Test your medicinal chemistry: drug-likeness (Lipinski’s rule of five), prodrugs, bioisosteres, chirality, drug metabolism, ionization and the mechanisms of common drug classes. There are 15 questions. Click an answer to see whether you are right, with a short explanation.
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1.Under Lipinski's rule of five, an orally active drug should generally have a molecular weight of not more than:
Answer: B. Lipinski's rule of five: molecular weight ≤ 500 Da, log P ≤ 5, no more than 5 hydrogen-bond donors and no more than 10 hydrogen-bond acceptors. Poor absorption is more likely when more than one rule is broken.
2.Under Lipinski's rule of five, the maximum number of hydrogen-bond donors is:
Answer: B. No more than 5 hydrogen-bond donors (OH and NH groups) and no more than 10 hydrogen-bond acceptors (N and O atoms).
3.Which of these ACE inhibitors is an ester prodrug?
Answer: D. Enalapril is an ethyl ester that is hydrolysed in the liver to the active diacid enalaprilat. The ester improves oral absorption. Captopril and lisinopril are active as given; atenolol is a beta-blocker.
4.Codeine is converted to morphine by O-demethylation mainly through:
Answer: D. CYP2D6 converts codeine to morphine. Poor metabolisers get little analgesia, and ultra-rapid metabolisers are at risk of morphine toxicity.
5.In losartan, the tetrazole ring acts as a bioisostere of which group?
Answer: C. The tetrazole ring has a similar acidity (pKa about 4.5–4.9) and planar shape to a carboxylic acid but is more lipophilic and metabolically stable.
6.Giving only the (R)-enantiomer of thalidomide would not prevent its teratogenic effect because:
Answer: A. Thalidomide racemizes rapidly under physiological conditions, so a single enantiomer quickly becomes a mixture of both.
7.Beta-lactam antibiotics such as penicillins kill bacteria by:
Answer: C. The strained beta-lactam ring acylates the active-site serine of the transpeptidases that cross-link peptidoglycan, weakening the cell wall.
8.Clavulanic acid is combined with amoxicillin because it:
Answer: D. Clavulanic acid is a beta-lactamase inhibitor with weak antibacterial activity of its own. It protects amoxicillin from hydrolysis by beta-lactamase-producing bacteria.
9.Which of these is a Phase II (conjugation) metabolic reaction?
Answer: C. Phase II reactions attach a polar group: glucuronidation, sulfation, acetylation, methylation and glutathione or amino acid conjugation. Oxidation, reduction and hydrolysis are Phase I reactions.
10.Aspirin inhibits cyclooxygenase (COX) by:
Answer: B. Aspirin transfers its acetyl group to a serine in COX, inactivating it for the life of the enzyme. In platelets, which cannot make new COX, the effect lasts for the platelet's lifespan.
11.Log P is a measure of a drug's:
Answer: A. Log P is the logarithm of the octanol/water partition coefficient of the un-ionized form. Log D accounts for ionization at a given pH.
12.Sulfonamide antibacterials work by competitively inhibiting:
Answer: A. Sulfonamides are structural analogues of p-aminobenzoic acid (PABA) and inhibit dihydropteroate synthase in bacterial folate synthesis. Trimethoprim inhibits dihydrofolate reductase.
13.Aspirin (pKa about 3.5) in the stomach (pH about 1.5) exists mainly in which form?
Answer: D. For a weak acid, when pH is 2 units below the pKa, about 99% is un-ionized (Henderson–Hasselbalch), which favours absorption across membranes. Calculations quiz →
14.Lidocaine has a longer duration of action than procaine mainly because lidocaine:
Answer: D. Procaine is an ester and is rapidly hydrolysed by plasma cholinesterase. Lidocaine is an amide that is metabolised more slowly in the liver.
15.Carbidopa is given with levodopa to:
Answer: C. Carbidopa does not cross the blood-brain barrier. It blocks conversion of levodopa to dopamine outside the brain, so more levodopa reaches the CNS and peripheral side effects such as nausea are reduced.