PA30325 2. Medicines Design

Question 1

What are the Pro-drugs and Soft-drugs?

Answer 1

Pro-drugs
- compounds that are inactive until activated by metabolism

Soft-drugs
- active species that are deactivated by metabolism

Question 2

Why do we use soft-drugs?

Answer 2

• to reduce duration of action
• to reduce side effects/toxicity by limiting how broadly distributed the drug is
• by having predictable metabolism to inactive species you reduce the risk of metabolism leading to multiple metabolites with varying biological activities

Question 3

What are the ideal soft-drugs compounds?

Answer 3

• cannot modify the known active molecule too much, or you risk losing activity
• introduction of the metabolically sensitive group should not overly change the physical, steric and electronic properties of the lead
• ideally looking for a metabolisable isostere (similar shape and often electronic properties)
• most often used are esters, carbamates, and less often quaternary nitrogens

Question 4

Describe local anaesthetic action

Answer 4

• reversible binding to, and inactivation of, sodium ion channels
• highest affinity for the open state of the channel

Question 5

How do sedative-hypnotics act?

Answer 5

• act by enhancing the inhibitory actions of GABA.a receptors