Immunosuppressants Pharmacology
Immunosuppressants
• Define what is meant by immune manipulation
• List the different approaches to immune manipulation
• Classify immunosuppressive medicines giving examples
• Explain pharmacodynamics, pharmacokinetics, indications, therapeutic efficacy, adverse effects, cautions,
contraindications, interactions with medicines, cost and availability of immunosuppressive medicines including:
♣ Azathioprine ♣ Mycophenolate mofetil ♣ Calcineurin inhibitors ♣ Cyclophosphamide ♣ Sirolimus
• List some commonly used polyclonal and monoclonal antibodies giving examples, their cost, common uses,
precautions and adverse effects
Immune manipulation
Immune manipulation refers to the deliberate alteration or modulation of the immune system's
activity, either to enhance or suppress its function.
1. Immunostimulants
a. Act as immunopotentiators
b. Enhancing the basic level of immune response.
2. Immunosuppressants
a. Used to treat
• organ transplant rejection (alloimmunity)
• autoimmune diseases
b. Structurally and functionally heterogeneous group of drugs
c. Often concomitantly administered in combination regimens
Mechanisms of Immunosuppressants
1. Drugs that inhibit purine synthesis
azathioprine, mycophenolate mofetil, methotrexate
Piyumal Fernando 1
, Immunosuppressants Pharmacology
2. Drugs that inhibit pyrimidine synthesis
Leflunomide
3. Drugs that inhibit expression cytokines
IL-2: - ciclosporin, tacrolimus (Calcineurin inhibitors)
TNF and others: - Sulfasalazine, hydroxychloroquine, thalidomide
4. Inhibit IL-2R signalling –
Sirolimus, everolimus
5. Cytokine blockade (antibodies)
Infliximab Etanercept Adalilumab Ankinra Tocilizumab
6. Cytotoxicity – damage to DNA - cyclophosphamide
01. Azathioprine
De novo synthesis of purines
• Involves 4 major steps
o PRPP (5-phosphoribosyl-1-pyrophosphate) synthesis
ribose-5-phosphate → PRPP
o Phosphoribosylamine synthesis (amidotransferase reaction)
o Synthesis of the common precursor – IMP
o Conversion to IMP to GMP & AMP
Salvage synthesis of purines
• Uses catabolic products of nucleic acids (purine bases) to resynthesize nucleotide
monophosphate.
Mechanism of action
• Azathioprine undergoes reduction in the presence of glutathione to 6-mercaptopurine and
then to 6-thioguanine.
• This forms a false purine nucleotide that is then incorporated into DNA, thus inhibiting DNA
replication and cell proliferation. It may also trigger apoptosis.
• These actions result in
o Reduction in circulating B and T lymphocytes
Piyumal Fernando 2
Immunosuppressants
• Define what is meant by immune manipulation
• List the different approaches to immune manipulation
• Classify immunosuppressive medicines giving examples
• Explain pharmacodynamics, pharmacokinetics, indications, therapeutic efficacy, adverse effects, cautions,
contraindications, interactions with medicines, cost and availability of immunosuppressive medicines including:
♣ Azathioprine ♣ Mycophenolate mofetil ♣ Calcineurin inhibitors ♣ Cyclophosphamide ♣ Sirolimus
• List some commonly used polyclonal and monoclonal antibodies giving examples, their cost, common uses,
precautions and adverse effects
Immune manipulation
Immune manipulation refers to the deliberate alteration or modulation of the immune system's
activity, either to enhance or suppress its function.
1. Immunostimulants
a. Act as immunopotentiators
b. Enhancing the basic level of immune response.
2. Immunosuppressants
a. Used to treat
• organ transplant rejection (alloimmunity)
• autoimmune diseases
b. Structurally and functionally heterogeneous group of drugs
c. Often concomitantly administered in combination regimens
Mechanisms of Immunosuppressants
1. Drugs that inhibit purine synthesis
azathioprine, mycophenolate mofetil, methotrexate
Piyumal Fernando 1
, Immunosuppressants Pharmacology
2. Drugs that inhibit pyrimidine synthesis
Leflunomide
3. Drugs that inhibit expression cytokines
IL-2: - ciclosporin, tacrolimus (Calcineurin inhibitors)
TNF and others: - Sulfasalazine, hydroxychloroquine, thalidomide
4. Inhibit IL-2R signalling –
Sirolimus, everolimus
5. Cytokine blockade (antibodies)
Infliximab Etanercept Adalilumab Ankinra Tocilizumab
6. Cytotoxicity – damage to DNA - cyclophosphamide
01. Azathioprine
De novo synthesis of purines
• Involves 4 major steps
o PRPP (5-phosphoribosyl-1-pyrophosphate) synthesis
ribose-5-phosphate → PRPP
o Phosphoribosylamine synthesis (amidotransferase reaction)
o Synthesis of the common precursor – IMP
o Conversion to IMP to GMP & AMP
Salvage synthesis of purines
• Uses catabolic products of nucleic acids (purine bases) to resynthesize nucleotide
monophosphate.
Mechanism of action
• Azathioprine undergoes reduction in the presence of glutathione to 6-mercaptopurine and
then to 6-thioguanine.
• This forms a false purine nucleotide that is then incorporated into DNA, thus inhibiting DNA
replication and cell proliferation. It may also trigger apoptosis.
• These actions result in
o Reduction in circulating B and T lymphocytes
Piyumal Fernando 2
