Immunosuppression

Question 1

What is the main purpose behind immunosuppressive drugs?

Answer 1

reduce clinical signs not cure

Question 2

What are their effects and how long does it usually take to come into effect?

Answer 2

immunomodulating (favour one while minimizing another)
mild immunosuppression
severe myelosuppresion
~couple weeks

Question 3

What is an example of a low end immunosuppresive?

Answer 3

glucocorticoids

- non-specific

Question 4

What are the uses and effects of glucocorticoids?

Answer 4

anti-inflammatory + immunosuppresive
- dependent on dose

altered leukocyte migration (decrease function of monocytes and macrophages, decrease lymphocyte function)
inhibits arachidonic acid = prevents leukotriene and prostaglandin

start aggressive and taper slow

Question 5

What glucocorticoids are there?

Answer 5

prednisone, prednisolone, dexamethazone, isoflupredone (predef)
short acting (dep-medtrol)
long acting (solu-delta-cortef

Question 6

What are three other immunosuppressive drugs that are more aggressive?

Answer 6

Azithioprine (Imuran)
Chlorambucil (leukeran)
Cyclosporine (atopica)

Question 7

What is the MOA, use and PK of Azathioprine?

Answer 7

MOA: purine antimetabolite (lymphocytes have to synthesize purine so they are susceptable)

PK: metabolized in the liver to active and inactive metabolites
USE: dogs, cats (more prone to bone marrow suppression)

Question 8

What is the risk of stopping Azathioprine immediately?

Answer 8

rebound hyper-immune response possible if not tapered

Question 9

What is the MOA, use and AE of Chlorambucil?

Answer 9

MOA: alkylating agent (cross links DNA)

USE: lymphocytic/plasmocytic infiltrative disease (inflammatory bowel disease), indolent ulcers, pemphigus, atopy

AE: myelosupresssion/vomitting, Fanconi’s syndrome (defective renal tubular reabsorption and neuro signs)

Question 10

What other purpose is Chlorambucil used for?

Answer 10

Chemotherapy

Question 11

What is the MOA, PK, use and AE of cylosporin?

Answer 11

MOA: inhibits cytoplasmic enzyme calcineurin (decrease IL-2), decrease cytokines (t-lymphocyte activation, chemotaxis, antigen prevention, decrease mast cell and eosinophil infiltration

USE: feline allergic dermatitis, feline immune mediated dermatoses (eosinophil granuloma/indolent ulcer), plasmacytic stomatitis
- topical (opthalmic)
compounded (capsule)

AE:vomiting, diarrhea, gingiva hyperplasia, secondary infections, Pgyp CYP substrates (drug interactions)

Question 12

What are two second line systemic immunosuppressant and their use?

Answer 12

Leflunomide
- used for rheumatoid arthritis in people
- inhibits pyrimadines in DNA
- prodrug
mycophenolate (mofetil)
- prodrug
- purine synthesis inhibitor
- inhibits T and B cell porliferation
- AE: diarrhea

Question 13

What is a topical immunosuppresive drug?

Answer 13

Tacrolimus (protopic)
- similar to cyclosporine (calcineuron/Tcell inhibitor)
USE: atopy

Question 14

What are two derm specific immunosuppressant (JET)?

Answer 14

apoquel (oclacitinib) and cytopoint (lokiyetmab)

Question 15

What are the MOA, use and AE of apoquel?

Answer 15

MOA: Janus kinase inhibitor (block cellualr communication - secondary mesenger pathway)
- JAK1 and 3 enzyme activity lowering IL31 (pruritic)

USE: pruritis with allergic dermatitis and atopic dermatitis
- rapid effect

AE: immunosuppression (secondary infection, demodicosis), low incidence of vomiting

Question 16

What is the MOA, use of cytopoint?

Answer 16

not a drug: monoclonal antibody IL31

USE: reduces pruritus in dogs with atopic dermatitis (doesn’t solve underlying problem)
can be used in multimodal therapy