Stability of drugs Flashcards
Ester containing drugs undergo slow hydrolysis under ______ conditions
neutral
Hydrolysis can be catalysed by ____ or _____
acid
base
Aspirin hydrolyses to _______ and ________
salicylic acid
ethanoic acid
What are the storage conditions for ester containing drugs?
Airtight container to prevent access to moisture
Amides and carbamates are more susceptible to hydrolysis than esters. True or false?
False
Hydrolysis of an ester results in an alcohol and a carboxylic acid. True or false?
True
The first step in acid-catalysed hydrolysis of esters is a substitution. True or false?
False - it is an addition step - the nucleophile is added (water)
The second step of an acid catalysed hydrolysis is elimination (of ethanol) followed by elimination of proton True or false?
True
In base catalysed hydrolysis of esters the first step is addition of electrophile. True or false?
False - addition of nucleophile
The overall mechanism for base catalysed hydrolysis of esters is substitution. True or false?
True - first step is addition, second step is elimination
What makes the C=O if an amide less susceptible to attack by nucleophiles?
Resonance
Why is the 4-membered cyclic amide in Penicillins prone to hydrolysis?
Steric strain in the ring
Why do penicillins need to be stored in the fridge?
Susceptible to hydrolysis
Radicals can form from OH, NH and CHs. True or false?
True
Free radical oxidation is a problem for phenolic drugs especially the catechol group. True or false?
True
FRO is a problem for aromatic amines and unsaturated aliphatic compounds. True or false?
True
The process of FRO is more rapid at low pH. True or false?
False - rapid at high pH
Which hormone contains a catechol group formulated as the tartaric acid salt to keep it acidic (and minimise FRO)?
Adrenaline
Absorption of energy can promote the electrons in a bond to an ‘excited state’ generating ______
radicals
How do you prevent light from forming FRO in medicines?
Store medicines in foil packaging or brown bottles
Transition metals can accept an _______ and initiate radical formation
electron
How do you prevent metals from forming FR?
Add a metal chelating agent e.g. EDTA
Fe3+ + e- -> ____
Fe2+
In the presence of light, oxygen forms ________ radicals that give rise to oxidation and degradation of medicines
peroxide
How do you prevent FR formation from oxygen?
Store medicines in a well filled, well closed container
Add another gas e.g. Nitrogen
How do antioxidants prevent radical formation?
They trap radicals, preventing their self-propagation.
They mop up radicals or form stabilised radicals that do not continue the chain
BHT, Vitamin E, Vitamin C are e.g.s of ?
antioxidants
