Brazier: Medicines for cardiovascular disease

Question 1

Describe what intramolecular bonding is?

Answer 1

Bonding within the same molecule: includes covalent bonding (hydrogen and van der waals)

Question 2

Describe what intermolecular bonding is?

Answer 2

Bonding between two neighbouring molecules: Non covalent bonding

Question 3

What are the main types of interactions?

Answer 3

1. Van der waals
2. Electrostatic
3. Hydrogen bonding
4. Dipole dipole and ion dipole
5. Repulsive forcesw

Question 4

What is the lock and key hypothesis?

Answer 4

1. Rigid structure
2. Perfect to fit active site
3. No explanation for multiple substrates

Question 5

What is Koshland’s induced fit theory?

Answer 5

1. Substrate not ideal shape
2. Active site forced to change driven by maximisation of intermolecular binding interactions so many substrates are tolerated by enzyme or receptor
3. Substrate is not passive spectator
4. Binding interaction strong enough to hold substrate but allow release of neurotransmitter

Question 6

What are the 3 main points about drug agonists that are required for them to bind to the receptor to activate it?

Answer 6

1. Drugs must have correct binding groups
2. Binding groups must be in correct position
3. Drug must be correct size for binding site

Question 7

Why would you give a patient salbutamol to relieve the symptom of bronchospasm due to an overdose of atenolol?

Answer 7

• Atenolol is an antagonist for the Beta adrenergic receptors
• Whilst salbutamol is a beta 2 receptor agonist
• Bronchospasms are a result due to atenolol’s excessive action on both beta 1 and beta 2 receptors
• Adding an agonist will return normal levels of activity

Question 8

What is the main group in the beta 1 and beta 2 active sites that are different to each other?

Answer 8

Amino acids- can allow for selective binding due to benzene ring and square

Question 9

What can the rotation of an amino acid group do in a drug molecule?

Answer 9

Open up additional extra binding regions in the active site

Question 10

Ramipril is a prodrug, what is it converted to in the body as a result of metabolism?

Answer 10

Carboxylic acid

Question 11

Why do we administer Ramipril and Ramiprilat?

Answer 11

1. Low oral bioavailability of ramiprilat due to two carboxylic acid groups
2. Too polar to diffuse across the cell membrane in its small intestine