Week 7- Therapeutics For Haematopoietic System Immunosuppression

Question 1

What is vitamin K?

Answer 1

Fat-soluble vitamin in diet

Question 2

What is the Mode of Action for Vitamin K?

Answer 2

MoA - Co-factor in γ-carboxylation of Coagulation Factors II, VII, IX and X

Question 3

What is Vitamin K used for?

Answer 3

Vitamin K deficiency 2º to exocrine pancreatic deficiency
- Rodenticide poisoning – inhibit Vitamin K epoxide reductase which
produces active Vitamin K

Question 4

How should you administer Vitamin K?

Answer 4

Give slowly/ in IV

Question 5

Which factor runs out in the body first?

Answer 5

Factor 7

Question 6

What are heparins?

Answer 6

Family of glycosamines presnt in mast cells
- extracted from beef/ pig

Question 7

What is the MoA of heparins?

Answer 7

Inhibit coagulation by increasing affinity f antithrombin III to thrombin and other protease enzymes in the coagulation cascade

Question 8

What are the potential unwanted effects of Heparin?

Answer 8

Haemorrhage – stop/give protamine sulphate (heparin antagonist)
- Heparin-induced thrombocytopenia syndrome reported in humans
- Interacts with other drugs affecting coagulation e.g. aspirin/NSAIDs
- May antagonize corticosteroids / insulin; may increase diazepam levels

Question 9

What is the MoA of Aspirin?

Answer 9

Inhibits platelet thromboxane A2 synthesis – reduces platelet activation

Question 10

What are the unwanted effects of Aspirin?

Answer 10

GI ulceration and irritation etc
- Caution in renal disease

Question 11

What is the function of clopidrogel?

Answer 11

Antiplatelet drug

Question 12

What is the mode of action of Clopidrogel?

Answer 12

Prodrug - inhibits P2Y12 (an ADP-activated GPCR on platelets)
Used to reduce risk of thromboembolism

Question 13

What can clopidrogel be given alongside?

Answer 13

Can be given alongside aspirin

caution in hepatic and renal disease

Question 14

What is the mode of action of corticosteroids?

Answer 14

• Inhibits phospholipase II
• Inhibiting prostaglandin synthesis

Question 15

What is the function of glucocorticoids?

Answer 15

• Decrease neutrophil migration/ survival
• Decrease cytokines
• Lymphocyte apoptosis
• Decrease movement of inflammatory cells into tissues
• Supress macrophage function
• Reduced leucocyte trafficking
• Depressed lymphocyte activation

Question 16

Name 5 side effects of glucocorticoids

Answer 16

1. Increased production of dilute urine
2. Increased water consumption
3. Increased appetite
4. Panting
5. Tempermant changes

Question 17

What are some of the contraindications of corticosteroids?

Answer 17

• Pregnant animals
• DM
• Renal Insufficiency
• Corneal Ulceration
• Use alongside Live vaccines

Question 18

What is cyclosporine?

Answer 18

Potent, naturally occurring peptide (originally found in fungus)
Unlike azathioprine and chlorambucil, immunosuppressive but not cytotoxic

Question 19

What is the cyclosporine MoA?

Answer 19

complex – inhibits calcineurin, responsible for activating transcription of the immune system signalling cytokine IL-2 and reduces T-cell
proliferation/activity

Question 20

What is cyclosporine indicated for?

Answer 20

Chronic allergic dermatitis in cats
* Atopic dermatitis in dogs

Question 21

What is apoquel?

Answer 21

Janus kinase (JAK) inhibitor. Inhibits the function of a variety
of cytokines dependent on JAK enzyme activity (esp. IL-31)

Question 22

What is apoquel indicated in dogs for?

Answer 22

Treatment of pruritus - allergic dermatitis in dogs
* Treatment of atopic dermatitis in dogs

Question 23

What is cytopoint/ Lokivetmab?

Answer 23

caninised monoclonal antibody (mAb)
specifically targeting canine interleukin-31.

Question 24

What is lokivetmab indicated in dogs for?

Answer 24

Treatment of pruritus - allergic dermatitis in dogs
* Treatment of atopic dermatitis in dogs

Question 25

What is librela?

Answer 25

Monoclonal antibody to canine nerve growth factor (NGF).

Question 26

What is librela indicated in dogs for?

Answer 26

NGF involved in joint pathology and pain in OA. Leads to neurotransmitters (such as substance P and calcitonin generelated peptide [CGRP]) involved in nociception and causes the release of inflammatory mediators from immune cells

Question 27

What is the MoA of Azathioprine?

Answer 27

Cytotoxic - inhibits purine synthesis -> impacts DNA & RNA synthesis. Inhibits clonal proliferation during induction phase of immune response (cell- and antibody-mediated)

Question 28

What are the unwanted effects of azathioprine?

Answer 28

– Bone marrow suppression Monitor use closely – haematology every 1-2 weeks initially then 1-2 monthly – GI upset/anorexia, poor hair growth, acute pancreatitis, hepatotoxicity – Caution use in renal impairment/hepatic disease

Question 29

Why is azathioprine not recommended in cats?

Answer 29

Cats low in enzyme which metabolizes azathioprine so prone to toxicity (fatal leukopenia/thrombocytopenia)

Question 30

What is the MoA of Chlorambucil?

Answer 30

Cytotoxic – alkylating agent which cross-links DNA during all phases of the cell cycle, thus impeding replication

Question 31

What is the effect of chlorambucil?

Answer 31

Immunosuppressive effect in cats/dogs not well characterized Unwanted effects – Bone marrow suppression – Anorexia, nausea, vomiting. diarrhoea, poor hair growth – Neurotoxicity and seizures reported (rare)

Question 32

What is the MoA of cyclophosphamide?

Answer 32

Cytotoxic, alkylating agent, cross links DNA, impeding replication

Question 33

When is cyclophosphamide used?

Answer 33

Immune-mediated Disease and various cancers

Question 34

What are the unwanted effects of cyclophosphamide?

Answer 34

* Vomiting * Diarrhoea * Poor hair growth * Increased water Intake In Cats