Pharmacology of cancer drugs Flashcards
What is potency?
Refers to the amount of a drug required to produce an effect?
What is EC50?
The concentration of drug that gives a half maximal response. The lower the EC50, the more potent the drug.
What is efficacy?
A drugs capacity to produce an effect.
What is Emax
The maximal drug effect at high drug concentrations. The higher the Emax, the higher the efficacy of the drug.
What is drug effectiveness? Is it different to efficacy?
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.
What does this graph show?
Drug specificity, curve on the left hand side is selective for that receptor at a lower concentration of the drug.
What is ED50
Median effective dose - therapeutic effect in 50% of patients
What is TD50
Median toxic dose
What is LD50 and when is it used
Median lethal dose - used when calculating the therapeutic index in animal models.
What is the therapeutic index in humans
TD50/ED50
What is the therapeutic index for a safe drug Vs a toxic drug?
Safe drug has a large TI which represents a large difference between the toxic dose and the therapeutic dose.
What is on target toxicity>
Drug interactions with the correct target that induce toxicity
What is off target toxicity>
Toxicity due to an unintended target
What is a feature of the immune response to drugs?
It is idiosyncratic - hard to predict
What are two ways that drugs can target cells
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
How does Asparginase work in the treatment of ALL
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.
What is the problem with most current cancer drugs>
They target highly proliferative cells. So their is a large amount of toxicity in normal proliferating cells around the body.
What is used to shorten the period of leukopenia due to chemotherapy?
G-CSF - initiates the active production of granulocytes and whit blood cells and their release into the blood stream
What is a flaw in drugs targeting proliferative cells (not toxicity)
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.
What’s the relationship between the number of tumor cells and the percentage of dividing cells in that tumour?
As the number of cells in the tumor increases, the number of cells that are actively dividing decreases.
Give one example of how tumour lysis syndrome can cause death
ACcumulation of potassium can disrupt cardiac muscle depolarisation which can cause sudden death.
What is the Goldie-Coldman hypothesis
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.
How can the effect of a drug combination differ?
The relationship between the two drugs can be synergistic, additive, antagonistic or suppresive.
what are the five general rules of combination therapy?
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.
