A 64-year-old woman with CKD stage 4 has serum calcium 8.4 mg/dL, phosphate 6.2 mg/dL, and PTH 720 pg/mL. She is intolerant of calcitriol because of recurrent hypercalcaemia. Cinacalcet is added to her regimen. By what mechanism does this drug lower PTH?
- A It acts as a positive allosteric modulator of the calcium-sensing receptor on parathyroid cells ✓
- B It chelates intestinal phosphate and reduces the stimulus for parathyroid growth
- C It binds the vitamin D receptor and suppresses PTH gene transcription
- D It blocks preosteoclast RANK ligand activation in bone
Correct answer: A. It acts as a positive allosteric modulator of the calcium-sensing receptor on parathyroid cells
Explanation
Cinacalcet is a calcimimetic that binds allosterically to the seven-transmembrane calcium-sensing receptor on parathyroid chief cells, increasing the receptor's sensitivity to ambient ionised calcium. The gland therefore perceives the calcium level as higher than it is and secretes less PTH. It differs from calcitriol analogues, which act on the vitamin D receptor, and from phosphate binders, which work in the gut lumen. Denosumab targets RANKL in bone and has no direct parathyroid effect. Cinacalcet can cause hypocalcaemia, so monitoring is needed.
Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.
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