In acid-base balance and renal handling of drugs, urinary alkalinization (raising urine pH) increases the renal elimination of which substance?

• A. Morphine (predominantly a weak base)
• B. Phenobarbital (a weak acid)
• C. Amphetamine (a weak base)
• D. Ethanol (neutral molecule)

Answer: (B)

Verified step by step guidance

1. Step 1: Understand the concept of renal elimination and how urine pH affects the excretion of weak acids and weak bases. The kidneys eliminate substances by filtration, secretion, and reabsorption, and the degree of ionization of a drug influences its reabsorption in the renal tubules.
2. Step 2: Recall that weak acids and weak bases exist in equilibrium between their ionized and non-ionized forms, which depends on the pH of the environment. The Henderson-Hasselbalch equation describes this relationship:
3. \[ \text{pH} = \text{p}K_a + \log \left( \frac{[\text{A}^-]}{[\text{HA}]} \right) \]
4. where \([\text{A}^-]\) is the ionized (charged) form and \([\text{HA}]\) is the non-ionized (uncharged) form of the weak acid.
5. Step 3: Recognize that ionized forms of drugs are less lipid-soluble and therefore less likely to be reabsorbed in the renal tubules, leading to increased elimination in urine. Conversely, non-ionized forms are more lipid-soluble and more likely to be reabsorbed.
6. Step 4: Apply this knowledge to urinary alkalinization (raising urine pH). For weak acids, increasing urine pH shifts the equilibrium toward the ionized form, increasing their elimination. For weak bases, increasing urine pH shifts the equilibrium toward the non-ionized form, decreasing their elimination.
7. Step 5: Conclude that urinary alkalinization increases the renal elimination of weak acids (like phenobarbital) but decreases the elimination of weak bases (like morphine and amphetamine), while neutral molecules like ethanol are not significantly affected.