Chemotherapy and immunosuppressive drugs

Question 1

Cyclophosamide

Answer 1

• nitrogen mustard drug (Alkylate agent)
• most potent within this class
• used for carcinomas, sarcomas, feline lymphoproliferative disease, mammary carcinoma and lymphomas
• multiple side effects (list some)
• has to be metabolized

Question 2

Chlorambucil

Answer 2

• nitrogen mustard drug (Alkylate agent)
• less potent, less toxic to urinary bladder and doesn’t need biotranformation to become active
• immunosuppressant for cats
• may cause alopecia, nausea and vomiting
• more toxic if also using prednisone or phenobabital

Question 3

Melphalan

Answer 3

• nitrogen mustard drug (Alkylate agent)
• used for plasma cell tumours
• more toxic to bone marrow
• repeat every 3 weeks

Question 4

Nitrosoureas

Answer 4

• alkylate agent
• needs metabolic transformation to become active
• biggest toxicity affect is with bone marrow and may not spare stem cells
• lipid soluble so about to cross BBB and be use to treat CNS tumours!!
• toxicity might not be seen until 4-5wks after treatment and then recovery may not be until 42d after that
• tx: lymphosarcomas and malignant melanomas

Question 5

Cisplatin (Platinol)

Answer 5

• crosslinks around platinum ions instead of alkyl groups
• treatment for solid tumours like mast cell tumours, osteosarcomas
• DONT USE IN CATS
• causes nephrotoxicity so have to give fluids before

Question 6

Carboplatin

Answer 6

• better used in cats then Cisplatin
• second generation platinum derivative
• less nephrotoxic and ototoxic
• thrombocytopenia is dose limiting toxicity

Question 7

Methotrexate

Answer 7

• antimetabolite drug
• interferes with DNA, RNA and protein synthesis because it interferes with DHFR enzyme which is needed for purine synthesis
• adverse effects: nausea, vomiting and anorexia

Question 8

6- Mercaptopurine

Answer 8

• antimetabolite drug
• inhibits purine synthesis
• also used as an immunosuppressive drug

Question 9

5-Fluorouracil

Answer 9

• antimetabolite drug
• DONT USE IN CATS
• used topically or IV (wide tissue distribution and crosses BBB)
• interferes with thymine production
• used to treat squamous cell carcinomas in horses

Question 10

Cytarabine

Answer 10

• antimetabolite drug
• blocks DNA synthesis by inhibiting DNA polymerase
• tx: lymphoma and myelogenous leukemia
• very bone marrow suppressive, nausea and vomiting are adverse effects
• nadir: 7-14d

Question 11

Vincristine

Answer 11

• Vinca Alkaloid drug
• used to treat lymphosarcomas, transmissible venereal disease and other solid tumours
• DONT GET PERIVASCULAR because it will form blisters
• DONT GIVE TO HOMOZYGOUS ABCB-1 gene deletion dogs because FATAL
• increases the amount of normal platelets released from bone marrow because it wants it tubulin. this causes platelet shape to change and therefore there is an increased release of megakaryocytes released

Question 12

Vinblastine

Answer 12

• Vinca Alkatoid drug
• not used as often as Vincristine
• tx: lymphosarcomas or disseminated mast cell tumours
• increased risk of leukopenia

Question 13

Doxorubicin

Answer 13

• antitumor antibiotic drug
• has many severe and serious side effects including bone marrow suppression, cardiotoxicity, ABCB gene (fatal) and peivascular (necrotic tissue)
• inactivates the DNA by intercalating between the DNA bases, which blocks synthesis of RNA and proteins
• also binds to cell membrane and interferes with ion transport
• also forms oxygen free radicals

Question 14

Actinomycind

Answer 14

• antitumor antibiotic drug
• tx for lymphomas and carcinomas in DOGS
• can get non dose dependent GI toxicity

Question 15

Mitoxantrone

Answer 15

• antitumor antibiotic drug
• tx for lymphosarcomas in cats and dogs
• less potent so may be useful for rescue therapy
• adverse effects: neutropenia, vomiting, colitis

Question 16

Paclitaxel

Answer 16

• taxanes drug
• messes with the microtubules so interferes with mitosis
• approved for dogs in USA
• tx:mammary carcinomas and squamous cell carcinomas if never been treated with chemo or radiation
• neutropenia, vomiting, diarrhea, anorexia,
• check for ABCB-1 gene sensitivity

Question 17

Toceranib

Answer 17

• Tyrosine kinase inhibitor
• 1st drug approved for dogs with treatment of Patnaik grade II or III, recurrent, cutaneous mast cell tumours with or without lymph node involvement

Question 18

Piroxicam

Answer 18

• NSAID that is normally used in humans for arthritis
• has some antitumor effects on transitional epithelial cells in bladder carincomas and oral squamous cell carcinomas
• use with Misoprostol to decrease risk of gastric ulcers

Question 19

Azathioprine

Answer 19

• derivative of 6-mercaptopurine and it gets metabolized by the liver into it causing decreased T cell function
• immunosuppressant drug

Question 20

Cyclosporine

Answer 20

• treatment for IMHA and immune mediated dermatoses
• blocks T helper cell production and inhibits the production of cytokines
• very expensive and need to try 10d treatment
• immunosuppressive drug

Question 21

Leflunomide

Answer 21

• immunosuppressive drug
• tx: immune mediated and inflammatory disease of dogs that didn’t respond to conventional therapy (ex/ IMHA)
• adverse effects: decreased appetite, lethargy, mild anemia and GI hemorrhage

Question 22

Mycophenolate mofetil

Answer 22

• immunosuppressive drug
• inhibits IMPDH which is needed for the synthesis of guanosine for purines
• inhibited T and B lymphocytes so suppresses both cell mediated and humoral cell immunity
• less adverse effects than other drugs that treat IMHA