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Pharmacology · Pharmacokinetics: ion trapping
Sample itemA 20-year-old woman is brought in after ingesting a large number of aspirin tablets. She has tinnitus, rapid breathing and a mixed acid-base disturbance. Aspirin is a weak acid with a pKa of about 3.5. Why does alkalinising the urine with intravenous sodium bicarbonate hasten salicylate elimination?
Original practice item, not a recalled exam question. Nothing here is recorded.
The answer and the reasoning
C. Salicylate becomes more ionised in tubular fluid, so it cannot be passively reabsorbed
Only the non-ionised fraction of a weak electrolyte crosses the tubular epithelium. For a weak acid, raising the pH of tubular fluid above its pKa shifts it to the ionised form, which is trapped in the lumen and excreted. This ion trapping is the basis of urinary alkalinisation in salicylate and phenobarbitone poisoning.
Option by option
A. Salicylate becomes more lipid soluble, so it is secreted more actively into the tubule
Ionisation reduces, not increases, lipid solubility, and passive back-diffusion is what is being prevented.
B. Glomerular filtration of salicylate rises because alkalinisation dilates the afferent arteriole
Filtration depends on size and protein binding, not on urinary pH.
C. Salicylate becomes more ionised in tubular fluid, so it cannot be passively reabsorbed (correct)
Correct. Ionised salicylate is polar and is trapped in alkaline urine.
D. Hepatic glucuronidation of salicylate is accelerated by the higher urinary pH
Hepatic metabolism is unrelated to urinary pH, which acts only after the drug has been filtered.
Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.
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