Immunosuppressant Drug; Types, Side Effects, Interactions

Immunosuppressant drug








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Immunosuppressant drug is a kind of agent or drugs that suppress the immune system and reduce the risk of rejection of foreign bodies such as transplant organs. Different classes of immunosuppressive agents have different mechanism of action. Now immunosuppressive agents are used as cancer chemotherapy.  It is used primarily to prevent the rejection of an organ following transplantation and in the treatment of autoimmune disease. They are used in immunosuppressive therapy to prevent the rejection of transplanted organs and tissues (e.g., bone marrow, heart, kidney, liver). Treat autoimmune diseases or diseases that are most likely of autoimmune origin (e.g., rheumatoid arthritis, multiple sclerosis, myasthenia gravis, psoriasis, vitiligo, granulomatosis with polyangiitis, systemic lupus erythematosus, sarcoidosis, focal segmental glomerulosclerosis, Crohn’s disease, Behcet’s Disease, pemphigus, and ulcerative colitis). Treat some other non-autoimmune inflammatory diseases (e.g., long-term allergic asthma control), ankylosing spondylitis.

Types of Immunosuppressant Drug

Immunosuppressive drugs can be classified into five groups

  • Glucocorticoids
  • Cytostatics
  • Antibodies
  • Drugs acting on immunophilins
  • Other drugs

Depending on these factors, approaches could include

  • Induction immunosuppression. This approach includes all medications given immediately after transplantation in intensified doses for the purpose of preventing acute rejection. Although the drugs may be continued after discharge for the first 30 days after transplant, they are not used long-term for immunosuppressive maintenance. Associated medications can include Methylprednisolone, Atgam, Thymoglobulin, OKT3, Basiliximab or Daclizumab.
  • Maintenance immunosuppression – Maintenance includes all immunosuppressive medications given before, during or after transplant with the intention to maintain them long-term. For example, Prednisone, Cyclosporine, Tacrolimus, Mycophenolate Mofetil, Azathioprine or Rapamycin. In addition, maintenance immunosuppression does not include any immunosuppressive medications given to treat rejection episodes, or for induction.
  • Anti-rejection immunosuppression – This approach includes all immunosuppressive medications given for the purpose of treating an acute rejection episode during the initial post-transplant period or during a specific follow-up period, usually up to 30 days after the diagnosis of acute rejection. Associated medications can include Methylprednisolone, Atgam, OKT3, Thymoglobulin, Basiliximab or Daclizumab.

Overall classification of Immunosuppressant Drug

Monoclonal

Mechanism of actions of Immunosuppressant Drug

Glucocorticoids suppress the cell-mediated immunity. They act by inhibiting genes that code for the cytokines Interleukin 1 (IL-1), IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, and TNF-alpha, the most important of which is IL-2. Smaller cytokine production reduces the T cell proliferation.Glucocorticoids also suppress the humoral immunity, causing B cells to express smaller amounts of IL-2 and IL-2 receptors. This diminishes both B cell clone expansion and antibody synthesis.Glucocorticoids influence all types of inflammatory events, no matter their cause. They induce the lipocortin-1 (annexin-1) synthesis, which then binds to cell membranes preventing the phospholipase A2from coming into contact with its substrate arachidonic acid. This leads to diminished eicosanoid production. The cyclooxygenase (both COX-1 and COX-2) expression is also suppressed, potentiating the effect.

Glucocorticoids also stimulate the lipocortin-1 escaping to the extracellular space, where it binds to the leukocyte membrane receptors and inhibits various inflammatory events: epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst, and the release of various inflammatory mediators (lysosomal enzymes, cytokines, tissue plasminogen activator, chemokines, etc.) from neutrophils, macrophages, and mastocytes.

Indications/ Uses of Immunosuppressant Drug

Medical conditions treated with systemic corticosteroids

Allergy and respiratory medicine

  • Asthma (severe exacerbations)
  • Chronic obstructive pulmonary disease (COPD)
  • Allergic rhinitis
  • Atopic dermatitis
  • Hives
  • Angioedema
  • Anaphylaxis
  • Food allergies
  • Drug allergies
  • Nasal polyps
  • Hypersensitivity pneumonitis
  • Sarcoidosis
  • Eosinophilic pneumonia
  • Some other types of pneumonia (in addition to the traditional antibiotic treatment protocols)
  • Interstitial lung disease

Dermatology

  • Pemphigus Vulgaris
  • Contact dermatitis

Endocrinology (usually at physiologic doses)

  • Addison’s Disease
  • Adrenal insufficiency
  • Congenital adrenal hyperplasia

Gastroenterology

  • Ulcerative colitis
  • Crohn’s disease
  • Autoimmune hepatitis

Hematology

  • Lymphoma
  • Leukemia
  • Hemolytic anemia
  • Idiopathic thrombocytopenic purpura
  • Multiple Myeloma

Rheumatology/Immunology

  • Rheumatoid arthritis as
  • Systemic lupus erythematosus
  • Polymyalgia rheumatica
  • Polymyositis
  • Dermatomyositis
  • Polyarteritis
  • Vasculitis

Ophthalmology

  • Uveitis
  • Keratoconjunctivitis

Other conditions

  • Multiple sclerosis
  • Organ transplantation
  • Nephrotic syndrome
  • Chronic hepatitis (flare-ups)
  • Cerebral edema
  • IgG4-related disease
  • Prostate cancer
  • Tendinosis
  • Lichen planus

Topical formulations are also available for the skin, eyes (uveitis), lungs (asthma), nose (rhinitis), and bowels. Corticosteroids are also used supportively to prevent nausea, often in combination with 5-HT3 antagonists.

Contra-Indications of Immunosuppressant Drug

Side Effects of Immunosuppressant Drug

The most common

More common

Rare

Drug Interactions of Immunosuppressant Drug

Immunosuppressant drugs  may interact with the following drugs, supplements, & may change the efficacy of the drug

Some associate drug interactions

  • On the other hand, phenobarbital, ephedrine, phenytoin, and rifampin may reduce the blood levels of corticosteroids by increasing the breakdown of corticosteroids by the liver. This may necessitate an increase of corticosteroid dose when they are used in combination with these drugs.
  • Estrogens have been shown to increase the effects of corticosteroids possibly by decreasing their breakdown by the liver.
  • Corticosteroid effects on warfarin can vary; therefore when taking warfarin along with corticosteroids, there may be an increased need for monitoring coagulation levels more closely.
  • Low blood potassium (hypokalemia) and a higher chance of heart failure can result from combining corticosteroids with drugs that reduce potassium in the blood (for example, diuretics, amphotericin B).
  • Anticholinesterase drugs (for example, physostigmine) may cause severe weakness in some patients with myasthenia gravis when prescribed with corticosteroids.
  • Corticosteroids can increase blood glucose, so close monitoring of blood sugar and higher doses of diabetes medications may be needed.
  • Cholestyramine (Questran, Questran Light) can decrease the absorption of oral corticosteroids from the stomach and this could reduce the blood levels of corticosteroids.

References

Immunosuppressant drug

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