The billion dollar pill

Question 1

What are agonist drugs?

Answer 1

Drugs that stimulate biological responses

Question 2

What are antagonist drugs?

Answer 2

Drugs that inhibit biological responses.

Question 3

What are the 3 tenets of pharmaceutical science?

Answer 3

1. All drugs must bind to a biological target in order to achieve a desired biological effect.
2. Magnitude of the response depends on the dose.
3. Every drug is a potential poison.

Question 4

What are the general biological targets of a drug?

Answer 4

1. Targets that are overexpressed.
2. Targets that are underexpressed.
3. Targets that control a critical process that affects the biology that you are trying to manipulate.

Question 5

What is the largest class of drug targets?

Answer 5

Enzymes.

Question 6

What are exogenous molecules?

Answer 6

Molecules originating from outside the organism

Question 7

What is pharmacokinetics and pharmacodynamics?

Answer 7

pharmacokinetics: study of how the body affects the drug
Pharmacodynamics: study of how the drug affects the body

Question 8

Where are HER2 receptors overexpressed?

Answer 8

on the cell surface of breast tumours

Question 9

Why are enzymes the largest class of drug targets?

Answer 9

because of the presence of the active site, which can be exploited as binding sites for pharmaceutical enzyme inhibitors

Question 10

How does potency relate to EC50?

Answer 10

higher potency = lower EC50

Question 11

Why is higher potency of a drug sometimes bad?

Answer 11

the chance of the drug binding to other targets is higher, causing side effects

Question 12

What are the 2 ways in which a drug can become a poison?

Answer 12

1. Too much action on the target
2. Loss of selectivity, where the drug binds to other targets

Question 13

What is the first step in the process of drug discovery?

Answer 13

Identification and validation of a target.

Question 14

What are the criteria for a good target?

Answer 14

1. The target’s 3D structure is accessible
2. Effects of altering the target is measurable
3. It is not evenly distributed throughout the body

Question 15

What are the criteria during target validation?

Answer 15

1. Is the effect of the target reproducible?
2. Can the target be modulated?

Question 16

After identifying a target, how is the drug chosen?

Answer 16

Start with a endogenous molecule that is known to bind to the target and go from there

Question 17

What is an endogenous molecule?

Answer 17

A molecule originating from inside the organism

Question 18

What is a pharmacological assay?

Answer 18

An investigative procedure to measure the presence, amount or functional activity of a drug

Question 19

What are the 4 processes of pharmacokinetics?

Answer 19

1. Absorption
2. Distribution
3. Metabolism
4. Elimination

Question 20

Why might drugs not be absorbed into the bloodstream?

Answer 20

1. poor solubility
2. degradation prior to absorption
3. cannot be transported well across the cellular barrier

Question 21

What is paracellular transport?

Answer 21

Transport of molecules in between 2 cells

Question 22

How do you use logP to determine hydrophobicity?

Answer 22

1. Negative log P = hydrophilic
2. Positive log P = hydrophobic

Question 23

Why are some drugs taken with food or milk?

Answer 23

1. They are poorly soluble in water, so the food/milk allows the drug to be absorbed into the bloodstream
2. To delay the absorption of some drugs

Question 24

What is the bioavailability of a drug administered through IV injection? Why?

Answer 24

1
because there is no pre-absorption losses

Question 25

What is the first pass effect?

Answer 25

A phenomenon in which a drug gets metabolised at a specific location in the body that results in a reduced concentration of the active drug upon reaching its site of action or the blood.

Question 26

Why are some drugs taken before meal?

Answer 26

1. Food may inhibit metabolism of the drug 2. Speeds up gastric emptying so there's quicker exposure to the drug

Question 27

What is the most water soluble area of the body?

Answer 27

Blood

Question 28

What is the most lipid soluble area of the body?

Answer 28

bone marrow

Question 29

What does volume of distribution measure?

Answer 29

It approximates how well a drug binds to different tissues

Question 30

What are instances where a drug's poor oral absorption is a good thing?

Answer 30

Poor absorption means the drug will stay in the gut longer, which is good if you want a localised effect in the gut

Question 31

What is the goal of metabolism?

Answer 31

1. To convert a foreign substance into a more water soluble entity so that it can be readily excreted from the system 2. To convert a substance into something less reactive so that it causes less harm to the system

Question 32

What happens if the metabolism of a drug is too fast or too slow?

Answer 32

1. Too fast: The effect of the drug may be too little 2. Too slow: The effect of the drug may become toxic

Question 33

What is biotransformation?

Answer 33

Chemical modification of the compound made by an organism usually through an enzymatic process

Question 34

What are xenobiotics?

Answer 34

Chemicals found in the body which are not normally produced or present within the organism

Question 35

What is bioactivation?

Answer 35

Enzymatic conversion of a substance into a reactive species

Question 36

What are the general characteristics of metabolism?

Answer 36

1. It is an enzymatic process 2. One enzyme can metabolise many subtrates 3. Targets are mostly xenobiotics 4. They exhibit genetic differences

Question 37

What are some organs that carry out metabolism?

Answer 37

1. liver 2. kidneys 3. gastrointestinal mucosa 4. skin 5. lung

Question 38

What is the primary organ for metabolism?

Answer 38

Liver

Question 39

How are water soluble substances secreted?

Answer 39

Secreted by the kidneys in urine

Question 40

How are fat soluble substances secreted?

Answer 40

Secreted by liver into bile and then in faeces

Question 41

What is clearance?

Answer 41

It reflects the intrinsic ability of the body to clear the specific drug

Question 42

What is the main organ that eliminates drugs from the body?

Answer 42

Kidney

Question 43

What is enterohepatic recirculation and how is it significant?

Answer 43

1. It is the process by which bile gets reabsorbed back into the blood from the small intestine 2. It prolongs the half life of the drug

Question 44

What is bioavailability?

Answer 44

It provides an indication of the proportion of the administered dose that will be taken into the circulatory system.

Question 45

What are the main categories of toxicity testing?

Answer 45

1. general toxicity 2. safety pharmacology 3. developmental and reproductive toxicity 4. immunotoxicity 5. phototoxicity 6. genotoxicity and carcinogenecity

Question 46

What are the limitations of toxicity testing?

Answer 46

1. Many toxicities are hard to pick up from trials 2. We do not fully understand the mechanism of toxicities 3. All models are imperfect (computer based, animal models, human studies)