Types & Origins Of Drugs

Question 1

What are the sources of lead compounds in the natural world?

Answer 1

• plantlife e.g. flowers, trees, bushes
• microorganisms e.g. bacteria, fungi
• animal life e.g. snakes, scorpions
• biochemicals e.g. hormones, neurotransmitter
• marine chemistry e.g. corals, bacteria, fish

Question 2

What are the sources of lead compounds in the synthetic world?

Answer 2

• chemical synthesis

- combinatorial synthesis

Question 3

What is the main source of lead compounds in the virtual world?

Answer 3

• computer aided drug design

Question 4

What is the active principle?

Answer 4

• a compound isolated from a natural extract
• principally responsible for the extract’s pharmacological activity
• often used as lead compound

Question 5

What are some drugs developed from venoms and toxins?

Answer 5

• teprotide - isolated from Brazilian viper- used to make captopril used to treat hypertension
• tubocurarine - from curare- lead for atracurium a neuromuscular blocker

Question 6

What are the steps involved in computer aided drug design?

Answer 6

• choose a verified biological target
• find a key metabolic or functional event for it
• determine the 3D structure of the critical point in this
• design ligands to modulate events by blocking this critical 3D site

Question 7

What is the strategy employed by structure-based drug design?

Answer 7

Carry out drug design based on the identified interactions between the lead compound and the target binding site

Question 8

What are are the main considerations when establishing test procedures?

Answer 8

• choosing the right bioassay

- test should be simple, quick, cost-efficient and relevant

Question 9

What are the two main challenges associated with establishing testing procedures?

Answer 9

• sufficient activity against the desired target

- minimal activity against any other targets to reduce off-target effect

Question 10

What are in vitro tests?

Answer 10

• tests carried out on target molecules, whole cells, isolated tissues or isolated organs

Question 11

What is in vivo testing?

Answer 11

Tests carried out on living systems such as animals are human volunteers

Question 12

What are the aims of enzyme assay?

Answer 12

• to evaluate the level of enzyme inhibition
• to evaluate the mode of inhibition e.g. competitive or non-competitive
• to measure IC50

Question 13

What are the aims of enzyme inhibition tests?

Answer 13

• identify type of inhibition i.e. competitive or non-competitive
• strength of inhibition measured as IC50

Question 14

What is IC50?

Answer 14

• corresponds to the concentration of inhibitor required to reduce enzyme activity by 50%

Question 15

Define affinity in terms of testing with receptors.

Answer 15

The strength with which compounds bind to a receptor

Question 16

Define efficacy in terms of testing with receptors.

Answer 16

A measure of the maximum biochemical effect resulting from binding of a compound to a receptor

Question 17

Define potency in terms of testing with receptors.

Answer 17

The code traction an agonist required to produce 50% of the maximum possible effect
- the smaller the does required to achieve the biological effect, the more potent the agonist

Question 18

What are some advantages associated with in vitro testing?

Answer 18

• more suitable for routine testing
• used in high throughput screening
• measures the interaction a drug with the target
• can be used to test for pharmacokinetic properties of drug candidates
• results are easier to rationalise as there are less factors involved

Question 19

What are some limitations associated with in vitro testing?

Answer 19

• does not evaluate the ability of the drug to reach the target
• does not demonstrate a physiological or clinical effect
• does not identify possible side effects
• does not identify effective prodrugs

Question 20

What are some of the advantages associated with in vivo testing?

Answer 20

• measures an observed physiological effect
• measures a drug’s ability to interact with its target
• measures a drug’s ability to react its target
• can identify possible side effects

Question 21

What is a disadvantage associated with in vivo testing?

Answer 21

• rationalising may be difficult due to the number of factors involved.

Question 22

What are three in vivo tests?

Answer 22

• using transgenic animals - genetically modified animals
• drug potency
• therapeutic ratio/ index

Question 23

What is therapeutic ratio/ index?

Answer 23

It compares the dose level of a drug required to produced a desired effect in 50% of the test sample (ED50) versus the dose level that is lethal to 50% of the sample (LD50)

Question 24

What are the main source of lead compounds?

Answer 24

• natural world
• synthetic world
• virtual world