Chemotherapy

Question 1

What is cancer?

Answer 1

Continuous uncontrolled growth of cell

Tumour - abnormal proliferation of cells

Question 2

Difference between benign and malignant tumour?

Answer 2

Benign - confined to original location

Malignant - capable of invading surrounding tissue and metastasising

Question 3

Cause cancer?

Answer 3

VOTE

Virus, oncogenes, tumour suppressor gene, environmental exposure

Question 4

Difference between primary, neoadjuvant and adjuvant chemotherapy?

Answer 4

Primary - pt w/ advanced cancer - no alternative tx
Neoadjunctive - pt w/ localised cancer
Adjunctive - combined other therapies

Question 5

Main goal of agents used in chemotherapy and problems face?

Answer 5

Eliminate cancer cells w/o affecting normal cells

All cytotoxic drugs affect normal tissue - therefore aim therapeutic index

Question 6

What is therapeutic index?

Answer 6

LD50/ED50
LD50 = lethal dose of drug for 50% population
ED50 = minimum effective dose for 50% population

Question 7

Long-kill hypothesis?

Answer 7

Chemotherapeutic agents kill constant proportion of cell population not constant number of cell

Question 8

CCS/ vs CCNS drugs?

Answer 8

CCS = cell cycle specific - exert action on cell cycle e.g anti-metabolites/ taxanes

CCNS - cell cycle non-specific - sterilise tumour where they are cyclin or resting in G0 e.g ankylating agents/ anti tumour abs

Question 9

What are ankylating agents and what is their mechanism?

Answer 9

CCNS
Form highly reaction carbonic ion - transfer alkyl group to nucleophilic site on DNA base - cause abnormal base pairing and DNA strand breakage

Question 10

Side effect anklyating agents?

Answer 10

Carcinogenic - increase risk of secondary malignancy

Immunosuppressant action

Question 11

Examples of ankylating agents?

Answer 11

1. Busulfan
2. Lomustine
3. Decarbazine

Question 12

Resistance and ankylating agents?

Answer 12

Increase activity DNA repair enzyme

Increased metabolic inactivation of drug

Question 13

What are platinum analogues and their mechanism?

Answer 13

CCNS

Form highly reactive platinum complex - DNA damage

Question 14

Example platinum analogue

Answer 14

Cisplatin - highly bound to plasma protein allow to be carried in circulation

Highly conc kidney, intestine and testes

Question 15

What are antimetabolites and how do they work?

Answer 15

CCS - act on metabolism of proliferating cells

Question 16

Example anti-metabolites?

Answer 16

1. Folate antagonist - methotrexate
2. Purine antagonist - 6 mercaptopurine
3. Pyrimidine antagonist - 5 fluorouracile

Question 17

What are vinca alkaloids?

Answer 17

CCS
Natural production derived from periwinkle
Act by inhibiting tubulin proliferation - disrupt assembly microtubules = mitotic arrest in metaphase

Question 18

What are taxanes and their mechanism?

Answer 18

CCS

Alkaloid ester - enhance tubulin polymerisation - promote microtubule assembly in absence proteins = inhibition mitosis

Question 19

Example taxanes?

Answer 19

Paclitaxel

Question 20

How to antitumoir ab work?

Answer 20

Bind to DNA blocking synthesis and interfere w/ cell replication

Question 21

Example anti-tumour ab?

Answer 21

1. Doxorubicin
2. Mtiomiycin - CCNS
3. Bleomycin - CCS

Question 22

Name 3 examples of hormones and antagonists used in cancer?

Answer 22

1. Glucocorticoids
2. Oestrogen - antagonist androgens
3. Oestrogen antagonist - breast cancer

Question 23

Bone metastases cause?

Answer 23

Spread to bone” pain, hypercalcemia, anaemia, increased risk infection

Cause: decreased mobility, skeletal fractures

Question 24

Disadv bisphosphoantes

Answer 24

1. Only 50% taken up by skeleton - rest excreted kidney
2. Poor oral bioavailability
3. Bind Ca diet - cause GI symptoms - nausea, vomit, indigestion, diarrhoea

Question 25

What are drug combinations based on?

Answer 25

1. Efficacy
2. Toxicity
3. Optimum schedule
4. Mechanism of interaction

Provide maximal cell kill within range of toxicity