Immunosuppressant Drug; Types, Side Effects, Interactions

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

• Rheumatoid arthritis
• Severe, active rheumatoid arthritis
• Ankylosing spondylitis 
• Psoriatic arthritis
• Ulcerative Colitis
• Juvenile idiopathic arthritis
• Juvenile rheumatoid arthritis
• Psoriasis
• Moderate to severe ulcerative colitis
• Giant Cell Arteritis
• Inflammatory Bowel Disease
• Neurosarcoidosis
• Plaque Psoriasis
• Polychondritis
• Psoriasis
• Pulmonary Fibrosis
• Sjogren’s Syndrome
• Spondyloarthritis
• Subcorneal pustular dermatosis
• Toxic epidermal necrolysis

Medical conditions treated with systemic corticosteroids

Allergy and respiratory medicine

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

• Tuberculosis
• Infection caused by Blastomyces dermatitides Fungus
• Opportunistic fungal infection
• Pneumonia 
• Severe infection
• Infection that lasts a long time
• Malignant melanoma
• Leukemia
• Diabetes that is not under control
• Reduction in the body’s resistance to infection
• The acquired decrease of all cells in the blood
• Low blood counts due to bone marrow failure
• Decreased neutrophils a type of white blood cell
• Multiple sclerosis
• Demyelinating Disease
• Sudden blindness and pain Upon moving the eye
• Heart failure
• Decreased Blood Platelets
• Decreased white blood cells
• Low Level of Granulocytes in the Blood
• Chronic heart failure
• Pneumonia caused by Legionella pneumophila bacteria
• Hardening of the liver caused by alcohol
• Liver inflammation caused by the body’s own immune response
• Seizures
• Reactivated tuberculosis
• Sepsis syndrome
• Malignant lymphoma
• Relapse of hepatitis B infection symptoms
• Hepatitis B
• Hepatosplenic T-cell lymphoma

Side Effects of Immunosuppressant Drug

The most common

• Nausea and vomiting
• Severe stomach ache
• multiple sclerosis,
• Severe diarrhea
• Vaginal thrush
• Skin rash redness or itching, pain, or swelling at the injection site
• A headache
• chest pain
• constipation
• a cough
• diarrhea or loose stools
• difficulty with breathing
• dizziness
• heartburn
• muscle pain

More common

• Abdominal or stomach pain, discomfort, or tenderness
• chills or fever
• difficulty with moving
• a headache, severe and throbbing
• joint or back pain
• Loss of energy or weakness
• pain or burning in the throat
• runny or stuffy nose
• muscle aching or cramping
• muscle pains or stiffness
• chest pressure or squeezing pain in the chest
• discomfort in arms, shoulders, neck or upper back
• excessive sweating
• feeling of heaviness, pain, warmth and/or swelling in a leg or in the pelvis
• sudden tingling or coldness in an arm or leg
• sudden slow or difficult speech
• sudden drowsiness or need to sleep
• fast breathing
• sharp pain when taking a deep breath
• fast or slow heartbeat
• coughing up blood
• rust colored urine
• decreased amount of urine

Rare

• Anxiety
• change in vision
• seizures
• abnormal or fast heart rate
• tremors
• weight loss
• chest pain or tightness
• confusion
• a cough
• Agitation
• arm, back, or jaw pain
• blurred vision
• chest pain or discomfort
• convulsions
• extra heartbeats
• fainting
• hallucinations
• a headache
• irritability
• lightheadedness
• mood or mental changes
• muscle pain or cramps
• muscle spasm or jerking of all extremities

Drug Interactions of Immunosuppressant Drug

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

• abatacept
• anakinra
• bacillus Calmette-Guérin (BCG)
• belimumab
• canakinumab
• certolizumab pegol
• cyclophosphamide
• denosumab
• fingolimod
• immunosuppressants (e.g., cyclosporine, mycophenolate, tacrolimus)
• medications that weaken the immune system (e.g., medications for cancer or organ transplants)
• other biologics (e.g., abatacept, adalimumab, infliximab, anakinra)
• leflunomide
• nivolumab
• natalizumab
• pimecrolimus
• roflumilast
• sulfasalazine
• tacrolimus
• tocilizumab
• tofacitinib
• trastuzumab
• vaccines (e.g., yellow fever, BCG, cholera, typhoid, varicella, meningococcal, diphtheria)
• vedolizumab

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

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