FPGEE Pharmaceutical Chemistry 4 — Questions and Answers
Question 1: Hydrolytic degradation of aspirin in aqueous solution produces:
- Acetaminophen and acetic acid
- Salicylic acid and acetic acid (Correct answer)
- Salicylamide and acetaldehyde
- Phenol and carbonic acid
Correct answer: Salicylic acid and acetic acid
The ester bond in aspirin (acetylsalicylic acid) is hydrolyzed to yield salicylic acid and acetic acid in aqueous conditions.
Question 2: In drug-receptor binding, the term 'affinity' refers to:
- The maximum pharmacological effect a drug can produce
- The strength of the drug-receptor interaction (Correct answer)
- The rate at which a drug is eliminated
- The selectivity of a drug for one receptor subtype over another
Correct answer: The strength of the drug-receptor interaction
Affinity describes how strongly a drug binds to its receptor, often expressed as the dissociation constant (Kd).
Question 3: What is the primary purpose of determining the pKa of a drug molecule?
- To predict its metabolic pathway
- To predict ionization state at physiological pH affecting absorption and distribution (Correct answer)
- To determine its molecular weight
- To assess photostability
Correct answer: To predict ionization state at physiological pH affecting absorption and distribution
pKa determines the degree of drug ionization at any given pH, which critically influences membrane permeability, absorption, distribution, and renal excretion.
Question 4: Which structural feature makes beta-lactam antibiotics susceptible to bacterial resistance via beta-lactamase enzymes?
- The amide side chain
- The strained four-membered lactam ring (Correct answer)
- The thiazolidine ring system
- The carboxylic acid group
Correct answer: The strained four-membered lactam ring
Beta-lactamase enzymes hydrolyze the strained beta-lactam ring, which is essential for antibacterial activity, rendering the antibiotic inactive.
Question 5: The concept of 'hard acid-hard base' and 'soft acid-soft base' interactions (HSAB theory) in medicinal chemistry is most relevant to:
- Predicting drug solubility in GI tract
- Understanding metal-ligand interactions in metal-based drugs (Correct answer)
- Calculating drug partition coefficients
- Determining drug protein binding rates
Correct answer: Understanding metal-ligand interactions in metal-based drugs
HSAB theory explains the selectivity of metal-based drugs (e.g., cisplatin) for particular biological ligands like DNA nitrogen atoms versus sulfur-containing proteins.
Question 6: Racemization of a chiral drug during storage is a significant concern because:
- It increases the drug's aqueous solubility
- It may alter the ratio of active to inactive (or toxic) enantiomers (Correct answer)
- It always increases drug potency
- It prevents Phase I metabolism
Correct answer: It may alter the ratio of active to inactive (or toxic) enantiomers
If enantiomers have different activity or toxicity profiles, racemization changes the effective dose of the active isomer and may increase adverse effects.
Question 7: Thalidomide's teratogenicity is primarily associated with which pharmacological concept?
- Drug-drug interaction via CYP inhibition
- Stereoisomer toxicity — the S-enantiomer causes birth defects (Correct answer)
- Prodrug activation failure
- Crystalline polymorphism altering absorption
Correct answer: Stereoisomer toxicity — the S-enantiomer causes birth defects
The S-(-)-enantiomer of thalidomide is teratogenic while the R-(+)-enantiomer has sedative activity; however, interconversion between enantiomers occurs in vivo.
FPGEE Pharmaceutical Chemistry 4
Hydrolytic degradation of aspirin in aqueous solution produces: