Embedded Files
Introduction
Imagine the human body as a castle, and the immune system is the army that protects this castle from any outside attack—whether it’s a virus, bacteria, or any foreign invader. But sometimes, this army gets a little too excited, and instead of attacking the enemies, it starts attacking parts of its own castle!
That’s where the heroes of our story come in: Immunosuppressive agents.
The main job of these drugs is to “calm down” the immune system and make it think twice before launching an attack. This is super important in cases like organ transplantation or autoimmune diseases like lupus or rheumatoid arthritis. But of course, it’s not about calming it down too much—it has to be balanced so the body can still defend itself against real infections!
Mechanism of action
Mechanism of action
Mechanism of action
Mechanism of action
*»» Mechanism of Action of Immunosuppressive Drugs:
Immunosuppressive drugs work by modifying the function of the immune system in various ways to reduce its response in conditions where the immune activity is excessive, such as in autoimmune diseases or when preventing organ rejection in transplants. Here is a detailed explanation of their mechanisms of action:
» 1. Corticosteroids (e.g., Prednisolone)
Mechanism of Action:
Corticosteroids inhibit inflammatory cytokines like IL-1 and IL-6, reducing inflammation and weakening the immune response.
They prevent the activation of T-cells by affecting the gene signaling inside immune cells.
» 2. Calcineurin Inhibitors (e.g., Cyclosporine, Tacrolimus)
Mechanism of Action:
These drugs inhibit the enzyme calcineurin, which prevents T-cell activation by blocking the release of cytokines like IL-2.
This results in a general reduction of immune activity.
» 3. mTOR Inhibitors (e.g., Sirolimus, Everolimus)
Mechanism of Action:
These drugs inhibit the mTOR enzyme (Target of Rapamycin), which regulates cell growth and proliferation.
This inhibits the proliferation of T-cells and B-cells, reducing overall immune activity.
Primarily used in organ transplantation.
» 4. Anti-proliferation Drugs (e.g., Azathioprine, Mycophenolate)
Mechanism of Action:
These drugs inhibit the proliferation of immune cells by affecting DNA synthesis.
They prevent cell division and proliferation, reducing the number of immune cells.
» 5. Monoclonal Antibodies (e.g., OKT3)
Mechanism of Action:
These antibodies target activated or stimulated T-cells and prevent their activation by binding to specific receptors on the cell surface.
They are used primarily in cases of acute organ rejection.
» 6.Basiliximab
Mechanism of Action:
It binds to the alpha subunit (CD25) of the IL-2 receptor on activated T-cells, blocking IL-2-mediated activation and proliferation.
» 8.Belatacept:
Mechanism of Action:
Belatacept blocks CD80 and CD86 on antigen-presenting cells, preventing co-stimulatory signal via CD28, which inhibits T-cell activation.
» 9.Anti-Thymocyte Globulin (Thymoglobulin):
Mechanism of Action:
It is a polyclonal antibody preparation that targets multiple T-cell surface antigens, leading to their destruction and profound immunosuppression.
» 10.Daclizumab:
Mechanism of Action:
It targets the IL-2 receptor alpha chain (CD25) and inhibits IL-2 from binding, thus preventing T-cell proliferation.
*»» Common Mechanisms Among These Drugs
Cytokine Inhibition: Some drugs reduce the release of cytokines, which play a key role in activating the immune response.
T-cell Inhibition: All immunosuppressive drugs target T-cells in one way or another, either by preventing their proliferation or inhibiting their activation.
Cell Proliferation Modulation: Many drugs interfere with cellular proliferation in immune cells, limiting the generation of new cells involved in immune response.
_» These drugs regulate immune system reactions to reduce excessive immune activity that could harm organs or cause autoimmune diseases.
Brand name
Rapamune(sirolimus)
medrol(metylprednisolone)
imuran(Azathioprine)
Sandimmum(cyclosporine)
simulect(basiliximab)
rituxan(rituximab)
prgraf(tacrolimus)
indication
Immunosuppressants are medications that reduce the activity of the immune system. They are mainly used in situations where the immune response can harm the body, such as in organ transplants or autoimmune diseases.
1. Organ Transplantation
Immunosuppressants help prevent the body from rejecting a transplanted organ, such as:
Kidney transplant
Liver transplant
Heart transplant
Bone marrow transplant
Examples of medications:
Cyclosporine
Tacrolimus
Mycophenolate mofetil
Sirolimus
2. Autoimmune Diseases
In these cases, the immune system mistakenly attacks the body’s own tissues. Immunosuppressants help calm down this overreaction.
Examples of conditions:
Systemic Lupus Erythematosus (SLE)
Rheumatoid Arthritis (RA)
Multiple Sclerosis (MS)
Psoriasis
Crohn’s Disease & Ulcerative Colitis
Examples of medications:
Azathioprine
Methotrexate
Cyclophosphamide
Biologics like: Infliximab, Adalimumab
3. Blood Disorders
In conditions like aplastic anemia, immunosuppressants help allow the bone marrow to recover and produce blood cells.
Examples of medications:
Antithymocyte Globulin (ATG)
Cyclosporine
4. Certain Types of Cancer
Some immunosuppressants are used as part of chemotherapy or to treat immune-related cancers.
Example:
Certain types of leukemia and lymphoma
Rituximab is used to target B-cells
side effect
Immunosuppressant drugs are widely used to prevent organ rejection and treat autoimmune diseases. However, they can cause various side effects. Here, we’ll summarize these side effects, categorized by their main drug classes.
1. Calcineurin Inhibitors (Cyclosporine, Tacrolimus):
Nephrotoxicity
Hypertension
Neurotoxicity (e.g., tremors, headache, seizures)
Hyperglycemia (more common with Tacrolimus)
Hyperlipidemia
Gingival hyperplasia (Cyclosporine)
Hirsutism (Cyclosporine)
2. Antimetabolites (Azathioprine, Mycophenolate mofetil):
Bone marrow suppression (anemia, leukopenia, thrombocytopenia)
Gastrointestinal upset (nausea, diarrhea, abdominal pain)
Hepatotoxicity (especially Azathioprine)
Increased risk of infections
3. mTOR Inhibitors (Sirolimus, Everolimus):
Hyperlipidemia
Thrombocytopenia
Delayed wound healing
Oral ulcers
Interstitial lung disease (rare)
4. Corticosteroids (e.g., Prednisone):
Weight gain, Cushingoid features
Hyperglycemia
Osteoporosis
Mood changes, insomnia
Increased infection risk
Hypertension
Gastric ulcers
precautions& contraindications
Contraindications of Immunosuppressant Agents Categorized by drug class:
1. Calcineurin Inhibitors (Cyclosporine, Tacrolimus):
Hypersensitivity to the drug
Uncontrolled hypertension
Renal impairment (use with caution or avoid if severe)
Concurrent use with nephrotoxic drugs
Pregnancy (use only if benefits outweigh risks)
2. Antimetabolites (Azathioprine, Mycophen
Hypersensitivity to the drug
Severe hepatic impairment
Poor wound healing (e.g., recent surgery)
Pulmonary disorders (e.g., interstitial lung disease)
4. Corticosteroids (e.g., Prednisone):
Systemic fungal infections
Hypersensitivity to the drug
Live vaccines (avoid during high-dose therapy)
Use with caution in diabetes, osteoporosis, and peptic ulcer disease
5. Biologics (e.g., Basiliximab, Rituximab):
Hypersensitivity or previous severe infusion reaction
Active or latent infections (especially TB or hepatitis B)
Pregnancy and breastfeeding (caution advised)
Live vaccines (contraindicated during and shortly after treatment)
Precautions When Using Immunosuppressive Drugs:
1. Avoid Infections:
Practice good hygiene and stay away from sick people or crowded places.
2. Vaccinations:
Avoid live vaccines during treatment. Get necessary vaccines before starting.
3. Regular Checkups:
Do frequent blood tests to monitor immune cells, liver, and kidney function.
4. Sun Protection:
Use sunscreen and limit sun exposure to reduce the risk of skin cancer.
5. Pregnancy & Breastfeeding:
Consult your doctor—some drugs can harm the baby or pass through breast milk.
6. Drug Interactions:
Always tell your doctor about any meds or supplements you're taking.
references
Monographs
Monographs
Document from Sohila Ehab.pdfDocument from Sohila Ehab.pdfDocument from Sohila Ehab.pdfDocument from Sohila Ehab.pdfDocument from Sohila Ehab.pdfDocument from Sohila Ehab.pdfDocument from Sohila Ehab.pdfPage updated
Report abuse