Immunosuppressant Drugs - Classification | Medical Science Optional Notes for UPSC PDF Download

Introduction

1. Calcineurin Inhibitors (Specific T-cell Inhibitors):

• Cyclosporine (Ciclosporin)
• Tacrolimus

2. m-TOR Inhibitors:

• Sirolimus
• Everolimus

3. Antiproliferative Drugs (Cytotoxic Drugs):

• Azathioprine
• Methotrexate
• Cyclophosphamide
• Chlorambucil
• Mycophenolate Mofetil (MMF)

4. Glucocorticoids:

• Prednisolone

5. Biological Agents:
(a) TNFα Inhibitors:

• Etanercept
• Infliximab
• Adalimumab

(b) IL-1 Receptor Antagonist: Anakinra
(c) IL-2 Receptor Antagonists (anti-CD-25 antibodies):

• Daclizumab
• Basiliximab

(d) Anti-CD-3 Antibody: Muromonab CD3
(e) Polyclonal Antibodies:

• Antithymocyte Antibody (ATG)
• Rho (D) Immune Globulin

Calcineurin Inhibitors

Cyclosporine Drug - Interactions

Nephrotoxicity: The nephrotoxic effects of drugs such as aminoglycosides, vancomycin, amphotericin B, and NSAIDs are heightened.

Microsomal Enzyme Induction

Hyperkalemia

Potassium supplements and K+ sparing diuretics

mTOR Inhibitors

Advantage of Sirolimus over Calcineurin Inhibitors

• In individuals experiencing nephrotoxicity associated with calcineurin inhibitors, switching to sirolimus has shown effectiveness in preventing rejection and concurrent improvements in renal function.

• Due to its significant antiproliferative effects, sirolimus has been proposed as a valuable immunosuppressive agent for individuals with a history or current presence of malignancies, such as hepatocellular carcinoma (HCC).

• Sirolimus-coated stents are employed to decrease the occurrence of coronary artery restenosis by inhibiting endothelial proliferation at the site.

• Sirolimus has demonstrated efficacy in some cases resistant to steroids and has been utilized in stem cell transplantation.

Note: Sirolimus is not officially approved for use in liver transplant recipients due to reported associations with an increased incidence of hepatic artery thrombosis in the first month post-transplantation.

Cytotoxic Immunosuppressant Drugs

Methotrexate Mechanism of Action

Pemetrexed

• A more recent analogue of MTX.
• Mainly focuses on thymidylate synthase.
• Does not impact the pool of THFR.
• Adverse effects closely resemble those of MTX.
• Hand-foot syndrome manifests as a painful, itchy, erythematous rash affecting the hands and feet (treated with dexamethasone).
• Approved for the treatment of mesothelioma and non-small cell lung carcinoma in combination with cisplatin.

Cytotoxic Immunosuppressant Drugs

Immunosuppressant Drugs - Repeats

• Provide the mechanism of action, therapeutic uses, and adverse effects of Methotrexate (1998).
• Examine the mechanism of action, therapeutic uses, and adverse effects of Methotrexate (2000).
• Classify immunosuppressive drugs and briefly describe the mechanism of action and side effects of cyclosporine. Highlight the advantages of sirolimus as an immunosuppressant (2012).
• Outline the mechanism of action of Cyclophosphamide and detail its adverse effects (2014).