My q's: antineoplastic meds and chemo

Question 1

use of the drugs and tumours

Answer 1

they work very well in rapidly dividing tumours due to being so potent

• require several cycles of chemotherapy in order to work
• oral or injectables usually
• routes of administration: IV, SC, IM, oral, topical
• split into further groups due to their MOA

Question 2

how do cytotoxic drugs work best?

Answer 2

• in the pre-clinical growth phase
• where’s past this phase there’s far too many cells to kill
• cytotoxic drugs can be cell cycle specific including G1 phase, S phase, G2, M and G0 phase

Question 3

1st group: alkylating agents

Answer 3

• inhibit replication of DNA, labels the DNA and increases the breakdown of molecules
• alkylation of RNA and proteins too
• non cell cycle specific

CYCLOPHOSPHAMIDE: most common, side effects in the bladder
- oral and IV
CHLORAMBACIL: best absorbed orally, slow acting, can cause haemorrhagic cystitis esp if treated with cyclophosphamide

Question 4

2nd group: platinating medicine

Answer 4

• bifunctional alkylating
• inter and intra-strand cross-link in DNA
• non specific to the cell cycle

CISPLATIN & CARBOPLATIN are the 2 most common drugs in this group

Question 5

3rd group: antimetabolites

Answer 5

• analogs (similar structures to) the molecules pyrimidine, purine & folic acid
• incorporated into RNA and DNA to impair DNA synthesis
• S phase specific

5-FLUROACIL: inhibits the enzyme Thymidylate synthase
METHOTREXATE: inhibits Dihydrofolate reductase
CYTOSINE ARABINOSIDE

Question 6

4th group: mitotic spindle inhibitors

Answer 6

• cell division by binding to tubulin
• active at G2 and M phases

VINCRISTINE
VINBLASTINE
PACLITAXEL

Question 7

5th group: topoisomerase inhibitors

Answer 7

• inhibit topoisomerase II by unwindng and rejoining DNA
• non specific to cell cycle but not active in S phase

ACTINOMYCIN: deactivates T cells and antibody production
L-ASPARAGINASE: doesn’t cause the common side effect myelosuppression
PIROXICAM: inhibits COX2 activity

Question 8

clinical uses of cytotoxic meds

Answer 8

• dose dependent on body surface area (BSA) NOT body weight like most drugs
• DONT use in pregnant animals
• not effective in the G0 phase when cells are resting
• drug resistance can develop in neoplastic cells
• can combine with other drugs to minimise risk of resistance
• resistance can be intrinsic (nautrally resistant) or acquired (occurs overtime)

Question 9

side effects

Answer 9

• pulmonary toxicity
• neurotoxicity
• cardiomyopothy toxicity (definitely from doxorubicin - doesn’t cross blood brain barrier so dont use for brain tumour)
• DONT use cisplatin in cats and 5-fluroacil

Question 10

what’s used for what cancers?

Answer 10

bladder cancer: Peroxicam

Mast cell tumour: Toceranib & Mastinib
for dogs use vincristine

Lymphoma: cyclophosphamide, vincristine, doxorubicin

osteosarcoma: Doxorubicin and sometimes platinating agents

Question 11

different regimes: one drug or multiple

Answer 11

Monotherapy = one drug used for chemotherapy

if multiple drugs are being used, it’s based on whether the cancer is localised or widely distributed around the body. also have to consider if theres risk of reoccurance.

Question 12

important random notes

Answer 12

• cyclophosphamide is an immunosuppressant (more prone to infections)
• cisplatin & fluorouracil cant be used in cats
• vincristine can cause skin necrosis and irritation

Question 13

how can resistance occur

Answer 13

• cancer cells develop better DNA repair mechanism
• altered/changed metabolism of cytotoxic meds

the 3 main factors that contribute to it are:

1. kinetic (tumour growth)
2. biochemical
3. pharmacological