Medchem

Question 1

List the 3 structural features (SAR) of cocaine derivatives, and how they affect drug action.

Answer 1

1. Lipophilic/aromatic ring
   - Essential for LA activity
   - Greater lipophilicity –> faster permeation and onset of action
2. Intermediate chain: ester/amide + 1-3C
   - Determines stability and duration of action
   - Longer chain –> reduced activity
3. Hydrophilic portion: Secondary/tertiary amine or heterocycle
   - Drug needs to be basic and ionisable to form a cation
   - Facilitates binding to sodium channel for action
   - Lower pKa –> lower toxicity

Question 2

Describe the key structural feature of lidocaine and how it influences its anesthetic properties.

Answer 2

Amino-amide (amide in place of ester group)

Confers greater stability and resistance to hydrolysis [(C=N) is a strong bond] –> longer duration of action

Amide group also increases water solubility