Haematopoeitic Therapeutics

Question 1

Cyclophosphamide (cytoxan), doxorubicin (adriamycin), vincristine (oncovin), prednisolone, L-asparaginase (CHOP)

Answer 1

• Chemotherapy
• Canine + feline lymphoma

Question 2

Chlorambucil

Answer 2

• Chemo
• Chronic lymphocytic leukaemia (CLL)

Question 3

Vitamin K (e.g. Konakion MM, phytomenadione)

Answer 3

• Co-factor in gamma-carboxylation of F II, VII, IX and X
• SC/PO
• Vitamin K-dependent coagulopathies (bleeding disorders): vit K deficiency 2y to pancreatic deficiency, rodenticide poisoning

Question 4

Heparin & low molecular weight heparins (LMWHs)

Answer 4

• Glycosaminoglycans present in mast cells
• Extracted from beef/pig
• Inhibit coagulation by increasing affinity of antithrombin III to thrombin + other protease enzymes in coagulation cascade
• Heparin IV/SC (not IM - causes hematomas)
• LMWHs SC
• Promotion of anticoagulation: maintenance of IV catheter placement (heparin), prevention of 2y thromboembolic disease, disseminated intravascular coagulation (DIC) (controversial)
• AE: haemorrhage (stop, give antagonist for heparin = protamin sulfate); heparin-induced thrombocytopenia; interacts w/ other drugs affecting coagulation e.g. aspirin/NSAIDs; may antagonise corticosteroids/insulin -> may inc diazepam levels

Question 5

Aspirin

Answer 5

• NSAID, antiplatelet
• Inhibits platelet thromboxane A2 synthesis - reduced platelet activation
• AE: GI ulceration + irritation; caution in renal disease

Question 6

Clopidogrel

Answer 6

• Antiplatelet
• Prodrug - inhibits P2Y12 (an ADP-activated GPCR on platelets)
• Can be given w/ aspirin
• AE: Caution in hepatic + renal disease, has bad taste
• Dec risk of thromboembolism

Question 7

Prednisolone

Answer 7

• Oral glucocorticoid
• Immunosuppressant
• Companion animals
• Can be given w/ azathioprine (not cats), cyclophosphamide, cyclosporin, chlorambucil adjuvant agents
• Immune-mediated haemolytic anaemia (IMHA); Immune-Mediated Thrombocytopenia (IMTP); eosinophilia; leukaemia
• (Give gastroprotective therapy - e.g. H2 antagonist or omeprazole)
• AE: Care w/ giving for hypothalamic-pituitary-adrenal (HPA) axis, high dose may shut adrenal glands down -> dec steroid production; may antagonise effect of insulin
• Contraindicated: pregnant animals, diabetes mellitus, renal insufficiency, corneal ulceration, alongside live vaccines

Question 8

Dexamethasone

Answer 8

• Immunosuppressant
• Glucocorticoid
• IV/IM
• Horses
• Can be given w/ azathioprine, cyclophosphamide, cyclosporin, chlorambucil adjuvant agents
• Immune-mediated disease; inflam skin conditions; blood transfusion (hypersensitivity/anaphylactic) reaction
• AE: Care w/ giving for hypothalamic-pituitary-adrenal (HPA) axis, high dose may shut adrenal glands down -> dec steroid production; may antagonise effect of insulin; contradicted use alongside NSAIDs
• Contraindicated: pregnant animals, diabetes mellitus, renal insufficiency, corneal ulceration, alongside live vaccines

Question 9

Azathioprine, cyclophosphamide, cyclosporin, chlorambucil

Answer 9

• Immunosuppressants
• Co-admin w/ glucocorticoids - steroid sparing to dec steroid dose + effects
• Azathioprine - don’t give to cats
• Immune-mediated diseases e.g. IMHA

Question 10

Ciclosporin

Answer 10

• Immunosuppressive but not cytotoxic (like azathioprine and chlorambucil)
• Inhibits calcineurin -> dec signalling of inflam cytokine IL-2 and dec T-cell proliferation/activity, inhibits APC in skin, inhibits degranulation of mast cells and release histamine
• Chronic allergic dermatitis (cats); atopic dermatitis (dogs)
• Give 2 h prior / after food to prevent fast absorption w/ food
• AE: Well-tolerated + uncommon in dogs; cats = common: GI signs (V+/D+/anorexia/hypersalivation), lethargy, weight loss, lymphopoenia
• Plasma conc lowered by anticonvulsants + some ABs; drugs that inhibit/induce cytochrome p450 interfere w/ conc; use w/ aminoglycoside AB/trimethoprim -> inc nephrotoxicity
• Contraindicated: Hx of malignant disorders, live vaccination (2 w before/after); diabetic dogs, w/ other immunosuppressive agents; dogs <6 m, cats w/ FeLV or FIV

Question 11

Apoquel (oclacitinib)

Answer 11

• Immunosuppressant
• Janus kinase (JAK) inhibitor
• Inhbits func of cytokines dependent on JAK enzyme activity - esp. IL-31
• Dogs: pruritus, atopic dermatitis

Question 12

Cytopoint (Lokivetmab)

Answer 12

• Immunosuppressant
• Caninised monoclonal antibody (mAb), targets canine interleukin-31
• Dogs: pruritus, atopic dermatitis
• Alternative to Apoquel

Question 13

Azathioprine

Answer 13

• Immunosuppressant
• Cytotoxic - inhibits purine synthesis -> impacts DNA & RNA synthesis; inhibits clonal proliferation during induction phase of immune response (cell- and antibody-mediated)
• AE: BM suppression; GI upset/anorexia, poor hair growth, acute pancreatitis, hepatotoxicity; caution use in renal impairment/hepatic disease
• Not recommended for cats - low in enzyme which metabolises azathioprine so prone to toxicity (fatal leukopenia/thrombocytopenia)

Question 14

Chlorambucil

Answer 14

• Immunosuppressant (not v well characterised in companion animals)
• Small cell alimentary lymphoma; IMHA
• Cytotoxic - alkylating agent which cross-links DNA during all phases of the cell cycle, impeding replication
• AE: BM suppression, anorexia, nausea, vomiting, diarrhoea, poor hair growth, neurotoxicity and seizures reported (rare)

Question 15

Cyclophosphamide

Answer 15

• Immunosuppressant
• Cytotoxic - alkylating agent which cross-links DNA during all phases of the cell cycle, impeding replication
• AE: BM suppression, V+, D+, poor hair growth, myelosuppression, inc water intake in cats to reduce risk of haemorrhagic cystitis
• Immune-mediated disease, lymphoma, various cancers

Question 16

Chlorphenamine

Answer 16

• Antihistamine
• Anaphylactic (hypersensitive) blood transfusion reaction

Question 17

Whole blood (fresh/stored)

Answer 17

• Has everything: platelets, all factors
• Fresh life = 4 h
• Stored = 28 d

Question 18

Packed RBCs

Answer 18

• Only for anaemia
• No clotting factors
• Shelf life = 42 d

Question 19

Fresh frozen plasma (FFP)

Answer 19

• All factors: fibrinogen (I), II, V, VII, VIII, IX, XI, vWF
• All coagulopathies: vit K deficiency e.g. rodenticide toxicity; vWD (suspected/confirmed); haemophilia A (VIII) + B (IX); lungworm coagulopathy; factor consumption/poor production (e.g. excessive haemorrhage, liver disease)
• Shelf life = 1 yr (18 degrees celsius), thaw prior, 5 - 30 mL/kg
• Initial transfusion rate 0.5 - 1.0 mL/kg/h for 20 - 30 min if no reaction, continue for 4 h

Question 20

Frozen plasma

Answer 20

• II, VII, IX, X, XI, variable others
• Haemophilia B (IX); vit K deficiency
• Shelf life = 5 y
• 10 - 30 mL/kg

Question 21

Cryoprecipitate

Answer 21

• I, VIII, vWF
• vWD; haemophilia A
• 6 mL/kg

Question 22

Cryosupernatant

Answer 22

• II, VII, IX, X
• Vit K deficiency; haemophilia B

Question 23

Tranexamic acid

Answer 23

• Prevents plasminogen activation, dec fibrinolysis + inc clot strength
• Hyperfibrinolysis in greyhounds, used before Sx procedures

Question 24

Chlorphenamine

Answer 24

• Antihistamine
• Blood transfusion (hypersensitivity/anaphylactic) reaction

Question 25

Imidocarb diproprionate (Imizol)

Answer 25

• Babesiosis (Babesia divergens) + tick control (lower dose)
• Ruminants
• Long withdrawal periods for meat (1/2 year)
• Only licensed Tx

Question 26

Hydroxycarbamide + hydroxyurea

Answer 26

• Chemo -> dec WBC count
• Hydroxyurea = reversible myelosuppression in in polycythaemia vera
• Chronic myeloid leukaemia (CML) (non-lymphoid leukaemia)

Question 27

Melphalan + prednisolone

Answer 27

• Chemo
• Multiple myeloma
• Dogs + cats