Structure-activity relationships and drug metabolism

30 Gulf Prometric Pharmacist (DHA, DOH, MOH, SCFHS, QCHP) practice questions on Structure-activity relationships and drug metabolism, part of Pharmacology and Medicinal Chemistry. The first 25 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

1. Question 1 · Easy

   Which structural feature of penicillins is cleaved by beta-lactamase enzymes?

   1. AThe beta-lactam ring
   2. BThe carboxylate group
   3. CThe phenyl side chain
   4. DThe thiazolidine ring

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   Answer: A · The beta-lactam ring

   Penicillins consist of a beta-lactam ring fused to a thiazolidine ring. The strained four-membered beta-lactam ring acylates the transpeptidase, and bacterial beta-lactamases hydrolyse that ring to give inactive penicilloic acid. Beta-lactamase inhibitors such as clavulanic acid protect it.

   • B: The carboxylate is needed for binding but is not cleaved.
   • C: The side chain affects spectrum and acid stability but is not cleaved.
   • D: The thiazolidine ring is not the site of beta-lactamase attack.

   Remember this

   Beta-lactamases hydrolyse the beta-lactam ring and inactivate the penicillin.

2. Question 2 · Easy

   In the stomach at pH 1.5, aspirin (a weak acid, pKa 3.5) is best described as:

   1. AMostly un-ionised and readily absorbed
   2. BAlmost completely ionised and poorly absorbed
   3. CConverted to salicylate and ionised
   4. DHalf ionised and half un-ionised

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   Answer: A · Mostly un-ionised and readily absorbed

   A weak acid is mostly un-ionised when the pH is below its pKa. At pH 1.5, aspirin is more than 99% un-ionised, and the lipid-soluble form crosses membranes easily. The pH-partition rule explains why acidic drugs are absorbed in the stomach, although the small intestine's large surface still provides most absorption.

   • B: Ionisation would dominate only at pH well above 3.5.
   • C: Hydrolysis is slow in gastric acid and does not set ionisation.
   • D: Half ionisation occurs at pH equal to the pKa, which is 3.5.

   Remember this

   Weak acids are un-ionised at pH below their pKa; weak bases are un-ionised at pH above their pKa.

3. Question 3 · Medium

   Why is penicillin V more stable in gastric acid than penicillin G?

   1. AIts beta-lactam ring is larger and therefore less strained
   2. BIt carries a second, protective beta-lactam ring in the side chain
   3. CIts electron-withdrawing side-chain oxygen reduces carbonyl participation
   4. DIt is much more lipid soluble and so is absorbed before it degrades

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   Answer: C · Its electron-withdrawing side-chain oxygen reduces carbonyl participation

   In acid, the side-chain carbonyl oxygen of penicillin G attacks the beta-lactam carbonyl and opens the ring. The phenoxy oxygen of penicillin V withdraws electrons and reduces this participation, so the drug survives gastric acid and can be given orally.

   • A: The beta-lactam ring size is the same in both.
   • B: Penicillin V has only one beta-lactam ring.
   • D: Lipid solubility does not explain the acid stability.

   Remember this

   An electron-withdrawing group in the acyl side chain gives acid-stable oral penicillins.

4. Question 4 · Medium

   A patient with a pseudocholinesterase variant receives suxamethonium for intubation and stays paralysed for hours. Why does this happen?

   1. AReduced renal clearance of unchanged suxamethonium
   2. BSlow hepatic glucuronidation of the drug and its metabolites
   3. CRapid redistribution of the drug into body fat stores
   4. DReduced plasma ester hydrolysis prolongs the block

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   Answer: D · Reduced plasma ester hydrolysis prolongs the block

   Suxamethonium is a diester that plasma butyrylcholinesterase hydrolyses within minutes, which is why its action is short. An atypical or deficient enzyme leaves much of the dose unhydrolysed and the paralysis lasts for hours. Treatment is ventilation and sedation until recovery.

   • A: Suxamethonium is cleared by esterase, not by the kidney.
   • B: Glucuronidation is not its metabolic route.
   • C: Redistribution is not the cause of prolonged paralysis.

   Remember this

   Atypical plasma cholinesterase causes prolonged suxamethonium paralysis.

5. Question 5 · Medium

   Why does lidocaine have a longer duration of action than procaine?

   1. AIts amide bond resists hydrolysis by plasma esterases
   2. BIt is not metabolised by the liver
   3. CIt is more highly ionised at physiological pH
   4. DIt has a lower lipid solubility

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   Answer: A · Its amide bond resists hydrolysis by plasma esterases

   Procaine is an ester and is hydrolysed within minutes by plasma pseudocholinesterase. Lidocaine has an amide link, which is stable in plasma and metabolised slowly by hepatic CYP enzymes, so its action lasts longer.

   • B: Lidocaine is cleared mainly by hepatic metabolism.
   • C: More ionisation would slow entry to the nerve and not prolong action.
   • D: Lower lipid solubility would shorten rather than prolong action.

   Remember this

   Ester local anaesthetics are hydrolysed by plasma esterases; amide types are cleared by the liver.

6. Question 6 · Medium

   Which structural feature is essential for the antibacterial activity of sulfonamides?

   1. AA tertiary amine group on the aromatic ring
   2. BA free aromatic amino group para to the sulfonamide
   3. CA carboxylic acid group at position 3 of the ring
   4. DAn ester group on the sulfonamide nitrogen atom

   Answer and explanation in LearnFree account

7. Question 7 · Easy

   Which enzyme family transfers glucuronic acid to drugs in phase II metabolism?

   1. AGlutathione S-transferases
   2. BCytochrome P450 monooxygenases
   3. CUDP-glucuronosyltransferases
   4. DN-acetyltransferases

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8. Question 8 · Hard

   A weak acid has a pKa of 3.4. In intestinal fluid at pH 6.4, approximately what fraction of the drug is un-ionised?

   1. A50%
   2. B1%
   3. C10%
   4. D0.1%

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9. Question 9 · Medium

   A man takes ciprofloxacin with a calcium-containing antacid and his infection does not respond. Which structural feature of ciprofloxacin explains the interaction?

   1. AThe cyclopropyl group at N-1, which raises potency
   2. BThe piperazine ring at position 7, which widens the spectrum
   3. CThe fluorine at position 6, which raises gyrase binding
   4. DThe 3-carboxylic acid and 4-keto groups chelating metal ions

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10. Question 10 · Medium

    A patient with advanced renal failure given morphine becomes deeply sedated and has respiratory depression. Which metabolite accumulates?

    1. AMorphine-6-glucuronide
    2. BMorphine-3-glucuronide only
    3. CCodeine
    4. DNormorphine only

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11. Question 11 · Medium

    A patient with tuberculosis who is a slow acetylator takes isoniazid and develops numbness and tingling in the feet. Which statement best explains this?

    1. AFast glucuronidation produces a neurotoxic metabolite
    2. BSlow acetylation raises isoniazid levels and depletes pyridoxine
    3. CRifampicin blocks the N-acetyltransferase enzyme
    4. DIsoniazid is converted to a toxic product by CYP2D6

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12. Question 12 · Medium

    Which drug's renal excretion is increased by alkalinising the urine in overdose?

    1. APethidine
    2. BQuinidine
    3. CAmphetamine
    4. DSalicylate

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13. Question 13 · Easy

    Which of the following ACE inhibitors is a prodrug that must be hydrolysed to its active diacid form?

    1. AEnalaprilat
    2. BEnalapril
    3. CLisinopril
    4. DCaptopril

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14. Question 14 · Hard

    Valaciclovir gives a higher bioavailability of aciclovir (about 55%) than oral aciclovir (about 15-30%). What is the main reason?

    1. AIt is converted to aciclovir in the stomach
    2. BIt avoids first-pass metabolism by lymphatic uptake
    3. CIt is more lipophilic and crosses membranes by passive diffusion
    4. DA valine ester prodrug taken up by PEPT1 and hydrolysed to aciclovir

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15. Question 15 · Medium

    A patient is given racemic ibuprofen. Which statement about its enantiomers is correct?

    1. AThe S-enantiomer is the only one absorbed from the gut
    2. BOnly S-ibuprofen inhibits COX, and R is partly converted to S in vivo
    3. CBoth enantiomers inhibit COX equally and neither is inverted
    4. DOnly the R-enantiomer inhibits COX and it is not inverted

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16. Question 16 · Easy

    Hydroxylation of a drug by cytochrome P450 is classified as which type of metabolism?

    1. APhase III transport
    2. BPhase I functionalisation
    3. CPhase 0 uptake
    4. DPhase II conjugation

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17. Question 17 · Hard

    A patient with both severe hepatic and renal failure needs a neuromuscular blocker in intensive care. Which is the best choice and why?

    1. APancuronium, because it is metabolised by esterases
    2. BVecuronium, because it is cleared mainly by the liver
    3. CCisatracurium, because Hofmann elimination is organ independent
    4. DRocuronium, because it is cleared entirely by the kidney

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18. Question 18 · Medium

    According to Lipinski's rule of five, which property predicts poor oral absorption?

    1. AA log P below 1
    2. BFewer than 5 hydrogen-bond donors
    3. CMolecular mass over 500 daltons
    4. DMolecular mass under 300 daltons

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19. Question 19 · Medium

    Which antiplatelet drug acts without needing metabolic activation?

    1. APrasugrel
    2. BClopidogrel
    3. CTicagrelor
    4. DTiclopidine

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20. Question 20 · Medium

    In losartan, the biphenyl tetrazole ring serves as a bioisostere of which group?

    1. AA carboxylic acid
    2. BAn ester
    3. CA phenol
    4. DA primary amine

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21. Question 21 · Hard

    A patient with chronic kidney disease takes allopurinol and the dose is reduced because of a long-lived metabolite. Which statement is correct?

    1. AOxypurinol is the active metabolite and accumulates as renal function falls
    2. BUric acid is the active metabolite and accumulates
    3. CAllopurinol is inactive and oxypurinol is cleared by the liver
    4. DXanthine is the active metabolite cleared by the kidney

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22. Question 22 · Easy

    Esomeprazole is best described as which form of omeprazole?

    1. AThe racemic mixture
    2. BAn active metabolite
    3. CThe R-enantiomer
    4. DThe S-enantiomer

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23. Question 23 · Medium

    Remifentanil wears off within minutes even after a long infusion, and its offset is unchanged in liver or kidney failure. Which feature explains this?

    1. AIts ester group is hydrolysed by blood and tissue esterases
    2. BIt is excreted unchanged by glomerular filtration
    3. CIt redistributes rapidly from the brain into fat
    4. DIt is glucuronidated in the liver to inactive products

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24. Question 24 · Medium

    In paracetamol overdose, which metabolite binds to hepatocyte proteins and causes centrilobular necrosis?

    1. Ap-Aminophenol from deacetylation
    2. BParacetamol glucuronide conjugate
    3. CN-acetyl-p-benzoquinone imine
    4. DParacetamol sulfate conjugate

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25. Question 25 · Medium

    Why is levodopa, rather than dopamine, given to treat Parkinson disease?

    1. ALevodopa crosses the blood-brain barrier on an amino acid carrier
    2. BLevodopa binds dopamine receptors directly in the striatum
    3. CLevodopa is not metabolised at all in the peripheral tissues
    4. DDopamine is not synthesised in the brain, so it must be supplied

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