option D- medicinal chemistry (D.1)

Question 1

define the lethal dose (LD50)

Answer 1

the dose of a drug that causes death in 50% of laboratory animals

Question 2

define the toxic dose (TD50)

Answer 2

the dose of a drug that causes toxicity (an unacceptable adverse effect) in 50% of patients

Question 3

define the effective dose (ED50)

Answer 3

the minimum dose of a drug that produces the desired therapeutic effect in 50% of laboratory animals or human patients

Question 4

define the therapeutic index in animal studies

Answer 4

the lethal dose of a drug for 50% of the population divided by the minimum effective dose for 50% of the population (LD50/ED50)

Question 5

define the therapeutic index in humans

Answer 5

the toxic dose of a drug for 50% of the population divided by the minimum effective dose for 50% of the population (TD50/ED50)

Question 6

the greater therapeutic index, the —– the drug

Answer 6

safer

Question 7

define the therapeutic window

Answer 7

the range of dosages between the minimum amounts of the drug that produce the desired effect and a medically unacceptable adverse effect

Question 8

where does the therapeutic window typically occur?

Answer 8

it usually opens below the ED50 (where some patients can still be provided with minimal beneficial effect) and closes below the TD50 (where only a small percentage of patients might experience significant adverse effects)

Question 9

why should animal and human tests for drugs be kept to a minimum?

Answer 9

for ethical and economic reasons

Question 10

name the 6 methods of drug administration

Answer 10

orally
rectally
parenterally
by inhalation
transdermally

Question 11

describe when and how drugs would be taken orally

Answer 11

• drugs with any polar groups are generally water soluble and can be administered orally
• ingested by mouth

Question 12

describe when and how drugs would be taken rectally

Answer 12

• some chemical compounds are unstable in the highly acidic gastric juice
• in the form of suppositories or enemas

Question 13

describe when and how drugs would be taken parenterally, and state the 3 types of administration

Answer 13

• some chemical compounds are unstable in the highly acidic gastric juice

1. injected under the skin (subcutaneous injection)
2. injected into muscle tissue (intramuscular injection)
3. injected into the bloodstream (intravenous injection)

Question 14

describe when and how drugs would be taken by inhalation

Answer 14

• some volatile or highly dispersed drugs
• breathed in through the nose and mouth

Question 15

describe when and how drugs would be taken transdermally

Answer 15

non polar compounds can be applied to the skin in the form of patches, ointments, or therapeutic baths

Question 16

what are 4 considerations of drug administration?

Answer 16

dosage, tolerance, addiction and side effects

Question 17

what is a double blind test?

Answer 17

neither the researchers directly observing the patients nor the patients themselves know who is given the real drug and who receives the placebo- this is to reduce the possibility of conscious or subconscious bias in the interpretation of the experimental results

Question 18

what is a placebo?

Answer 18

a biologically inert substance

Question 19

what is the placebo effect and what is its role in clinical trials?

Answer 19

the idea that the body can sometimes be deceived into healing itself without receiving any help in the form of medical drug

this effect must be taken into account during clinical trials, so volunteers are split into 2 groups

Question 20

describe how drugs can have side effects and what these are

Answer 20

pharmaceutical drugs interfere with biological processes so no drug is completely safe or free from non-beneficial effects on the human body.

Question 21

define drug bioavailability

Answer 21

the fraction of the administered dose that is absorbed into the bloodstream

Question 22

what 4 things affect the bioavailability of drugs (and therefore the effective and toxic doses of a drug)?

Answer 22

• solubility
• polarity
• presence of certain functional groups
• method of administration

Question 22

give an example of how functional groups affect drug bioavailability

Answer 22

polar molecules containing hydroxyl, carboxyl, and amino groups are usually soluble in water and are therefore quickly absorbed from the gastrointestinal tract into the bloodstream. However, such molecules cannot easily pass through hydrophobic cell membranes, which in many cases reduces their biological activity

Question 23

why is intravenous injection the only route of administration that results in 100% bioavailability?

Answer 23

other routes of administration decrease bioavailability due to incomplete absorption, decomposition and other factors such as physiological differences

Question 24

describe drug tolerance

Answer 24

• regular administration of certain drugs may reduce the body’s response to specific medications or classes of pharmaceutical drugs due to accelerated drug metabolism or changes in cellular functions
• drug users need progressively higher doses of the drug to obtain the desired therapeutic effect

Question 25

what effect does drug tolerance have on the therapeutic window for some patients?

Answer 25

• increased doses lead to more pronounced side effects, which may eventually become unacceptable and close the therapeutic window

Question 26

describe drug addiction

Answer 26

• the compulsive desire of a user to take a drug regardless of the health problems it might cause.
• this addiction may be purely psychological but it often involves some degree of physiological dependence that leads to withdrawal symptoms when the drug is interrupted

Question 27

describe how drugs function at the molecular level

Answer 27

they interact with the binding sites of enzymes or cellular receptors (proteins composed of 2-amino acids)

Question 28

describe a drug’s interaction with enzymes

Answer 28

by binding to enzymes most drugs act as inhibitors, reducing the activity of enzymes via competitive or non-competitive mechanisms.

Question 29

describe a drug’s interaction with cellular receptors

Answer 29

if a drug binds to a cellular receptor, the cell responds to this chemical message by altering its state or allowing specific molecules to pass through the cell membrane

Question 30

what does the type and efficiency of drug-receptor interactions depend on?

Answer 30

the chemical structures of the drug and the binding site

Question 31

what type of bonds do drug-receptor interactions involve?

Answer 31

they can involve any types of chemical bonds

Question 32

what are the two requirements for the drug and receptor to form interactions such as dipole-dipole, H, ionic bonds or London forces?

Answer 32

ideally, the functional groups of the drug and receptor should be complementary to one another and have correct orientations

Question 33

how can efficient binding still be achieved if the structures of real drugs and their target receptors/enzymes do not match exactly?

Answer 33

by slight conformational changes of both the binding site and the drug molecule (induced fit theory for enzymes)

Question 34

what can we do to change the nature and strength of binding of drugs?

Answer 34

chemical modification of certain functional groups of the drug

Question 35

what is the first step of a drug development?

Answer 35

the identification of a lead compound (also known as a new chemical entity, NCE) that shows any kind of promising activity towards a specific biological target

Question 36

describe the difference between drug discovery and drug design

Answer 36

drug discovery:
the lead compound can be isolated from natural products with known therapeutic effects or synthesised in the lab and screened against cell cultures, bacteria or animals.

drug design:
if the chemical composition and 3D structure of a biological target are known, a small molecule with a complementary structure. can be designed using computer modelling techniques. This is then synthesised, tested and adjusted

Question 37

what is the second step to drug development?

Answer 37

a series of compounds similar to the lead compound are synthesised, characterised and subjected to preclinical trials

Question 38

what happens during preclinical trials?

Answer 38

each compound is rated according to its:
- activity towards the target as well as unrelated biological targets
- chemical stability
- toxicity
- solubility in water and lipids
- preparation cost
- accessibility
- environmental impact

Question 39

if all preclinical tests are successful, what happens?

Answer 39

information about the new drug is submitted to regulatory authorities and, with their approval, the drug is tested on humans in a series of clinical trials

Question 40

describe phase I of clinical trials

Answer 40

SUBJECTS; small no of healthy volunteers
TEST RESULTS; toxicity and safety dosage (TD50), side effects

Question 41

describe phase II of clinical trials

Answer 41

SUBJECTS; small no of patients
TEST RESULTS; effectiveness and effective dosage (ED50), safety and side effects

Question 42

describe phase III of clinical trials

Answer 42

SUBJECTS; large no of patients
TEST RESULTS; comparison with other available drugs, drug compatibility, further data on effectiveness, safety and side effects

Question 43

describe phase IV of clinical trials

Answer 43

post-clinical studies, where the study of effectiveness and safety of the drug continues during the whole period of its commercial use.

long term effects and chronic toxicity of the drug can be identified, including carcinogenic properties and effects on the immune system, fertility and reproductive functions