PharmacologyTier 1Medical Sciences concept

Ion trapping and urinary pH manipulation in drug elimination (weak acids/bases)

Core concept

Only the non-ionised, lipid-soluble form of a weak acid/base crosses membranes; the ionised form is "trapped" in whichever compartment favours ionisation
Weak acids ionise in alkaline environments; weak bases ionise in acidic environments (Henderson-Hasselbalch)
Manipulating urine pH shifts the ionisation of a weak acid/base drug in the renal tubule -> traps it in urine -> increases elimination

Alkalinise urine (e.g. IV sodium bicarbonate) to enhance elimination of weak acids: classic example salicylate (aspirin) overdose
- Alkaline urine -> salicylate ionises -> cannot be reabsorbed across tubular membrane -> trapped -> excreted
Acidify urine to trap weak bases -- rarely used clinically now (risk of myoglobin precipitation/renal injury in rhabdomyolysis-prone overdoses e.g. amphetamines) -- largely historical for exam purposes
Same ion-trapping principle explains why urine pH affects excretion of methotrexate (weak acid, alkalinisation used to prevent crystallisation/toxicity) and phenobarbital (weak acid)

Urinary alkalinisation is first-line enhanced elimination in significant salicylate toxicity (target urine pH ~7.5-8), alongside standard supportive care and consideration of haemodialysis in severe cases
Trap: forced diuresis alone (without alkalinisation) does not meaningfully enhance salicylate elimination -- the pH shift, not urine flow rate, is the active mechanism
Systemic alkalosis from bicarbonate therapy must be monitored (over-alkalinisation, hypokalaemia which paradoxically impairs urinary alkalinisation via renal K-H exchange)

Same weak acid/base principle explains placental and CNS drug trapping in fetal acidosis (weak bases like local anaesthetics ion-trap in the more acidic fetal compartment)
Methotrexate alkalinisation (prevent renal tubular crystallisation) is a related but distinct rationale from salicylate elimination enhancement
Contrast with haemodialysis, used for severe salicylate toxicity when alkalinisation alone is insufficient (severe acidosis, renal failure, very high levels, CNS effects)

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