Anti-cancer drugs

Question 1

What is the mechanism of action of alkylating agents?

Answer 1

Insert alkyl group, usually a carbonium ion, that cross-links adjacent bases in DNA, particularly G, as well as proteins. This causes stress, breaking the strand and resulting in apoptosis. Cycle non-specific. Cross-linking between strands is more desirable.

Question 2

List four groups of classic cytotoxic agents.

Answer 2

Alkylating agents
Antimetabolites
Plant alkaloids
Hormonal agents antagonists

Question 3

List two types of novel anticancer agents.

Answer 3

Monoclonal antibodies

Immunomodulating agents

Question 4

List types of supportive therapy.

Answer 4

Analgesics, antidepressants, diet.

Question 5

What is the mechanism of action of antimetabolites?

Answer 5

Block DNA synthesis by substituting nucleotides. S phase inhibitors.

Question 6

List three targets of antimetabolites.

Answer 6

Folate, pyrimidine bases (C, T), purine bases (A, G)

Question 7

What is the mechanism of action of plant alkaloids/mitotic poisons?

Answer 7

Inhibit either microtubule function or topoisomerase. M phase inhibitors.

Question 8

List two hormone modulators used in breast cancer.

Answer 8

SERMS and aromatase inhibitors (inhibit oestrogen release from adipocytes)

Question 9

List two hormone modulators used in prostate cancer.

Answer 9

Anti-androgens, gonadotrophin-RH analogues (reduce endogenous LH release )

Question 10

Which hormone modulators are used for blood-borne cancers?

Answer 10

Glucocorticoids

Question 11

What are common adverse effects of classic cytotoxic agents?

Answer 11

Alopecia, skin blistering and necrosis, GI sores (stomatitis) and mouth inflammation (mucositis), nausea and vomiting (chemo-trigger zone), infertility (particularly sperm), bone marrow suppression, organ toxicity.

Question 12

Which organs are affected by organ toxicity of classic cytotoxic agents?

Answer 12

Heart - dysrhythmia, altered contractility, acute-chronic heart failure
Nervous system - targeting microtubules affects axonal transport
Kidneys - renal failure
Urinary bladder - haemorrhagic cyctitis

Question 13

List three drug groups used to manage ADRs of classic cytotoxic drugs?

Answer 13

Antiemetic drugs
Colony stimulating factor (replenishing blood cells)
Organ toxicity drugs for haemorrhagic cystitis

Question 14

Which antiemetic drugs are used in managing ADRs of classic cytotoxic agents?

Answer 14

Dopamine recetor antagonist (metoclopramide)
Serotonin receptor antagonist (ondansetron) - best
Neurokinin (substance p) receptor antagonist (aprepitant)
Glucocorticoids (dexamethasone)

Question 15

Which colony stimulating factors are used in managing ADRs of classic cytotoxic agents?

Answer 15

Filigrastim (WBCs, particularly neutrophils)

Erythropoietin (RBCs)

Question 16

When is mesna used in managing ADRs of classic cytotoxic agents?

Answer 16

When alkylating agents are used to reduce haemorrhagic cyctitis without affecting therapy.

Question 17

List 5 types of novel anti-cancer agents.

Answer 17

Monoclonal antibodies
Immunomodulating agents (biological response modifiers, cytokine treatment)
Inhibitors of intracellular signalling molecules (tyrosine kinase inhibitors, serine-threonine kinase inhibitors)
Sensitising agents

Question 18

List two monoclonal antibody drugs and their mechanism of action.

Answer 18

Rutiximab - anti-CD20 when over-expressed on B cells in non-Hodgkin’s lymphoma, triggering B cell lysis.

Trastuzumab (Herceptin) - binds to human epidermal growth factor 2 (HER2) when over-expressed in breast cancer

Attachment of cytotoxic agent to antibody

Question 19

List two biological response modifiers and their mechanism of action.

Answer 19

Interferons - augment the cytotoxicity of immune cells to inhibit proliferation and alter antigen expression of tumour and immune cells.

IL-2 - sensitise patient’s lymphocytes in-vitro as IL-2 stimulates lymphocyte proliferation and cellular immunity, not first-line

Question 20

What is the mechanism of action of inhibitor’s of intracellular signalling molecules?

Answer 20

Bind to kinase’s ATP site

Some also inhibit angiogenesis

Question 21

When are kinase inhibitors used?

Answer 21

Selected leukaemia and GI tumours

Question 22

Give an example of an immunisation using sensitising agents.

Answer 22

BCG for TB

Question 23

List three complications of novel anti-cancer agents.

Answer 23

Drug resistance, tumour cell sanctuaries (tumour in inaccessible site), dose exhaustion.

Question 24

How can drug resistance be overcome?

Answer 24

Multiple cytotoxic drug therapy, drugs with different actions, drug holidays

Question 25

How can tumour cell sanctuaries be overcome?

Answer 25

Radiotherapy, surgery

Question 26

How can dose exhaustion be overcome?

Answer 26

Multiple drug therapy, radiotherapy, surgery, chemotherapy combination.