Week 7- Therapeutics For Haematopoietic System Immunosuppression Flashcards
What is vitamin K?
Fat-soluble vitamin in diet
What is the Mode of Action for Vitamin K?
MoA - Co-factor in γ-carboxylation of Coagulation Factors II, VII, IX and X
What is Vitamin K used for?
Vitamin K deficiency 2º to exocrine pancreatic deficiency
- Rodenticide poisoning – inhibit Vitamin K epoxide reductase which
produces active Vitamin K
How should you administer Vitamin K?
Give slowly/ in IV
Which factor runs out in the body first?
Factor 7
What are heparins?
Family of glycosamines presnt in mast cells
- extracted from beef/ pig
What is the MoA of heparins?
Inhibit coagulation by increasing affinity f antithrombin III to thrombin and other protease enzymes in the coagulation cascade
What are the potential unwanted effects of Heparin?
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
What is the MoA of Aspirin?
Inhibits platelet thromboxane A2 synthesis – reduces platelet activation
What are the unwanted effects of Aspirin?
GI ulceration and irritation etc
- Caution in renal disease
What is the function of clopidrogel?
Antiplatelet drug
What is the mode of action of Clopidrogel?
Prodrug - inhibits P2Y12 (an ADP-activated GPCR on platelets)
Used to reduce risk of thromboembolism
What can clopidrogel be given alongside?
Can be given alongside aspirin
caution in hepatic and renal disease
What is the mode of action of corticosteroids?
- Inhibits phospholipase II
- Inhibiting prostaglandin synthesis
What is the function of glucocorticoids?
- Decrease neutrophil migration/ survival
- Decrease cytokines
- Lymphocyte apoptosis
- Decrease movement of inflammatory cells into tissues
- Supress macrophage function
- Reduced leucocyte trafficking
- Depressed lymphocyte activation
Name 5 side effects of glucocorticoids
- Increased production of dilute urine
- Increased water consumption
- Increased appetite
- Panting
- Tempermant changes
What are some of the contraindications of corticosteroids?
- Pregnant animals
- DM
- Renal Insufficiency
- Corneal Ulceration
- Use alongside Live vaccines
What is cyclosporine?
Potent, naturally occurring peptide (originally found in fungus)
Unlike azathioprine and chlorambucil, immunosuppressive but not cytotoxic
What is the cyclosporine MoA?
complex – inhibits calcineurin, responsible for activating transcription of the immune system signalling cytokine IL-2 and reduces T-cell
proliferation/activity
What is cyclosporine indicated for?
Chronic allergic dermatitis in cats
* Atopic dermatitis in dogs
What is apoquel?
Janus kinase (JAK) inhibitor. Inhibits the function of a variety
of cytokines dependent on JAK enzyme activity (esp. IL-31)
What is apoquel indicated in dogs for?
Treatment of pruritus - allergic dermatitis in dogs
* Treatment of atopic dermatitis in dogs
What is cytopoint/ Lokivetmab?
caninised monoclonal antibody (mAb)
specifically targeting canine interleukin-31.
What is lokivetmab indicated in dogs for?
Treatment of pruritus - allergic dermatitis in dogs
* Treatment of atopic dermatitis in dogs
What is librela?
Monoclonal antibody to canine nerve growth factor (NGF).
What is librela indicated in dogs for?
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
What is the MoA of Azathioprine?
Cytotoxic - inhibits purine synthesis -> impacts DNA & RNA synthesis.
Inhibits clonal proliferation during induction phase
of immune response (cell- and antibody-mediated)
What are the unwanted effects of azathioprine?
– 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
Why is azathioprine not recommended in cats?
Cats low in enzyme which metabolizes azathioprine
so prone to toxicity (fatal leukopenia/thrombocytopenia)
What is the MoA of Chlorambucil?
Cytotoxic – alkylating agent which cross-links DNA during
all phases of the cell cycle, thus impeding replication
What is the effect of chlorambucil?
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)
What is the MoA of cyclophosphamide?
Cytotoxic, alkylating agent, cross links DNA, impeding replication
When is cyclophosphamide used?
Immune-mediated Disease and various cancers
What are the unwanted effects of cyclophosphamide?
- Vomiting
- Diarrhoea
- Poor hair growth
- Increased water Intake In Cats
