Pharmaceutical Sciences and Drug Chemistry
Core concepts
The exam expects you to connect molecular structure to behaviour in the body. Know the acid–base definitions (Arrhenius, Brønsted–Lowry, Lewis), the Henderson–Hasselbalch relationship, and how pKa determines the ionised fraction at physiological pH. Understand functional groups - carboxylic acids, amines, amides, esters, phenols - and the reactions they undergo (hydrolysis, oxidation, salt formation). Stereochemistry matters: enantiomers differ in receptor affinity and metabolic fate, and questions often hinge on distinguishing enantiomers from diastereomers. Solubility, partition coefficient (log P), and hydrogen bonding explain absorption and distribution. Know the concepts of prodrugs, bioisosteres, and structure–activity relationships. Drug stability chemistry (hydrolytic, oxidative, photolytic degradation) links directly to later domains on storage and expiry.
Traps in questions
- Confusing the ionised and unionised fractions: weak acids are more unionised (and better absorbed) in acidic gastric fluid.
- Assuming all isomers are mirror images; geometric (cis/trans) isomers are diastereomers, not enantiomers.
- Treating log P as a measure of water solubility rather than lipophilicity.
- Forgetting that salt forms change solubility and stability but not the intrinsic activity of the parent molecule.
Worked example / rule of thumb
For a weak acid with pKa 4.4 in plasma at pH 7.4, the ratio of ionised to unionised is 10^(7.4−4.4) = 10^3, so roughly 99.9% is ionised and trapped in plasma - a classic "ion trapping" question. Rule of thumb: when pH equals pKa, the ionised and unionised forms are equal; each pH unit above pKa shifts a weak acid's ratio tenfold toward the ionised form.