens and act on the graft cells, leading to their death.
The action of the immunosuppressant leads to the blocking of the T-cell link and the inhibition of T-lymphocytes that occur during immune responses. Therefore, the effectiveness of the drug “Cyclosporin A” (instructions indicate this) is achieved only after the suppression of transplant antigens. By destroying the relationship between the antigen and the antibody, necrosis of cells of transplanted organs is prevented.
What is it used for?
Indications for use of the drug "Cyclosporin" instructions for use are divided into two categories.
The first includes transplantation or transplantation of donor tissues and organs. The medication is used to prevent rejection of a planted organ or tissue. Typically, skin, heart, bone marrow, lungs, liver, kidney, pancreas are used as transplants. Perhaps the use of the drug to eliminate rejection when using other immunosuppressants. The second category includes severe autoimmune diseases. Also, the drug is prescribed for the low effectiveness of other drugs.
What diseases are treated with Cyclosporin? The instructions for use include, among the indications, acute forms of atopic dermatitis and neurodermatitis, manifestations of psoriasis, rheumatoid arthritis, in which small joints are affected and inflamed. It can be used for uveitis in the middle and posterior parts of the eye, when the choroid and retina become inflamed, and the nephrotic syndrome is hormone-dependent and hormone-resistant in nature.
Admission Rules
Treatment with the drug is recommended only under medical supervision in a hospital setting. Usually, internal use or intravenous drip is used, although oral administration of the solution or capsules is preferred.
The dishes used to prepare the solution for intravenous injection should be made of glass, not polyvinyl chloride, so that there is no reaction with castor oil.
A physiological 0.9 percent sodium chloride solution or 5 percent glucose solution is used to dilute the concentrate. Dilution is practiced in proportions from 1:20 to 1: 100, depending on the purpose. The drug is administered slowly, from two to six hours.
Before transplanting organs or tissues, a cyclosporin solution is pre-administered in about four to ten hours. To prevent the manifestation of allergies, antiallergic treatment and other immunosuppressants are prescribed in parallel. After two weeks of intravenous administration of the drug, they switch to oral administration. The daily dose prescribed by the doctor is taken twice in twelve hours.
Capsules are drunk whole, without opening the shell, washed down with water. The drug in liquid form is diluted with oral water before drinking in a glass beaker. The instructions describe in detail how to unpack the package and how to collect the solution with a graduated syringe from a glass bottle in order to correctly select the right amount of the drug. After using the solution, rinse the container with water and drink this liquid so that there is no dose loss.
The concomitant use of medication and grapefruit juice is contraindicated, which reduces the effect of the drug, and vaccination with live and weakened serums against rubella, polio, measles, and mumps is prohibited during treatment.
Dosage
When transplanting adults, they start taking it with a daily dose of 10-14 milligrams per kilogram of weight. After seven to fourteen days of treatment, the concentration of cyclosporin in the blood is measured. It is affected by the rate of absorption and transformation in the body. This indicator is important to control in order to prevent side effects and eliminate negative interactions with other medicines. After that, the daily dose of this drug is reduced to 3-6 milligrams per kilogram of weight, it is divided into two uses. The therapeutic content of cyclosporine in plasma in this case ranges from 110 to 410 nanograms per milliliter.
After a kidney transplant, taking a medication in a dose of less than three to four mg per kilogram of weight can provoke organ rejection.
A bone marrow transplant requires the use of a combination of cyclosporin and methotrexate. A couple of days before the start of transplantation, the patient begins to be administered intravenously from 2.5 to 5 milligrams of substance per kilogram of weight per day.
After switching to treatment with capsules, they start with a daily dose of 12.5 milligrams per kilogram of weight, which is taken twice. Therapy with such an amount of the drug lasts from three to six months. Gradually, you need to reduce the dosage until the end of the treatment period.
To eliminate the acute condition, first use a daily dosage of the drug from 12.5 to 15 milligrams per kilogram of weight (take in two approaches). Fifty days later, the dosage is reduced by five percent per week, and after five months, the drug is stopped. In case of a repeated reaction, additional treatment with the Cyclosporin medication is carried out. Instructions for use, reviews contain information on the survival rate of transplanted organs (heart, liver). According to statistics, in one year it reaches eighty percent.
The treatment of autoimmune diseases requires a special approach to the choice of dose for each disease.
By taking the drug “Cyclosporin”, the instructions for use recommend the treatment of severe uveitis. You need to start with a daily dose of 5-10 milligrams per kilogram of weight and adhere to it until the inflammatory process decreases and the visual function normalizes. The course of treatment is from three to sixteen months. In severe lesions, a combination with prednisone in a dose of 200 to 600 micrograms per kilogram of patient weight is possible.
In severe psoriasis, the daily dose is 2.5 milligrams per kilogram of weight, the reception is carried out in two approaches. The dosage is increased by 1 milligram per kilogram of weight, but not more than 5 milligrams per kilogram, if thirty days after the start of therapy there are no improvements. Reception is canceled after six weeks if treatment is ineffective.
Nephrotic syndrome with normal renal function in adults is treated using a dosage of up to 6 milligrams per kilogram of weight, in children up to 5 milligrams per kilogram of weight. If kidney function is impaired, the dosage is not more than 2.5 milligrams per kilogram of weight.
During treatment with the drug, the content of cyclosporin in the blood plasma is monitored. For therapeutic efficacy, its concentration in the blood is required in the amount of 60-160 nanograms per milliliter.
During the first three months, it is mandatory to control the level of creatinine in the blood serum, since an increase in this indicator may signal the beginning of rejection of the transplanted organ or damage to the kidneys. For people whose kidneys work fine, an analysis is carried out every fourteen days, if there are abnormalities, creatinine is measured every seven days. With a concentration of this indicator above 200 μmol per liter for adults and above 140 μmol per liter for children, the drug is discontinued.
Due to the possible toxic effects of the drug, periodic monitoring of the content of bilirubin, urea, amylase, magnesium and potassium ions in the blood is carried out, and the activity of liver enzymes is determined.
During the first one and a half months, severe rheumatoid arthritis is treated with Cyclosporin in a daily dosage of 2.5 milligrams per kilogram of weight; with subsequent therapy, the daily dose should not exceed 4 milligrams per kilogram of weight. With poor tolerance of the medication, you can reduce its amount to the minimum effective dose. It is possible to combine Cyclosporin with a small amount of glucocorticosteroids or non-steroidal anti-inflammatory drugs.
Severe forms of atopic dermatitis are treated by taking a dose of 2.5 milligrams per kilogram of weight per day. In the absence of effect, after fourteen days, the maximum daily dosage is prescribed - 5 milligrams per kilogram of weight. If improvement is observed, a gradual decrease in the dose of the drug is recommended.
How is cyclosporine used for eyes? Eye drops
Immunosuppressive drugs have also been used in ophthalmology for the treatment of dry keratoconjunctivitis. For these purposes, cyclosporine is also used. Eye drops with its content (0.05 percent) are produced under the trade name Restasis.
This tool belongs to the group of medicines used to protect and moisturize the cornea of the eye. The drug is produced in single-dose vials of 0.4 milligrams with a content of 500 μg of active substance in one milliliter of solution.
What is the pharmacotherapeutic effect of cyclosporine? Eye drops produce an anti-inflammatory, immunomodulating effect, inhibit the production of lacrimal secretion during dry keratoconjunctivitis.
How to use the drug "Restasis"
Locally used means "Restasis" containing cyclosporine. Instructions for use eye drops recommend first shake in a bottle to get a homogeneous opaque white emulsion. Only after this, you can begin to instill drops in the conjunctival sac of the patient’s eye. This procedure is carried out twice a day, every twelve hours. When using the medicine, you should not touch the edge of the bottle of the mucous membrane of the eye to prevent infection from entering the solution. It is important to remember that you need to use the drug immediately after opening the bottle, the remaining solution is no longer used, it is disposed of.
Do not carry out treatment with Restasis when wearing contact lenses. They are removed before using the solution, and you can insert it again after fifteen minutes.
Application for animals cyclosporine
Currently, this immunosuppressive agent is also used to treat autoimmune diseases in dogs and other animals.
Initially, cyclosporin was used only for humans. "Sandimmune" - an oil solution containing this substance, when used by different patients, caused a different concentration of the active component in the plasma.
Then a more modern form was created - ultra-micronized cyclosporine ("Neoral"). He caused the formation of microemulsions during interaction with the liquid. This has led to improved absorption and bioavailability of the drug, in contrast to the oil solution, which is not recommended for use in animals.
The creator of the veterinary form of the drug is considered the company Novartis. A licensed medication was released in 2003 under the name Atopic, and is intended for the treatment of atopic dermatitis in animals. Until that time, immunodepressants were unofficially used in kidney transplants for cats and dogs to eliminate the symptoms of inflammatory processes.
Signs of atopic dermatitis usually appear in young dogs and cats between the ages of six months and three years. This is a chronic disease characterized by periodic relapses. It requires lifelong treatment with a drug containing cyclosporine. Instructions for use for animals "Atopic" indicates the possibility of using it for a long period effectively and safely.
With the simultaneous intake of food and medication, changes in absorption are possible, therefore, it is recommended to take this drug two hours after or before meals.
Among the undesirable consequences from the use of the drug, the most common are disorders in the digestive system, but they appear in a mild form.Other side effects are signs of hypertrichosis, gum hyperplasia, and hyperplastic dermatitis. With a decrease in the dosage of the drug, they gradually disappear.
Reception of cyclosporine reduces the growth and development of causative agents of staphylococcal infections and malaysia dermatitis, in a therapeutic dose does not cause renal failure, hypertension, the formation of neoplasms. All these facts indicate a low level of risk of complications during long-term treatment of atopic dermatitis in dogs.