Pharmacology P&I

Question 1

Define pharmacokinetics.

Answer 1

What your body does to the drug.

Question 2

Define pharmacodynamics

Answer 2

What the drug does to your body.

Question 3

Define bioavailability.

Answer 3

Fraction of the administered dose of the drugs that reaches systemic circulation. Expressed as F.

Question 4

What factors affect bioavailability?

Answer 4

Molecular weight of drug
gastric pH
First pass metabolism (hepatic)

Question 5

Define apparent volume of distribution.

Answer 5

total amount of drug in the body divided by drug blood plasma concentration

Question 6

Define clearance.

Answer 6

Volume of plasma cleared of drug per unit time.

Question 7

Define half-life.

Answer 7

Time required for plasma concentration of drug to decrease by half. Determined by clearance and volume of distribution.

Question 8

Define volume of distribution.

Answer 8

The volume in which the amount of drug would need to be uniformly distributed to produce observed blood concentration.

Question 9

How many half lives to reach steady state?

Answer 9

4-5 half lives.

Question 10

Define steady state.

Answer 10

The concentration of the drug in the plasma has reached a therapeutically effective level and as long as regular doses are administered to balance the amount of drug being cleared the drug will continue to be active.

Question 11

Non-linear pharmacokinetics.

Answer 11

Concentration not proportional to dose. Rate of elimination constant regardless of amount of drug administered.

Question 12

Describe non-linear pharmacokinetics.

Answer 12

Concentration not proportional to dose. Rate of elimination constant regardless of amount of drug administered.

Question 13

Can the bioavailability of drugs differ with different routes of administration?

Answer 13

Yes.

Question 14

Define loading dose.

Answer 14

A loading dose is an initial higher dose of a drug that may be given at the beginning of a course of treatment before dropping down to a lower maintenance dose. Depends on concentration you wish to achieve.

Question 15

How do you work out the time taken for a drug to reach steady state?

Answer 15

5 times the half-life.

Question 16

Define drug receptor.

Answer 16

A macromolecular component of a cell with which a drug interacts to produce a response.

Question 17

Name a common therapeutic target.

Answer 17

Enzymes.

Question 18

Name 4 different types of drug receptors.

Answer 18

Enzyme linked - multiple actions
ion channel linked - fast
G protein linked - amplifiers
Nuclear (gene linked) receptors - long lasting

Question 19

Define affinity

Answer 19

measure of propensity of a drug to bind to its receptor. Attractiveness of drug and receptor.

Question 20

Different types of bond

Answer 20

Covalent

Question 21

Efficacy

Answer 21

Ability of the bound drug to change the receptor in a way that produces an affect.

Question 22

Potency

Answer 22

Relative position of the dose effect curve along the dose axis.

Question 23

When is low potency an issue?

Answer 23

If the dose you have to give is so large its hard to administer.

Question 24

Can competitive antagonists be overcome?

Answer 24

Yes.

Question 25

What is a partial agonist?

Answer 25

Has affinity but less intrinsic activity. Bind to a receptor and stimulate a response but has less than maximal efficacy.

Question 26

Therapeutic index.

Answer 26

The higher the TI, the better the drug. Low dose to produce effect, high dose to produce death.

Question 27

Name some common drug drug interactions in the elderly.

Answer 27

Statins and erythromycin /other antibiotics.
Verapamil and beta blockers
warfarin and multiple drugs including aspirin
ACE inhibitors increase hypogylcaemic effect on sulfonylureas.

Question 28

What increases the more drugs a patient is on?

Answer 28

Risk of drug-drug interactions

Risk of poor adherance

Question 29

What are the two hallmarks of malignancy?

Answer 29

Invasion (local)

Metastasis

Question 30

Define metastasis.

Answer 30

Spread of a tumour to and growth at ectopic sites via blood, lymphatics, intra-epithelial route or transcoelomic.

Question 31

Define carcinoma. What percentage of human cancers do carcinomas make up?

Answer 31

Malignant tumour derived from epithelial cells.

80%

Question 32

Define sarcoma.

Answer 32

Malignant tumour derived from mesenchymal cells.

Question 33

Define melanoma.

Answer 33

Malignant tumour derived from neural crest cells.

Question 34

Define leukaemia.

Answer 34

Malignant tumour derived from circulating white blood cells.

Question 35

Define Lymphoma.

Answer 35

Malignant tumour derived from the lymphatic system.

Question 36

What is the ECM of epithelial tissues? What is it made up of?

Answer 36

Basement membrane.

Fibronectin, collagen 4, laminin.

Question 37

Outline the different steps of the metastatic cascade.

Answer 37

1. Local invasion
2. Neovascularisation
3. Detachment
4. Intravasation (enter into blood or lymph)
5. Transport
6. Lodgement/arrest
7. Extravasation (leaves blood/lymph at ectopic site)
8. Growth at ectopic sites

Question 38

What is the correlation between E-cadherin expression and malignancy? Explain this phenomenon.

Answer 38

Less malignant, more likely to express E-cadherin.

E-cadherin is expressed on cell surface of all epithelial cells. It binds cells together.
For cells to become malignant, E-cadherin must be disrupted.

Question 39

Describe the ways in which E-cadherin expression can be disrupted.

Answer 39

1. Exon-skipping (lacking exons that encode calcium binding domain)
2. ECD promoter methylated (inactivated)
3. Mutations in proteins that interact with ECD (beta-catenin)
4. mutations in transcription factors that regulate E-cadherin (snail, slug, twist)

Question 40

Name a specific integrin and receptor that promotes invasion and metastasis.

Answer 40

Vitronectin receptor and integrin alpha-v-beta-3.

Question 41

What effect does HGF have on epithelial cells? How does it have this effect?

Answer 41

Induces them to dissociate and scatter.

Binds to cmet (on tumour surface), increases tyrosine phosphorylation of beta-catenin, disrupting ECD-mediated adhesion.

Question 42

What kind of cells may be present in the tumour microenviroment? What may these cells secrete?

Answer 42

cancer-associated fibroblasts (CAFs)
immune cells that have infiltrated the tumour *
myofibroblasts
tumour-associated vasculature
pericytes

Growth factors, chemokines, enzymes.

Question 43

Give an example of how tumour stromal interaction lead to MMP expression.

Answer 43

Breast carcinoma cells produce transforming growth factor. This causes host stromal cells to produce the MMP stromelysin 3.

Question 44

Discuss how HIF (hypoxia-inducible factor) can cause neovascularization of a tumour. What chemotherapy drug’s mechanism of action targets this process?

Answer 44

If a tumour cell is in a place where it is hypoxic - HIF is produced, causing upregulation of VEGF, causes blood vessels to grow towards tumour.
Bevacizumab (avastin).

Question 45

What are the four steps of WBC extravasation?

Answer 45

Rolling
Activation
Adhesion
Diapedesis

Question 46

What are the principal sites of metastasis for breast cancer?

Answer 46

Bone, lungs, liver, brain

Question 47

What are the principal sites of metastasis for lung adenocarcinoma?

Answer 47

Brain, bones, adrenal gland, liver

Question 48

What are some of the different hypothesis regarding metastasis?

Answer 48

Seed and soil - ectopic sites must have a similar microenvironment to the site of the primary neoplasm.
Mechanical hypothesis - metastasis occurs purely by anatomic and mechanical routes.

Question 49

What is the 5 year survival rates like for localized, regional and metastatic disease?

Answer 49

Localized - excellent
Regional - decreased
Metastatic - poor. Fewer than 20% of patients survived after 5 years for half of the cancer sites.