Pharmacology · Cytotoxic and Targeted Therapy (Monoclonal Antibodies)

A patient receiving cetuximab for head and neck cancer develops hypomagnesemia. Which mechanism explains this electrolyte abnormality?

  • A Cetuximab causes renal magnesium wasting via direct tubular toxicity
  • B Cetuximab chelates magnesium in the gastrointestinal lumen, reducing absorption
  • C EGFR is expressed in the distal convoluted tubule where it facilitates magnesium reabsorption; EGFR blockade impairs this
  • D EGFR inhibition causes secondary hyperaldosteronism, increasing renal magnesium excretion
Correct answer: C. EGFR is expressed in the distal convoluted tubule where it facilitates magnesium reabsorption; EGFR blockade impairs this

Explanation

EGFR is expressed in the distal convoluted tubule and collecting duct, where it activates the TRPM6 magnesium channel essential for renal magnesium reabsorption. EGFR inhibition by cetuximab or panitumumab impairs this pathway, causing renal magnesium wasting and hypomagnesemia. This is a class effect of EGFR inhibitors, not chelation or aldosterone-mediated.

Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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