Pharmacy Pharmaceutical Chemistry 4 — Questions and Answers
Question 1: Which metabolic pathway is responsible for the conversion of codeine to morphine in the body?
- N-demethylation by CYP3A4
- O-demethylation by CYP2D6 (Correct answer)
- Glucuronidation by UGT enzymes
- Sulfation by SULT enzymes
Correct answer: O-demethylation by CYP2D6
CYP2D6 catalyzes O-demethylation of codeine at the 3-methoxy position, converting it to the more pharmacologically active morphine.
Question 2: The Maillard reaction in pharmaceutical formulations refers to:
- Oxidation of unsaturated lipids
- Non-enzymatic browning reaction between reducing sugars and amines (Correct answer)
- Hydrolysis of ester bonds in a formulation
- Photodegradation of active ingredients
Correct answer: Non-enzymatic browning reaction between reducing sugars and amines
The Maillard reaction is a non-enzymatic condensation between reducing sugars (excipients like lactose) and primary amines in drug molecules, causing discoloration and potency loss.
Question 3: Which property of a drug is described by its logP value?
- Aqueous solubility
- Lipophilicity (partition between octanol and water) (Correct answer)
- Ionization at physiological pH
- Protein binding affinity
Correct answer: Lipophilicity (partition between octanol and water)
LogP (octanol-water partition coefficient) quantifies lipophilicity; a higher logP indicates greater lipid solubility and typically better membrane permeability.
Question 4: Sulfonamide antibiotics act by competitively inhibiting the bacterial enzyme that uses which substrate?
- Para-aminobenzoic acid (PABA) (Correct answer)
- Dihydrofolate
- Glutamic acid
- Pteridine
Correct answer: Para-aminobenzoic acid (PABA)
Sulfonamides structurally mimic PABA and competitively inhibit dihydropteroate synthase, blocking bacterial folate synthesis.
Question 5: In NMR spectroscopy, the chemical shift (δ) of a proton is primarily influenced by:
- The molecular weight of the compound
- The electron density around the proton (shielding/deshielding) (Correct answer)
- The melting point of the compound
- The solubility of the compound in the NMR solvent
Correct answer: The electron density around the proton (shielding/deshielding)
Electron-withdrawing groups deshield nearby protons (downfield shift, higher δ) while electron-donating groups increase shielding (upfield shift, lower δ).
Question 6: What is the significance of the 'rule of five' (Lipinski's rule) in drug design?
- A drug must have exactly 5 chiral centers for biological activity
- Predicts whether a compound will have good oral bioavailability based on MW, logP, H-bond donors, and acceptors (Correct answer)
- A drug must be metabolized by exactly 5 enzymes
- A drug needs 5 different functional groups to be pharmacologically active
Correct answer: Predicts whether a compound will have good oral bioavailability based on MW, logP, H-bond donors, and acceptors
Lipinski's rule of five states that orally bioavailable drugs typically have MW ≤500, logP ≤5, ≤5 H-bond donors, and ≤10 H-bond acceptors.
Question 7: Warfarin exerts its anticoagulant effect by inhibiting:
- Thrombin directly
- Vitamin K epoxide reductase, preventing regeneration of active Vitamin K (Correct answer)
- Platelet aggregation via COX-1 inhibition
- Factor Xa in the coagulation cascade
Correct answer: Vitamin K epoxide reductase, preventing regeneration of active Vitamin K
Warfarin inhibits vitamin K epoxide reductase (VKOR), depleting reduced vitamin K needed as a cofactor for synthesis of clotting factors II, VII, IX, and X.
Pharmacy Pharmaceutical Chemistry 4
Which metabolic pathway is responsible for the conversion of codeine to morphine in the body?