IC11 Natural product derived drugs for Pain Management

Question 1

For better studying of this IC it is better to read the slides as there are diagrams of the compound.

Answer 1

Go to onenote

Question 2

What class of drug does cocaine belong to?

Answer 2

Tropane alkaloid

Question 3

How would you describe tropane as a structure?

Answer 3

Tropane is a fused bicyclic heterocycle, containing a basic nitrogen.

It is also an alkaloid.

Question 4

What is the MOA of cocaine?

Answer 4

Cocaine blocks Na channel and prevents generation of action potential.

Question 5

pKa of cocaine - 8.6
Physiological pH - 7.4

Cocaine is a weak base.

How does the pKa of cocaine affect permeation at physiological pH?

Answer 5

The pKa of cocaine is 1.2 greater than physiological pH. This means that it will be over 90% ionized.

This also means that there will be around 10% unionized. The unionized drug will permeate the cell membrane. The 90% charged drug will then try to restore the equilibrium.

Question 6

In general, do local anaesthetic with higher lipid solubility & lower pKa values exhibit:

1) Faster or slower onset?
2) Higher or lower toxicity?

Answer 6

Faster onset, lower toxicity

Question 7

What are the 10 ideal characteristics of a local anesthetic agent?

Answer 7

1. Reversible blockade
2. Selective for sensory neuron w no effect on motor neuron
3. Rapid onset
4. Sufficient duration of action
5. Chemically stable when sterilized
6. No systemic toxicity
7. Wide margin of safety
8. Compatible w other co-administered drugs
9. Absence of ADRs
10. Inexpensive

Question 8

Morphine is metabolised into 2 metabolites:
1. Morphine 3-O-glucuronide
2. Morphine 6-O-glucuronide

What are the 2 effects of the metabolites?

Answer 8

1. Morphine 3-O-glucuronide - antagonistic to the analgesic effects of morphine.
2. Morphine 6-O-glucuronide - more effective and longer lasting analgesic than morphine, w fewer side effects.

Question 9

What are alkaloids?

Answer 9

Alkaloids are basic compounds that contain at least 1 nitrogen atom.

Question 10

Based on cocaine’s chemical structure in this link, what are the functional groups present in cocaine?

https://pubchem.ncbi.nlm.nih.gov/image/imgsrv.fcgi?cid=446220&t=l

Answer 10

2 ester groups and 1 tertiary amine group

Question 11

What functional group in cocaine makes it a base?

https://pubchem.ncbi.nlm.nih.gov/image/imgsrv.fcgi?cid=446220&t=l

Answer 11

The tertiary amine

Question 12

What is the SAR strategy of cutting open a benzene ring?

Answer 12

Simplification

Question 13

Which bond is more resistant to hydrolysis, amide or esters?

Answer 13

Amide

Amide tends to be much more stable and, as a result, more resistant to hydrolysis

Question 14

What is semi-synthetic method?

Answer 14

A semi-synthetic compound:
- A semi-synthetic product is made from a natural product and modifying it with a few more steps

Question 15

What is the difference between semi-synthetic and synthetic drug?

Answer 15

Semi-synthetic drug starts with a natural product.

Synthetic drug is made from scratch.