L32- molecular basis for drug degradation

what type of functional groups are usually avoided in drugs and why

functional groups that act as electrophiles/ that react with nucleophiles

e.g. acid chlorides, aldehyde alpha-beta unsaturated carbonyls

as the body is full of nucleophiles especially on enzymes and proteins this reaction can be toxic and cause a change in their conformation

what reactions/ mechanisms cause and a re involved in the degradation of drugs

• hydrolysis

• photolytic degradation

explain what photolytic degradation is

• its typically oxidation- typically benzylic oxidation

• molecules absorb photons from uv, ir or visible and it causes the molecule to go from ground state to excites causing it to spontaneously react/ degrade

• drugs that are susceptible to this degradation can still be used but things such as packaging and storage need to considered

• its easy to control but the main issue is with extemporaneously prepared solutions

what are ways to avoid photolytic degradation

• amber bottle

• blister packs

• storage in the fridge

• you can also add additives that can absorb the light

what is the effect of repackaging medication in a dosset box for example

• removing medication from its original packaging can often invalidate the stability guarantee of the manufacturer

• a pharmacist must ensure that they make informed judgement regarding this

describe the degradation of biologicals

• as they are largely protein based the main concern is when they are denatured- when they are unfolded or misfolded their biological function may change or wont be carried out at all

• it can happen through: oxidation of susceptible side chains like cys,met ( formation of disulphide bond or addition of oxygen )or hydrolysis of the backbone