L32B - Molecular (chemical) Basis For Drug Degredation

Question 1

What does much of the synthesis require?

Answer 1

Reactive functional groups

Question 2

What are examples of reactive functional groups?

Answer 2

• acid chloride and aldelhyde
• alkyl halide
• a,b unsaturated carbonyls (michael acceptors)

Question 3

What are is drug degredation usually because?

Answer 3

• photolytic degradation
• hydrolysis

Question 4

What is the general principle for photolytic degradation?

Answer 4

Molecule absorbs a photon (IR, visible or UV light) causing the molecule to go from ground to excited state and can then spontaneously decompose or react

Question 5

What is the photodegredation of chloramphenicol?

Answer 5

Oxidation of the benzylic carbon
- benzylic carbons are more reactive than standard alkyl groups

Question 6

What are various corticosteroid and antimycotics susceptible to?

Answer 6

Photodecomposition

Question 7

What does photodecomposition affect for pharmacists? And for pharmacologists?

Answer 7

Pharmacist - formulation, storage, etc.
Pharmacologist - stability of stock solutions, reliability of combinatorial libraries etc.

Question 8

What is photolytic degradation as a negative?

Answer 8

Degrades some medicines and could produce toxic products

Question 9

How is photolytic degradation avoided?

Answer 9

• amber bottles
• blister packs
• storage of sensitive drugs in the fridge

Question 10

What is the main issue probably with with photolytic degredation?

Answer 10

Extemporaneously prepared solutions

Question 11

What do alternatives solutions use to prevent photolytic degredation?

Answer 11

• addative that is able to competitively absorb light
• adding physical quencher

Question 12

What is a quencher?

Answer 12

Compound that causes physical decay of the excited state before decomposition occurs

Question 13

What is photolytic degredation as a positive?

Answer 13

Can be used to reduce the effect of pharmaceuticals on the environment

Question 14

What happens to medicines prescribed that are lost? How are they eliminated?

Answer 14

• end up in the waste water system - significant effect on the environment
• photo-assisted wastewater treatment methods used to eliminate them

Question 15

What is the take home messafe for photolytic degredation?

Answer 15

• can be complex with multiple pathways (radical chem)
• involves oxidation (+ benzylic oxidation)

Question 16

What is hydrolytic degradation?

Question 17

What do you do to minimise hydrolysis of the strained lactam rin of pediatric penicillin suspension?

Answer 17

Aq suspension, needs to bre prepared immediatly before dispensing
- kept in the refrigerator

Question 18

What are not suited to continuous infusion due to reactivity?

Answer 18

Many beta-lactam drugs

Question 19

What are biologics like? + degredation?

Answer 19

• largelt protein-based
• increasingly gene and cellular or carbohydrate based
• degradation/modification of peptide backbones and side chains

Question 20

What are potential problems of biologics?

Answer 20

• large size and complicated structure
• hydrolysis of backbone
• oxidation of susceptible side chains

Question 21

What are examples of oxidation of susceptible side chains?

Answer 21

• 2 Cys residues oxidised to form a dishulphibe bond = protein aggregation
• ox of methionine to methionine sulfoxide R-SMe -> R-S(O)Me

Question 22

What is an example of a substance susceptible to photodecomposition? (2)

Answer 22

Natamycin (antifungal)
- typical dosage forms are a cream and eye drops
- can degrade by up to 50% over 30 min when exposed to light after they are applied

Question 23

What is susceptible to hydrolytic degradation?

Answer 23

• ester
• amide
• lactone
• lactam