Name of the Topic: Short note on Immunosuppressive drugs

Examination: 1st Continuous Assessment (1st CA)

Name: Suvojit Basak
Roll Number: 35601921045
Registration Number: 213560201910045
Semester: 6th
Year: 3rd
Subject: Pharmacology III
Paper Code: PT 618
Academic Session: 2023-2024

Global College of Pharmaceutical Technology

(A Unit of National Centre for Development of Technical Education)
 I M M U N O S U P P R E S S A S I V E DRUGS

 IMMUNOSUPPRESSANTS:
These are those drugs which inhibit the immunity. They may supress cell-mediated or
humoral immunity or both.
• It is necessary to supress immune reaction in organ transplantation & in autoimmune disorders.

 CLASSIFICATION:
1. Calcineurin inhibitors- Cyclosporine, Tacrolimus
2. mTOR (mammalian target of rapamycin) inhibitors- Sirolimus, Everolimus
3. Antiproliferative & Cytotoxic agents- Azathioprine, Methotrexate, Cyclophosphamide
4. Glucocorticoids- Prednisolone, Methylprednisolone
5. Immunosuppressant antibodies- Infliximab, Muromonab CD3, Anti-Rh (D) immunoglobulin
6. Others- Hydroxychloroquine
 CALCINEURIN INHIBITORS:
Cyclosporine: It is a cyclic peptide antibiotic. Very lipophilic & not soluble in nature.
• Mechanism of action:
enters in target cells
↓
binds to cyclophilin
↓
cyclosporine – cyclophilin complex
↓
inhibit calcineurin and blocks activation of T cells and decreased
production of IL-2 and other cytokines.
• Pharmacokinetics: Administered through oral & IV route. It is metabolized by microsomal enzymes cytochrome
P450 in liver.
• Uses:
1. To prevent & treat rejection episodes in organ transplantation like kidney, bone marrow, liver etc.
2. Treat autoimmune disease like myasthenia gravis, rheumatoid arthritis etc.
• Adverse effect: Nephrotoxicity, Hepatotoxicity, Hypertension, Hyperglycemia, Liver disfunction.

Tacrolimus: A macrolide antibiotic. MOA is same to Cyclosporine except that it binds to different immunophill in and
inhibits calcineurin.
• More potent than Cyclosporine
• Given orally and parenterally.
 mTOR INHIBITORS:
Sirolimus: It inhibits the T cell activation.
• Mechanism of action:
It forms complex with an immunophilin
↓
Inhibits a key enzyme in cell cycle progression
↓
Inhibits the response of interleukin-2
↓
That blocks activation of T-cells and B-cells

• Pharmacokinetics: Given orally & topically, Half life is about 60 hours, metabolised in liver & excreted through
faeces.
• Uses: Used alone or in combination with other drugs for the prophylaxis of organ transplant rejection. May be
used as a alternative to calcineurin inhibitors
• Adverse effect: Headache, Hepatotoxicity, Risk of infection, Hypokalaemia.

Everolimus: Similar to Sirolimus.

 ANTIPROLIFERATIVE & CYTOTOXIC AGENTS:
Azathioprine: It is a prodrug of purine analogue- mercaptopurine.
• Mechanism of action:
Taken up into the immune cells
↓
Activated to 6-MP
↓
Inhibits purine synthesis
↓
Inhibition of cell Proliferation and impairment of lymphocyte function

• Pharmacokinetics: Given orally or through IV, does not cross BBB, metabolized in liver, excreted primarily
through urine.
• Uses:
1. Used in combination with glucocorticoids or cyclosporine for prevention of rejection in organ transplant.
2. Used in rheumatoid arthritis & Crohn's disease.
• Adverse effect: Hepatotoxicity, bone marrow suppression, Gastrointestinal side effects.
• Cyclophosphamide & Methotrexate are also used for immunosuppressive properties.
 GLUCOCORTICOIDS:
Prednisolone: It induce redistribution of lymphocytes that decrease in peripheral blood lymphocyte count.
• Mechanism of action:
Inhibit proliferation of T-lymphocytes
↓
Decrease expression of interleukins
↓
Blocks the activation of T-cells and B-cells

• Pharmacokinetics: Given orally & parenterally.

• Uses: Used in the combination with other immunosuppressant drugs.
1. To prevent and treat rejection episodes during organ transplantation.
2. In autoimmune diseases.
• Adverse effect: Osteoporosis, Hyperglycemia, Risk of infection.
 IMMUNOSUPPRESSANT ANTIBODIES:
Infliximab: It is a monoclonal antibody & blocks TNF a.
• Mechanism of action:
It forms a relatively stable complex
↓
Binds to soluble and membrane bound TNF a.
↓
That blocks activation of T-lymphocytes

• Pharmacokinetics: Given through IV. Half life is 9-10 days. Metabolized in liver & excreted through urine.
• Uses: Rheumatoid arthritis, Crohn’s disease
• Adverse effect: Infusion reactions like fever, urticaria, hypotension.

• Other monoclonal anti-IL-2 receptor antibodies are Basiliximab & Dacilizumab, blocks the binding of interleukin-
2 to the lymphocytes & halt the immune process.
Muromonab CD3: It is a murine monoclonal antibody. Prepared from hybridoma technology.
• Mechanism of action:
Drug binds to CD3 protein on T lymphocytes
↓
Lead to transient activation & cytokine release
↓
Disruption of T lymphocyte function, their depletion and decreased immune response.

• Pharmacokinetics: Administered through IV. Metabolised & excreted in bile.

• Uses: Used for the treatment of acute renal allograft rejection & steroid resistant acute allograft.
• Adverse effect: Fever, CNS effects, Infection.
Anti-Rh (D) immunoglobulin:
• When Rh negative mother delivers an Rh positive baby or aborts, the Rh positive antigens from the red cells of
foetus enters into maternal bloodstream.
• This sensitizes the mother to produce antibodies against Rh positive cells.
• In subsequent pregnancies, the maternal antibodies against Rh positive cells reach the foetus and may result in
haemolytic disease of new born.
• Injection of anti-Rh (D) immunoglobin to the mother at the time of child birth or after abortion will bind the
antigens on the RBCs of the baby which has entered the maternal circulation.
• This will prevent the formation of antibodies in the Rh negative mother against the Rh positive RBCs.
• Thus subsequent pregnancies would not be affected.
• The immunoglobin should be given within 24-72 hours of child birth to prevent haemolytic disease.
• Adverse effect: Local pain, Fever.

 OTHER DRUGS:
• Hydroxychloroquine, an antimalarial drug like chloroquine, also has immunosuppressant and anti-inflammatorty
properties for which it is used in rheumatoid arthritis.
 CONCLUSION:
Immunosuppressive drugs play a critical role in modern medicine, providing essential therapeutic
options for patients with autoimmune and inflammatory conditions, as well as those undergoing organ transplantation.
Despite their challenges, ongoing research and innovations offer promising prospects for the future of
immunosuppressive drug therapy.