23. Immunosuppressive drugs

Question 1

What are immunosuppressive drugs?

Answer 1

Immunosuppressants are drugs that reduce the activity of the immune system. They are crucial in managing conditions where the immune system is overactivated or misdirected

Question 2

Indications for use of immunosuppressive drugs

Answer 2

1. Autoimmune diseases
The immune system attacks the body’s own tissues
2. Hypersensitivty diseases
Atopic dermaitisi, IBS
3. Transplantation
To prevent the immune system from rejecting a transplanted organ

Question 3

Autoimmune diseases

Answer 3

1. Lupus Autoimmune disease, affects the skin and other organs

2. Immune-mediated haemolytic anaemia Immune system destroys red blood cells

Question 4

Different drug groups used as immunosuppressive agents:

Answer 4

1. Antimetabolites
2. Cytokine gene expression inhibitors

Question 5

Antimetabolites, Active substances:

Answer 5

• Azathioprine ⭢ Active form: Mercaptopurine
• Mycophenolate mofetil ⭢ Active form: Mycophenolic acid

Question 6

Antimetabolites, mechanism of action:

Answer 6

They work by inhibiting the DNA damage, which will prevent cells and especially immune cells, from replicating.

Question 7

Antimetabolites, azathioprine:

Answer 7

It is a prodrug, meaning it is converted into its active form in the body; the active form is mercaptopurine.
It acts as a purine analogue; it combines with ribose and phosphate to form a nucleotide, which will interfere with DNA synthesis, and this will disrupt cell replication.

The drug is released slowly in the body, giving a long-lasting effect.

administration: Per os or IV
It has side effects, especially in Fe, which can lead to iron deficiency

Question 8

Antimetabolites, mycophenolate mofetil:

Answer 8

A prodrug which is given orally.

It is converted into mycophenolic acid by an enzyme in the blood called plasma esterase.

Mycophenolate-mofetil inhibits the enzyme called inosine monophosphate dehydrogenase, this enzyme is crucial in making GMP (Guanosine monophosphate), a building block of DNA. By inhibiting this enzyme, the drug reduces the availability of GMP and reduces DNA synthesis.
The drug is particularly effective in T and B lymphocytes because they rely on specific pathways (“de novo”). Other cells have a salvage pathway that makes them less vulnerable to the drug.
It is considered safer than azathioprine, with fever GI-tract and bone marrow side effects. Not commonly used in veterinary medicine, but can be used in case of kidney inflammation

Question 9

Cytokine Gene Expression Inhibitors, Active substances:

Answer 9

• Cyclosporine
• Tacrolimus
• Pimecrolimus

Question 10

Cyclosporine, mechanism of action:

Answer 10

Cyclosporine blocks calcineurin, which normally activates a protein called NFAT, which then moves into the nucleus of the cell to produce IL-2 (interleukin-2). IL-2 is essential for activating the T-cells.

Cyclosporine only works in T-cells !!

Cyclosporine also inhibits the mast cells, preventing them from releasing substances that cause inflammation. This will lead to the production of inflammatory substances like IL and TNF-α.

Question 11

Cyclosporine, application:

Answer 11

Very commonly used medication.

It can be given orally, with food to help absorption! It can also be applied directly to the affected area.

Question 12

Cyclosporine, indication:

Answer 12

• Auto-immune diseases: lupus, Keratoconjunctivitis sicca
• Atopic dermatitis
• Inflammatory bowel disease

Question 13

Cyclosporine, side effects:

Answer 13

• Problems with kidney and liver in cats and dogs.
• GI-tract issues: vomiting, diarrhoea
• Hair loss (Alopecia)
• overgrowth of the gums (gingival hyperplasia)