Chemical Pharmacology

Question 1

How can the solubility of benzoic acid can be improved?

Answer 1

By forming a sodium salt

Question 2

How can hydrophobic drugs be dissolved?

Answer 2

Can be dissolved in another biologically compatible solvent

Question 3

Give an example of a solvent used to dissolve hydrophobic drugs

Answer 3

Ethanol

Question 4

What makes a compound chiral?

Answer 4

If it is non-superimposable on its mirror image

Question 5

What is an achiral compound?

Answer 5

A compound which can be superimposed on their mirror image

Question 6

How are the CIP rules imposed?

Answer 6

1. Each of the 4 groups about the chiral centre is given a priority
2. Group with the lowest priority is rotated so it points away and the 3 remaining groups are considered
3. The order of A-C is used to determine if a compound is R or S

Question 7

If the order of A-C occurs clockwise what term is used?

Answer 7

R

Question 8

If the order of A-C occurs anti-clockwise what term is used?

Answer 8

S (sinister)

Question 9

Are entaniomers chemically identical?

Answer 9

Yes, except for the way they interact with other chiral molecules

Question 10

What is a diastereoisomer?

Answer 10

Stereoisomers which are not mirror images of each other

Question 11

Generally how is the theoretical maximum of stereoisomers for a compound calculated?

Answer 11

2ⁿ where n equals the number of stereogenic centres

Question 12

What is a meso compound?

Answer 12

An achiral member of a set of diastereoisomers which will have stereogenic centres but will also have an internal plane of symmetry which renders it non-chiral

Question 13

Give a theory for how proteins discriminate between stereoisomers

Answer 13

3 point attachment theory

Question 14

What is a eutomer?

Answer 14

The enantiomer for a chiral drug which exhibits the desired biological effect

Question 15

What is a distomer?

Answer 15

The enantiomer for a chiral drug which does not exhibit the desired biological effect

Question 16

What is the eudismic ratio?

Answer 16

The ratio of the desired biological activity of the eutomer to that of the disotomer

Question 17

Outline the entantiomeric effects of ibuprofen

Answer 17

• R weakly inhibits COX-1
• S equally inhibits COX-1 and COX-2
• Administering the distomer contributes to the therapeutic effect of the drug

Question 18

What is a racemate/racemic mixture?

Answer 18

Equal amounts of left and right handed enantiomers

Question 19

Are entaniomers physically identical?

Answer 19

Yes except for the way they interfer with plane polarised light

Question 20

Give an example of a drug where administering a racemate increases selectivity for the drug target

Answer 20

• Dobutamine is used to treat heart failure
• • dobutamine is an α1 and β1 agonist
• -dobutamine α1 antagonist and β1 agonist
• Racemate increases selectivity for β1 adrenoceptors

Question 21

What is the partition coefficient?

Answer 21

A measure of how hydrophilic/hydrophobic a substance is

Question 22

How is the partition coefficient measured?

Answer 22

The substance (in this case drug) is added to a mixture of an organic solvent and water and shaken, the concentrations of drug in each of these solvents is then measured

Question 23

What is the calculation for partition coefficient?

Answer 23

[compound] n-octanol/[compound] in water

Question 24

Does a high log(P)/ a high log (partition coefficient) mean a compound is lipophilic?

Answer 24

Yes

Question 25

What is the optimum logP value for a drug? Why?

Answer 25

* Around 2 * It allows drugs to both enter and leave the phospholipid bilayer

Question 26

What is the mechanism for action of local anaesthetics? How does ionization affect this?

Answer 26

* contain basic amine group * block Na+ ion channels within nerve cells * to bind in the ion channel they must be ionized * to be carried across the membrane into the nerve cell they must be in their unionized form

Question 27

How do mustard gases cause damage?

Answer 27

* Mustard gas covalently bonds to DNA base pairs * Crosslink 2 opposing DNA strands which causes a structural change to DNA * If the cell cannot repair the DNA apoptosis occurs

Question 28

Give 2 examples of less toxic alkylating agents

Answer 28

* cisplatin * cyclophosphamide

Question 29

What are the problems with modern alkylating agents?

Answer 29

* They are somewhat unselective * They react with DNA base pairs where ever they encouter them * The only discriminate based on how fast the cells are dividing

Question 30

Give an example of a drug which works by DNA intercalation

Answer 30

Doxorubicin which treats cancer cells

Question 31

How does Doxorubicin work?

Answer 31

* Very planar and so it is able to slide between parallel base pairs of DNA helix * This causes distortion which blocks the normal function of enzyme topoisomerase 2 * Prevents DNA replication

Question 32

What is an advantage for DNA groove binding drugs?

Answer 32

Can potenially be selective for DNA sequences

Question 33

Give an example of a DNA groove binding drug

Answer 33

Netropsin binds in the minor groove and has some selectivity for AT sequences