Pharmacology of cancer drugs

Question 1

What is potency?

Answer 1

Refers to the amount of a drug required to produce an effect?

Question 2

What is EC50?

Answer 2

The concentration of drug that gives a half maximal response. The lower the EC50, the more potent the drug.

Question 3

What is efficacy?

Answer 3

A drugs capacity to produce an effect.

Question 4

What is Emax

Answer 4

The maximal drug effect at high drug concentrations. The higher the Emax, the higher the efficacy of the drug.

Question 5

What is drug effectiveness? Is it different to efficacy?

Answer 5

Differs to efficacy because it relates to the drugs efficacy in real world use. Achieves this by taking safety profile of the drug into account.

Question 6

What does this graph show?

Answer 6

Drug specificity, curve on the left hand side is selective for that receptor at a lower concentration of the drug.

Question 7

What is ED₅₀

Answer 7

Median effective dose - therapeutic effect in 50% of patients

Question 8

What is TD₅₀

Answer 8

Median toxic dose

Question 9

What is LD₅₀ and when is it used

Answer 9

Median lethal dose - used when calculating the therapeutic index in animal models.

Question 10

What is the therapeutic index in humans

Answer 10

TD₅₀/ED₅₀

Question 11

What is the therapeutic index for a safe drug Vs a toxic drug?

Answer 11

Safe drug has a large TI which represents a large difference between the toxic dose and the therapeutic dose.

Question 12

What is on target toxicity>

Answer 12

Drug interactions with the correct target that induce toxicity

Question 13

What is off target toxicity>

Answer 13

Toxicity due to an unintended target

Question 14

What is a feature of the immune response to drugs?

Answer 14

It is idiosyncratic - hard to predict

Question 15

What are two ways that drugs can target cells

Answer 15

1 - targeting differences between normal and cancer cells on the phenotypic level e.g proliferation, differentiation, invasiveness and metastasis

2- Targeting the host biochemical pathways e.g angiogenesis, immune system, inflammation

Question 16

How does Asparginase work in the treatment of ALL

Answer 16

Normal cells have an intrinsic machinery that is capable of producing L-asparagine for the subsequent production of cellular proteins. Lymphoblasts however do not have this intrinsic machinery so are entirely dependent on the L-asparagine derived from serum. Asparaginase function is to metabolise serum L-asparagine into L-aspartic acid, starving lymphoblastic cells of L-asparagine and preventing their ability to form cellular proteins, leading to their death.

Question 17

What is the problem with most current cancer drugs>

Answer 17

They target highly proliferative cells. So their is a large amount of toxicity in normal proliferating cells around the body.

Question 18

What is used to shorten the period of leukopenia due to chemotherapy?

Answer 18

G-CSF - initiates the active production of granulocytes and whit blood cells and their release into the blood stream

Question 19

What is a flaw in drugs targeting proliferative cells (not toxicity)

Answer 19

They depend on cells being in a specific stage of the cell cycle. A number of tumour cells are found to be quiescent, and are not actively targeted by the drug. Subsequently these cells are able to re-enter into a proliferative state and cause relapse.

Question 20

What’s the relationship between the number of tumor cells and the percentage of dividing cells in that tumour?

Answer 20

As the number of cells in the tumor increases, the number of cells that are actively dividing decreases.

Question 21

Give one example of how tumour lysis syndrome can cause death

Answer 21

ACcumulation of potassium can disrupt cardiac muscle depolarisation which can cause sudden death.

Question 22

What is the Goldie-Coldman hypothesis

Answer 22

Drug resistance occurs due to spontaneous mutations and is a consequence of cancer cell proliferation. A resistant cell appears in every 100,000. Therefore in a 1g tumour made up of 10⁹ cells, there would be 10⁴ resistant clones. If adjuvant therapy was used, less than one cell will be resistant.

Question 23

How can the effect of a drug combination differ?

Answer 23

The relationship between the two drugs can be synergistic, additive, antagonistic or suppresive.

Question 24

what are the five general rules of combination therapy?

Answer 24

1 - Individual drugs must be active against the tumour.

2 - Drugs must have different modes of action to minimise drug resistance

3 - Drugs must not have overlapping toxicities.

4 - Drug additive, synergistic, antagonistic effects musr have been investigated

5 - Individuals should be optimally scheduled.